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1.
  • Hollén, Elisabet, et al. (author)
  • Antibodies to oat prolamines (avenins) in children with coeliac disease
  • 2003
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 38:7, s. 742-746
  • Journal article (peer-reviewed)abstract
    • Background: The use of oats in a gluten-free diet for children with coeliac disease is presently under investigation. In this study we measured the content of antibodies to oat prolamines (avenin) in sera from coeliac children and reference children. Methods: Crude avenin was prepared by extraction with ethanol and salt-solution and used as antigen in a three-step ELISA. Sera from 81 children, including 34 children with verified coeliac disease, were analysed for both IgA and IgG antibodies to avenin and gliadin. Sera were also incubated with gliadin before exposure to avenin, and vice versa, to assess a possible cross-reaction between the species. Keyhole limpet hemocyanin (KLH) was used as a negative control. Results: Children with coeliac disease on a normal diet had significantly higher levels of antibodies to avenin, both IgG and IgA, than reference children ( P < 0.001) and the levels correlated positively with gliadin antibodies, especially of IgA-type ( r = 0.798). Both anti-avenin and anti-gliadin antibodies were only absorbed by the corresponding protein. Conclusions: Children with coeliac disease have antibodies to oat proteins at significantly higher levels than reference children. The absorption test did not indicate a cross-reactivity between the prolamines of wheat and oats. The method will be employed for repeated sampling of anti-avenin antibodies during a prospective interventional study with a gluten-free diet supplemented with oats.
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2.
  • Hollén, Elisabet, et al. (author)
  • Coeliac children on a gluten-free diet with or without oats display equal anti-avenin antibody titres
  • 2006
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:1, s. 42-47
  • Journal article (peer-reviewed)abstract
    • Objective. Recent studies report negligible toxicity of oats in the majority of coeliac disease (CD) patients. It has previously been shown that children with untreated CD have circulating antibodies to oats avenin. In this study we performed serial assessments of anti-avenin antibodies in children under investigation for CD on a gluten-free diet with or without oats. Material and methods. The study involved 116 children, randomized to a standard gluten-free diet or a gluten-free diet supplemented with oats. Sera were obtained from 86 children, 48 in the standard gluten-free group and 38 in the gluten-free oats group, of which 33 consumed at least 10 g of oats daily. IgA and IgG anti-avenin antibodies were monitored at 0, 3, 6 and 12 months. Nitric oxide metabolites were measured in 7 patients, with deviating antibody results. Results. There was a significant decrease in anti-avenin antibodies in both groups at the end as compared to the beginning of the study, (p<0.001), but no difference was found between the two groups. IgA titres already declined after 3 months. IgG titres, although significantly decreased, remained high in the majority of patients in both groups. Nitric oxide levels were high in four of the analysed samples. Conclusions. Oats per se, do not seem to produce a humoral immune reaction in children with CD when given in an otherwise gluten-free diet, indicating that the reaction requires gluten challenge. Anti-avenin antibodies were equal in the two study groups, and these findings strengthen the clinical impression that oats can be tolerated by the majority of patients with CD.
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3.
  • Hollén, Elisabet, et al. (author)
  • Urinary nitric oxide during one year of gluten-free diet with or without oats in children with coeliac disease
  • 2006
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:11, s. 1272-1278
  • Journal article (peer-reviewed)abstract
    • Objective. Although in both adults and children with coeliac disease (CD) it is now recommended that oats be added to their gluten-free diet, there is still some controversy concerning the possible harmful effects of oats in some individuals. In this study concentrations of nitric oxide metabolites were repeatedly measured in the urine of children under investigation for CD, when on a gluten-free diet with or without oats. Material and methods. The study included 116 children, randomized to a standard gluten-free diet (GFD-std) or a gluten-free diet supplemented with wheat-free oat products (GFD-oats), over a one-year period. Small-bowel biopsy was performed at the beginning and end of the study. Morning urine samples were collected from 87 children and urinary nitrite/nitrate concentrations were monitored at 0, 3, 6, 9 and 12 months. Results. All patients were in clinical remission after the study period. There was a rapid decline in urinary nitrite/nitrate concentrations in both groups as early as after 3 months. No differences were seen between the study groups at any of the checkpoints. However, at the end of the study, the nitrite/nitrate values of 9 children in the GFD-oats group and 8 children in the GFD-std group had not normalized. Conclusions. Children with CD on a gluten-free diet with oats display a similar reduction in urinary nitrite/nitrate as those on a traditional gluten-free diet. Some children, however, still demonstrate high nitrite/nitrate excretion after one year on either diet, indicating that long-term follow-up studies of children on an oats-containing diet are needed.
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4.
  • Högberg, Lotta, et al. (author)
  • Children with screening-detected coeliac disease show increased levels of nitric oxide products in urine
  • 2011
  • In: ACTA PAEDIATRICA. - : Blackwell Publishing Ltd. - 0803-5253 .- 1651-2227. ; 100:7, s. 1023-1027
  • Journal article (peer-reviewed)abstract
    • Aim: Increased concentration of nitric oxide (NO) metabolites, nitrite and nitrate, in the urine is a strong indication of ongoing small intestinal inflammation, which is a hallmark of the enteropathy of coeliac disease (CD). It has previously been shown that children with symptomatic, untreated CD have increased levels of NO oxidation products in their urine. The aim of this study was to investigate whether screening-detected, asymptomatic coeliac children display the same urinary nitrite/nitrate pattern. Methods: In a multicenter screening study, serum samples were collected from 7208 12-year-old children without previously diagnosed CD. Sera were analysed for anti-human tissue transglutaminase (tTG) of isotype IgA. Small bowel biopsy was performed in antibody-positive children, yielding 153 new cases of CD. In the screening-detected individuals, the sum of nitrite and nitrate concentrations in the urine was analysed and used as an indicator of NO production. For comparison, 73 children with untreated, symptomatic CD were studied. Results: The nitrite/nitrate levels in children with screening-detected CD and those with untreated symptomatic CD did not differ significantly. Both groups had significantly increased urinary nitrite/nitrate concentrations compared to the children with normal small bowel biopsy (p andlt; 0.001). Conclusion: Children with screening-detected CD have increased production of NO just as children with untreated symptomatic CD. High NO metabolite levels in the urine may indicate a pathogenetic feature of CD and be a marker of major clinical importance.
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5.
  • Kivling, Anna, et al. (author)
  • Diverging immune responses when allergy, type 1 diabetes and celiac disease coexist
  • Other publication (other academic/artistic)abstract
    • An imbalance between different immune cells, among them T-cells and inflammatory cells, has been proposed to be part of the disease process in type 1 diabetes (T1D), celiac disease and allergy. T-cells and inflammatory cells exert their actions through cytokines and chemokines, and the secretion of those can be used to describe the cell milieu during an immune response. This study included seventy-two children, diagnosed with T1D, celiac disease, allergy, or a combination of two of these diseases and compared to reference children. The study aimed to evaluate the secretion of 27 different cytokines and chemokines in cell culture supernatant after in vitro stimulation with disease-associated antigens (birch, gluten, insulin) detected by Luminex technique. Combination of allergy with either T1D or celiac disease gave diverging results. Children with combination of T1D and allergy showed an increased secretion of several cytokines (IL-2, IL-4, IL-5, IL-7, IL-9, IL-10, IL-12, IL-15, IL-17 and CCL11), in comparison to almost all groups from birch stimulation. In contrast, when allergy was combined with celiac disease, the spontaneous secretion of IL-1β, IL-5, IL-6, IL-9, IL-10, IL-12 and CCL3 was decreased compared to children with T1D or allergy, as well as children with celiac disease alone, children with combination of T1D and allergy and reference children. In conclusion, our results shed some light on the immune responses in children with common immunological diseases. Our study indicates diverging immune responses when allergy, type 1 diabetes and celiac disease coexist.
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7.
  • Sjöberg, Veronika, et al. (author)
  • Noncontaminated dietary oats may hamper normalization of the intestinal immune status in childhood celiac disease
  • 2014
  • In: Clinical and Translational Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 2155-384X. ; 5
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: Life-long, strict gluten-free diet (GFD) is the only treatment for celiac disease (CD). Because there is still uncertainty regarding the safety of oats for CD patients, the aim was to investigate whether dietary oats influence the immune status of their intestinal mucosa.METHODS: Paired small intestinal biopsies, before and after >11 months on a GFD, were collected from children with CD who were enrolled in a randomized, double-blind intervention trial to either of two diets: standard GFD (GFD-std; n=13) and noncontaminated oat-containing GFD (GFD-oats; n=15). Expression levels of mRNAs for 22 different immune effector molecules and tight junction proteins were determined by quantitative reverse transcriptase (RT)-PCR.RESULTS: The number of mRNAs that remained elevated was higher in the GFD-oats group (P=0.05). In particular, mRNAs for the regulatory T cell (Treg) signature molecules interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1), the cytotoxicity-activating natural killer (NK) receptors KLRC2/NKG2C and KLRC3/NKG2E, and the tight junction protein claudin-4 remained elevated. Between the two groups, most significant differences were seen for claudin-4 (P=0.003) and KLRC3/NKG2E (P=0.04).CONCLUSIONS: A substantial fraction of pediatric CD patients seem to not tolerate oats. In these patients, dietary oats influence the immune status of the intestinal mucosa with an mRNA profile suggesting presence of activated cytotoxic lymphocytes and Tregs and a stressed epithelium with affected tight junctions. Assessment of changes in levels of mRNA for claudin-4 and KLC3/NKG2E from onset to after a year on oats containing GFD shows promise to identify these CD patients.
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9.
  • Sundqvist, Tommy, et al. (author)
  • Significantly increased levels of nitric oxide products in urine of children with celiac disease
  • 1998
  • In: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Ovid Technologies (Wolters Kluwer Health). - 0277-2116 .- 1536-4801. ; 27:2, s. 196-198
  • Journal article (peer-reviewed)abstract
    • Background: Celiac disease is characterized by morphologic and functional aberrations of the small intestinal mucosa, i.e. crypt hyperplasia, villous atrophy, infiltration of intraepithelial lymphocytes, and alteration of permeability. Nitric oxide has been shown to affect mucosal permeability after ischemia-reperfusion, but little is known about the regulatory role of nitric oxide in celiac disease. The purpose of this study was to assess nitric oxide production in children with celiac disease and in control subjects.Methods: The sum of nitrite and nitrate in the urine was measured with a colorimetric method in 137 children with a median age of 3 years, 84 patients and 53 reference children, all of whom underwent a small intestinal biopsy to confirm or overrule suspicion of celiac disease.Results: Median urinary nitrite-nitrate concentration in celiac children was 3323µM (4147 ± 1102; mean ± SEM) at first clinical examination and 2501 µM (2939 ± 386) after gluten challenge, which was significantly higher than concentrations in reference children(1029 µM; 1174 ± 116) and in children with celiac disease on a gluten-free diet (882 µM; 1369 ± 360) (p< 0.0001).Conclusions: A gluten-containing diet is associated with an increased nitrite-nitrate secretion in the urine in children with celiac disease, presumably as a result of nitric oxide synthase activation and nitric oxide production in the diseased small intestinal mucosa.
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10.
  • Tjellstrom, B., et al. (author)
  • The effects of oats on the function of gut microflora in children with coeliac disease
  • 2014
  • In: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 39:10, s. 1156-1160
  • Journal article (peer-reviewed)abstract
    • Background Faecal short chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported high faecal SCFA levels in children with coeliac disease (CD), indicating alteration in gut microfloral metabolism. Data accumulated over recent decades by us and others suggest that wheat-free oats can safely be included in a gluten-free diet (GFD). However, concerns have been raised with respect to the safety of oats in a subset of coeliacs. Aim To describe faecal SCFA patterns in children with newly diagnosed CD treated for 1year with a GFD with or without oats. Methods This report is part of a randomised, double-blind study on the effect of a GFD containing oats (GFD-oats) vs. a standard GFD (GFD-std). Faecal samples were received from 34 children in the GFD-oats group and 37 in the GFD-std group at initial diagnosis and/or after 1year on a GFD. Faecal SCFAs were analysed. Results The GFD-std group had a significantly lower total faecal SCFA concentration at 12months compared with 0months (Pless than0.05). In contrast, total SCFA in the GFD-oats group remained high after 1year on the GFD. The children in the GFD-oats group had significantly higher acetic acid (Pless than0.05), n-butyric acid (Pless than0.05) and total SCFA concentration (Pless than0.01) after 1-year diet treatment compared to the GFD-std group. Conclusions Our results indicate that oats do affect the gut microflora function, and that some coeliac children receiving oats may develop gut mucosal inflammation, that may present a risk for future complications.
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11.
  • Tjellström, Bo, et al. (author)
  • Faecal short-chain fatty acid pattern in childhood coeliac disease is normalised after more than one year's gluten-free diet
  • 2013
  • In: Microbiological Ecology in Health and Disease. - Järfälla, Sweden : Co-Action Publishing. - 0891-060X .- 1651-2235. ; 24
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Recent work indicates that the gut microflora is altered in patients with coeliac disease (CD). Faecal short-chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported a high SCFA output in children with symptomatic and asymptomatic CD at presentation, as well as in CD children on a gluten-free diet (GFD) for less than 1 year, indicating deviant gut microfloral function. In this report, we focus on faecal SCFA production in coeliacs on GFD for more than 1 year.MATERIALS AND METHODS: Faecal samples were collected from 53 children with CD at presentation, 74 coeliac children on GFD for less than 1 year, and 25 individuals diagnosed with CD in childhood and on GFD for more than 1 year. The control group comprised 54 healthy children (HC). The faecal samples were analysed to show the SCFA pattern taken as a marker of gut microflora function. We applied a new fermentation index, reflecting the inflammatory activity of the SCFAs (amount of acetic acid minus propionic acid and n-butyric acid, together divided by the total amount of SCFAs).RESULTS: In coeliacs on GFD for more than 1 year, the individual SCFAs, total SCFA, and fermentation index did not differ significantly from the findings in controls. In contrast, the faecal SCFA level was clearly higher in coeliacs treated with GFD for less than 1 year compared to those more than 1 year.CONCLUSIONS: This is the first study on SCFA patterns in faecal samples from individuals with CD on GFD for more than 1 year. Our study indicates that the disturbed gut microflora function in children with CD at presentation and after less than 1 year of GFD, previously demonstrated by us, is normalised on GFD for more than 1 year.
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12.
  • Tjellström, Bo, et al. (author)
  • Gut microflora associated characteristics in children with celiac disease
  • 2005
  • In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 100:12, s. 2784-2788
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: The aim of the study was to investigate the metabolic function of intestinal microflora in children with celiac disease (CD) in order to find out if there is a deviant gut flora in CD patients compared to healthy controls. METHODS: The study group comprised children with CD, consecutively diagnosed according to current criteria given by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition. Thirty-six children were studied at presentation, i.e., on a normal gluten-containing diet, with clinical symptoms and signs indicative of CD, positive celiac serology markers, and a small bowel biopsy showing severe enteropathy. Forty-seven patients were studied when they had been on a gluten-free diet (GFD) for at least 3 months. For comparison, a group of 42 healthy controls (HC) were studied. The functional status of the intestinal microflora was evaluated by gas-liquid chromatography of short chain fatty acids (SCFAs) in fecal samples. RESULTS: There was a significant difference between untreated CD children and HC as well as between treated CD children and HC regarding acetic, i-butyric, i-valeric acid, and total SCFAs. The propionic and n-valeric acids differed significantly between CD children on GFD and HC. Moreover, there was a strong correlation between i-butyric and i-valeric acids in all study groups. CONCLUSIONS: This is the first study of the SCFA pattern in fecal samples from children with CD. The results indicate that there is a difference in the metabolic activity of intestinal microbial flora in children with CD compared to that in HC. The finding of a different pattern of some SCFAs in celiacs both at presentation and during treatment with GFD indicates that it is a genuine phenomenon of CD not affected by either the diet, the inflammation, or the autoimmune status of the patient. © 2005 by Am. Coll. of Gastroenterology Published by Blackwell Publishing.
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13.
  • Tjellström, Bo, et al. (author)
  • Gut microflora associated characteristics in first-degree relatives of children with celiac disease
  • 2007
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 42:10, s. 1204-1208
  • Journal article (peer-reviewed)abstract
    • Objective. In celiac disease (CD), enteropathy of the small bowel results from a T-cell-mediated reaction to gluten in the diet. In addition to gluten, other environmental and genetic factors participate in the disease pathogenesis. We have recently reported the finding of a significantly different short-chain fatty acid (SCFA) profile in fecal samples from children with CD compared to healthy controls reflecting an aberrant gut microflora. The aim of the present study was to make a functional evaluation of the gut microflora status in non-celiac 1st degree relatives of children with CD. Material and methods. Fecal samples from 76 symptom-free, non-celiac, 1st degree CD relatives and from 91 aged-matched healthy controls were analyzed for fecal tryptic activity (FTA) and a number of SCFAs. Results. There was a significantly lower level of acetic acid and total SCFAs as well as a significantly increased level of i-butyric acid and FTA in relatives compared to healthy controls. Conclusions. The FTA and the SCFA profiles in fecal samples from 1st degree relatives of children with CD are different from those of healthy individuals. The implication of this observation provides insight into the pathogenesis of CD and opens up the possibility of future new diagnostic, therapeutic and prophylactic strategies. © 2007 Taylor & Francis.
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14.
  • Tjellström, Bo, et al. (author)
  • Screening-detected and symptomatic untreated celiac children show similar gut microflora-associated characteristics
  • 2010
  • In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 45:9, s. 1059-1062
  • Journal article (peer-reviewed)abstract
    • Objective. The aim of this study was to investigate the metabolic function of intestinal microflora in children with screening-detected celiac disease (CD) to see if there is an aberrant gut flora in screening-detected CD similar to symptomatic CD and contrary to healthy controls. Materials and methods. As part of a Swedish multicenter screening for CD, 912 12-year-old children were screened with serum anti-human tissue transglutaminase-IgA. Small bowel biopsy specimens from children with positive serology revealed 17 individuals with CD. The functional status of the intestinal microflora was evaluated by gas liquid chromatography of short chain fatty acids (SCFAs) in fecal samples. Our previously published findings in children with symptomatic CD and healthy controls were used as comparison. Results. The children with screening-detected CD had a similar fecal SCFA profile to children with symptomatic CD, but differed significantly from that in healthy children. Conclusions. This is the first study on SCFA patterns in fecal samples from children with screening-detected CD. The similarity of the fecal SCFA profile in screening-detected and symptomatic CD indicates common pathogenic mechanisms. This could open the way for new therapeutic or prophylactic measures based on novel biological principles.
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16.
  • Byström, IngMarie, et al. (author)
  • Health-Related Quality of Life in Children and Adolescents with Celiac Disease: From the Perspectives of Children and Parents
  • 2012
  • In: Gastroenterology Research and Practice. - : Hindawi Publishing Corporation. - 1687-6121 .- 1687-630X. ; 2012
  • Journal article (peer-reviewed)abstract
    • Aim. To examine how celiac children and adolescents on gluten-free diet valued their health-related quality of life, and if age and severity of the disease at onset affected the childrens self-valuation later in life. We also assessed the parents valuation of their childs quality of life. Methods. The DISABKIDS Chronic generic measure, short versions for both children and parents, was used on 160 families with celiac disease. A paediatric gastroenterologist classified manifestations of the disease at onset retrospectively. Results. Age or sex did not influence the outcome. Children diagnosed before the age of five scored higher than children diagnosed later. Children diagnosed more than eight years ago scored higher than more recently diagnosed children, and children who had the classical symptoms of the disease at onset scored higher than those who had atypical symptoms or were asymptomatic. The parents valuated their childrens quality of life as lower than the children did. Conclusion. Health-related quality of life in treated celiac children and adolescents was influenced by age at diagnosis, disease severity at onset, and years on gluten-free diet. The disagreement between child-parent valuations highlights the importance of letting the children themselves be heard about their perceived quality of life.
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17.
  • Cederborg, Ann-Christin, 1952-, et al. (author)
  • Living with children who have coeliac disease: a parental perspective
  • 2012
  • In: Child Care Health and Development. - : Blackwell Publishing. - 0305-1862 .- 1365-2214. ; 38:4, s. 484-489
  • Journal article (peer-reviewed)abstract
    • Background This study explores how a childs coeliac disease (CD) influences the daily life of families because such knowledge can enhance the understanding of how to support family adjustment to a gluten-free diet (GFD). Methods We used an interpretative phenomenological approach, interviewing 20 parents of 14 children diagnosed with CD about their individual thoughts and beliefs. Results Once parents know, especially when their children are young, they seem to have the capacity to rapidly adapt to GFD, mainly because they notice how quickly their children recover. Parents may have problems controlling how staff at daycare and at school complies with their information about a GFD. Conclusions To ensure that children with CD are given a GFD at daycare and school, it is necessary for municipalities to educate staff about the disease and to give them the prerequisites for serving a GFD. There is also a need of early identification of children who may have CD. When parents express their worries, not just at the hospital but also at the well-baby clinic and primary care units, supporting treatment could prevent children from suffering from inappropriate food.
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18.
  • Devenney, Irene, et al. (author)
  • A new model for low-dose food challenge in children with allergy to milk or egg.
  • 2006
  • In: Acta Paediatr. - : Wiley. - 0803-5253 .- 1651-2227. ; 95:9, s. 1133-9
  • Journal article (peer-reviewed)abstract
    • Division of Paediatrics, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, and Paediatric Clinic, County Hospital Ryhov, Fonköping, Sweden. irene.devenney@lio.seBACKGROUND: Atopic eczema and food allergy are common in early childhood. Children seem to gradually develop tolerance to milk and egg, and it is a relief for families when their child can tolerate small amounts of these basic foods, even if larger doses may still cause symptoms. AIM: To develop a model for low-dose oral food challenge, facilitating re-/introduction of milk or egg. METHODS: In 39 children sensitized to milk and/or egg, we performed 52 challenges using a new standardized model for low-dose oral food challenge. The recipes were validated for blinding with sensorial tests. RESULTS: Four children challenged to milk had a positive challenge outcome. There were no significant differences with respect to family history, associated atopic manifestations, nutritional supply, eczema severity, or skin-prick test compared with the non-reacting children, but total and specific IgE values were significantly higher. All but two of the non-reacting children were able to introduce milk and egg into their diet without problems. CONCLUSION: We report recipes and a protocol to be used for standardized open and double-blind placebo-controlled low-dose food challenge in young children, enabling the introduction of small amounts of egg and milk into the diet during tolerance development.
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19.
  • Devenney, Irene, 1959- (author)
  • Assessing eczema and food allergy in young children
  • 2006
  • Doctoral thesis (other academic/artistic)abstract
    • Background: Atopic disease is an increasing problem. Eczema affects 10-20% of young children, and 33-37% of children with eczema are food allergic. Among other factors, nitric oxide (NO) is thought to play a role in eczema and food allergy. Following the atopic march, pproximately 80% of children with atopic eczema will become sensitized to aeroallergens and develop asthma and/or allergic rhinitis. Skin prick test is used for investigating sensitization and is considered a safe method. However, systemic allergic reactions may appear when the test is performed. In diagnosing food allergy and for evaluating achievement of tolerance, the oral food challenge is the method of choice, and the double-blind placebocontrolled fashion is 'the gold standard'.Skin prick test: We examined six cases of generalized allergic reactions in connection with skin prick testing in order to identify risk factors, and thereby increase safety, and we investigated the necessity of performing skin prick tests in duplicate. We found that all six children with generalized reactions were <6 months of age. When analyzing skin prick tests in duplicate, we found only 1.3% that showed diverging results, and in infants <6 months even fewer, 0.9%.Food challenge: We developed recipes and a protocol for low-dose oral food challenge to milk and egg to be used in young children outgrowing their food allergy so as to facilitate early re-/introduction of small amounts of milk and egg. We performed 52 challenges, both open and double-blind placebo controlled. The recipes were validated for blinding. The lowdose challenge was tolerated well by the children and was easy to perform. Four children had a positive challenge outcome, all reacting to very small amounts of milk. All but two of the non-reacting children were able to introduce milk and egg into their diet.Nitric oxide and eczema: We investigated the effect of eczema treatment on the NO levels in urine. The sum of nitrite and nitrate was measured in urinary samples from 94 infants at two visits, with an interval of 6 weeks, and the results were compared with clinical data. The levels of NO products increased significantly when the eczema improved.The atopic march: The aim was to evaluate the atopic march in children with eczema, from referral at <2 years until 4½ years of age. We followed 123 children with eczema, 78 sensitized and 45 not sensitized to milk and/or egg, with respect to eczema severity, other allergic manifestations, development of airway sensitization, and achievement of food tolerance. The difference in severity of eczema at referral was significant when comparing food-sensitized with non-sensitized children. At follow-up, 62% were still affected by eczema, although 56% only mildly so. Tolerance was achieved in 81% of the children allergic to milk and 68% of those allergic to egg. Fifty-eight percent of the food-sensitized children and 26% of the non-sensitized children had become sensitized to aeroallergens, a significant difference. The difference in airway symptoms was not significant. Very few children were exposed to tobacco smoke in their homes.Conclusions: Increased precautions should be considered when performing skin prick tests in infants <6 months of age. The use of a single prick, to avoid the risk of summation of reactions, is justified when performing skin prick tests. We report recipes and a protocol for standardized open and double-blind placebo-controlled low-dose food challenge in young children, enabling the introduction of small amounts of egg and milk into the diet during tolerance development. NO products in urine increases when eczema improves. This might be due to a Th2/Th1 shift induced by the eczema treatment and skin healing, and the variation in NO response may be due to individual variations in NO-induced feedback downregulation of Th1 and Th2 proliferation. The prognosis for achieving clinical tolerance is very good in children early sensitized and allergic to milk and egg, but they will become significantly more often sensitized to aeroallergens.
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21.
  • Devenney, Irene, et al. (author)
  • Skin prick test in duplicate : is it necessary?
  • 2001
  • In: Annals of Allergy, Asthma & Immunology. - 1081-1206. ; 87:5, s. 386-389
  • Journal article (peer-reviewed)abstract
    • Background: Duplicate skin prick testing has previously been recommended because of reports that accidental negative tests are common. However, duplicate tests also mean an extra allergen load, which may increase the risk of inducing a generalized reaction at the test situation, at least in the youngest infants. Objective: To investigate whether the occurrence of both a positive and negative test result is a common feature when performing duplicate skin prick tests and can therefore justify the duplicate method. Methods: A retrospective analysis of all skin prick tests performed in duplicate at the pediatric clinic at University Hospital in Linköping, Sweden, in 1997. Results: Of 1,087 skin prick tests, 14 resulted in one positive and one negative test, or 1.3%. The corresponding figure in the youngest age group, (ie, <2 years of age) was 3 of 340 (0.9%). Conclusions: Considering the risk of inducing a summation of the reactions, and thereby a generalized allergic reaction, when applying an extra allergen load on the limited surface of the small arm, we conclude that the results of this study justify using single prick test, at least in the youngest age group and probably when testing children of all ages.
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22.
  • Devenney, Irene, et al. (author)
  • Skin prick tests may give generalized allergic reactions in infants
  • 2000
  • In: Annals of Allergy, Asthma & Immunology. - 1081-1206. ; 85:6, s. 457-460
  • Journal article (peer-reviewed)abstract
    • Background: Skin prick testing, a widely used method of studying sensitization, is usually considered quick, pedagogic, and relatively inexpensive. Previous studies have shown very few negative reactions and no fatalities. In contrast, both anaphylaxis and death have been reported as a result of intracutaneous tests. Objective: To examine detailed case studies of generalized allergic reactions in connection with skin prick testing in order to identify possible risk factors and thereby increase the safety of the test procedure. Method: A retrospective study of medical records of six cases with generalized allergic reaction occurring during the study period 1996-1998 at the Pediatric Clinic, University Hospital of Linköping, Sweden. Data about the total number of children tested during the period were collected from the clinic's database. Results: All six cases with generalized reactions were infants <6 months who showed positive skin prick tests to fresh food specimen. Other common features were active eczema and a family history of allergic disease. All infants received prompt treatment and recovered well. The overall rate of generalized reactions was 521 per 100,000 tested children. In the age group <6 months, the corresponding figure was 6522 per 100,000. Conclusion: The risk of generalized reactions after skin prick test with fresh food specimens in young children ought to be acknowledged and should lead to increased precautions when performing the test.
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23.
  • Devenney, Irene, et al. (author)
  • Urinary nitric oxide excretion in infants with eczema
  • 2010
  • In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 21:1, s. e229-e234
  • Journal article (peer-reviewed)abstract
    • Eczema is characterized by inflammation of the skin and is commonly associated with food allergy. It has been suggested that nitric oxide (NO) is an important player in eczema, food allergy and intestinal inflammation. The aim of this study was to assess the levels of urinary NO breakdown products in infants with eczema and the effect of eczema treatment on NO levels. Ninety-four infants with eczema, 58 boys and 36 girls, with a mean age of 7.5 ± 5.2 months (mean ± s.d.) at inclusion were examined twice with an interval of 6 wk. The sum of nitrite and nitrate was measured colorimetrically in urinary samples from both visits and compared with clinical data concerning eczema severity, nutrition, gastrointestinal symptoms, asthma and skin prick positivity. The levels of NO products increased significantly from the first to the second visit: 289; 374 μm (median; IQR) vs. 457; 678 μm (median; IQR) (p < 0.001) in parallel with a significant improvement of the eczema. After eczema treatment consisting of skin care and elimination diet during the 6-wk interval between evaluations, the NO levels approached the values previously found in healthy children. The results support previous studies indicating that the homeostasis of nitrogen radicals is disturbed in childhood eczema.
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24.
  • Ekbäck, Marie, et al. (author)
  • Severe Eczema in Infancy Can Predict Asthma Development. A Prospective Study to the Age of 10 Years
  • 2014
  • In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:6, s. e99609-
  • Journal article (peer-reviewed)abstract
    • Background: Children with atopic eczema in infancy often develop allergic rhinoconjunctivitis and asthma, but the term "atopic march has been questioned as the relations between atopic disorders seem more complicated than one condition progressing into another. Objective: In this prospective multicenter study we followed children with eczema from infancy to the age of 10 years focusing on sensitization to allergens, severity of eczema and development of allergic airway symptoms at 4.5 and 10 years of age. Methods: On inclusion, 123 children were examined. Hanifin-Rajka criteria and SCORAD index were used to describe the eczema. Episodes of wheezing were registered, skin prick tests and IgE tests were conducted and questionnaires were filled out. Procedures were repeated at 4.5 and 10 years of age with additional examinations for ARC and asthma. Results: 94 out of 123 completed the entire study. High SCORAD points on inclusion were correlated with the risk of developing ARC, (B = 9.86, P = 0.01) and asthma, (B = 10.17, P = 0.01). For infants with eczema and wheezing at the first visit, the OR for developing asthma was 4.05(P = 0.01). ARC at 4.5 years of age resulted in an OR of 11.28(P = 0.00) for asthma development at 10 years. Conclusion: This study indicates that infant eczema with high SCORAD points is associated with an increased risk of asthma at 10 years of age. Children with eczema and wheezing episodes during infancy are more likely to develop asthma than are infants with eczema alone. Eczema in infancy combined with early onset of ARC seems to indicate a more severe allergic disease, which often leads to asthma development. The progression from eczema in infancy to ARC at an early age and asthma later in childhood shown in this study supports the relevance of the term "atopic march, at least in more severe allergic disease.
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25.
  • Friedman, William J, et al. (author)
  • Childrens Memory for the Duration of a Paediatric Consultation
  • 2010
  • In: APPLIED COGNITIVE PSYCHOLOGY. - : John Wiley and Sons, Ltd. - 0888-4080 .- 1099-0720. ; 24:4, s. 545-556
  • Journal article (peer-reviewed)abstract
    • To learn about childrens ability to estimate the duration of an event many days after it occurred, 6-12-year-old children were asked to judge the amount of time (range 5-45 minutes) they spent in the treatment room as part of a paediatric visit. Judgements were made 1 week or 1 month after the visit occurred. Children showed an average error of about 13 minutes. Retention interval did not significantly affect estimates. Other judgements of the length of the interview itself (mean length 8 minutes) provided what may be the first data on childrens ability to make immediate retrospective duration estimates. The results also include information about childrens capacity to judge how long ago they visited the clinic.
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26.
  • Furuhjelm, Catrin, et al. (author)
  • Allergic disease in infants up to 2 yr of age in relation to plasma omega-3 fatty acids and maternal fish oil supplementation inpregnancy and lactation
  • 2011
  • In: Pediatric Allergy and Immunology. - : John Wiley & Sons A/S. - 0905-6157 .- 1399-3038. ; 22:5, s. 505-514
  • Journal article (peer-reviewed)abstract
    • We have previously reported a protective effect of maternal omega-3 long-chain polyunsaturated fatty acids (x-3 LCPUFA) supplementation in pregnancy and lactation on IgE-associated eczema and food allergy in the infant during the first year of life. Here we investigate whether the effects of the LCPUFA supplementation on IgE-associated diseases last up to 2 yr of age and assess the relationship between plasma proportions of x-3 PUFAs and the frequency and severity of infant allergic disease. 145 pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid (EPA) and 1.1 g docosahexaenoic acid (DHA) or placebo starting in the 25th gestational week and continuing through 3.5 months of breastfeeding. Clinical examinations, skin prick tests and analysis of maternal and infant plasma phospholipid fatty acids and infant specific IgE were performed. No difference in the prevalence of allergic symptoms was found between the intervention groups. Thecumulative incidence of IgE-associated disease was lower in the x-3-supplemented group (6/54, 13%) compared with the placebo group (19/62, 30%, p = 0.01). Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease (p = 0.01–0.05) in a dose-dependent manner. Higher maternal and infant proportions of DHA and EPA were found if the infants presented none, when compared with multiple allergic symptoms, (p < 0.05) regardless of sensitization. In summary, the x-3 supplementation offered no obvious preventive effect on the prevalence of clinical symptoms of allergic disease, but the decrease in cumulative incidence of IgE-associated disease seen during the first year still remained until 2 yr of age. Furthermore, high proportions of DHA and EPA in maternal and infant plasma phospholipids were associated with less IgE-associated disease and a reduced severity of the allergic phenotype.
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27.
  • Furuhjelm, Catrin (author)
  • Can fish oil in pregnancy and lactation alter maternal and infant immunological responses and prevent allergy in the offspring?
  • 2010
  • Doctoral thesis (other academic/artistic)abstract
    • Background: A connection has been proposed between the increase of allergic disease and the altered composition of fatty acids in the diet in the westernised world. Less oily fish and more vegetable oil are consumed today compared to 50-100 years ago. Programming of the immune responses takes place very early in life and environmental factors, such as fish in the diet, have been suggested to protect from infant allergy.Aim: The general aim of this thesis was to assess the effects of maternal dietary supplementation with ω-3 long chain polyunsaturated fatty acids (LCPUFA), i.e. fish oil, in pregnancy and lactation on the development of allergic symptoms and sensitisation in the infants as well as some immunological markers in mothers and infants.Subjects and methods: This thesis is based on the results from a prospective double-blind placebo-controlled multi-centre trial comprising 145 families. Pregnant women, at risk of having an allergic infant, were recruited at the antenatal clinics and randomised to daily supplementation with 1.6 g eicosapentaenoic acid (EPA, C20:5ω-3) and 1.1 g docosahexaenoic acid (DHA, C22:6ω-3) or placebo, starting in the 25th gestational week and continuing through 3.5 months of breastfeeding. Phospholipid fatty acids in maternal and infant plasma were analysed to assess compliance. Maternal prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and cytokines along with infant vaccine induced responses and chemokines were analysed with ELISA and Luminex techniques. Clinical outcomes were allergic disease and positive skin prick test/detectable circulating IgE antibodies to common allergens.Results: Phospholipid proportions of ω-3 LCPUFA increased significantly in the ω-3 supplemented women and their infants. Lipopolysaccharide-induced PGE2 secretion from whole blood culture supernatants decreased in a majority of the ω-3-supplemented mothers (p<0.01). The decrease in PGE2 production was more pronounced among non-atopic than atopic mothers. No difference in the prevalence of allergic symptoms was found between the intervention groups. The cumulative incidence of IgE associated eczema and IgE mediated food allergy was though reduced in the ω-3 group during the first two years (OR=0.2 and 0.3 compared to placebo, p<0.05 for both). The cumulative incidence of any IgE associated disease during the first two years of life was 13% in the ω-3 supplemented group compared to 30% in the placebo group (p=0.01, OR 0.3, p<0.05). This effect was most evident in infants of non-allergic mothers. Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease (p=0.01-0.05), in a dose dependent manner. In addition, no allergic symptoms as compared to multiple allergic symptoms in the infants, regardless of sensitisation, were related to higher maternal and infant ω-3 LCPUFA status (p<0.05). In infants without, but not with, maternal history of allergy, the ω-3 supplementation was related to lower CC-chemokine ligand 17 (CCL17)/ CXC-chemokine ligand 11 (CXCL11) (Th2/Th1) ratios (p<0.05). Furthermore in non-allergic, but not in allergic infants, ω-3 supplementation was linked with higher Th1-associated CXCL11 levels (p<0.05), as well as increased IgG titres to diphtheria (p=0.01) and tetanus (p=0.05) toxins.Conclusions: A decreased cumulative incidence of IgE associated disease in the infants was found after maternal ω-3 LCPUFA supplementation as well as a reverse dose response relationship between maternal ω-3 LCPUFA status and infant IgE associated disease. Higher plasma proportions of DHA and EPA in were also associated to less severe allergic disease. A tendency towards strengthened Th1 associated response after maternal ω-3 LCPUFA supplementation was indicated in the analysis of maternal and infant immunological markers. These effects, as well as the clinical outcomes, were more pronounced in non-allergic individuals, suggesting gene-by-environment interactions.
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28.
  • Furuhjelm, Catrin, et al. (author)
  • Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy
  • 2009
  • In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 98:9, s. 1461-1467
  • Journal article (peer-reviewed)abstract
    • Maternal intake of omega-3 (-3) polyunsaturated fatty acids (PUFAs) during pregnancy has decreased, possibly contributing to a current increased risk of childhood allergy. Aim: To describe the effects of maternal -3 long-chain PUFA supplementation during pregnancy and lactation on the incidence of allergic disease in infancy. Methods: One hundred and forty-five pregnant women, affected by allergy themselves or having a husband or previous child with allergies, were included in a randomized placebo-controlled trial. Daily maternal supplementation with either 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo was given from the 25(th) gestational week to average 3-4 months of breastfeeding. Skin prick tests, detection of circulating specific immunoglobulin E (IgE) antibodies and clinical examinations of the infants were performed. Results: The period prevalence of food allergy was lower in the -3 group (1/52, 2%) compared to the placebo group (10/65, 15%, p andlt; 0.05) as well as the incidence of IgE-associated eczema (-3 group: 4/52, 8%; placebo group: 15/63, 24%, p andlt; 0.05). Conclusion: Maternal -3 fatty acid supplementation may decrease the risk of food allergy and IgE-associated eczema during the first year of life in infants with a family history of allergic disease.
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29.
  • Furuhjelm, Catrin, et al. (author)
  • Th1 and Th2 chemokines, vaccine induced 1 immunity and allergic disease in infants  after maternal ω-3 fatty acid supplementation during pregnancy and lactation
  • 2011
  • In: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 69:3, s. 259-264
  • Journal article (peer-reviewed)abstract
    • We investigated whether the previously reported preventive effect of maternal ω-3 fatty acid supplementation on IgE-associated allergic disease in infancy may be mediated by facilitating a balanced circulating Th2/Th1 chemokine profile in the infant. Vaccine-induced immune responses at 2 y of age were also evaluated. Pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo from the 25th gestational week through 3.5 mo of breastfeeding. Infant plasma was analyzed for chemokines (cord blood, 3, 12, 24 mo) and anti-tetanus and anti-diphtheria IgG (24 mo). High Th2-associated CC-chemokine ligand 17 (CCL17) levels were associated with infant allergic disease (p < 0.05). In infants without, but not with, maternal history of allergy, the ω-3 supplementation was related to lower CCL17/CXC-chemokine ligand 11 (CXCL11) (Th2/Th1) ratios (p < 0.05). Furthermore, in nonallergic, but not in allergic infants, ω-3 supplementation was linked with higher Th1-associated CXCL11 levels (p < 0.05), as well as increased IgG titers to diphtheria (p = 0.01) and tetanus (p = 0.05) toxins. Thus, the prospect of balancing the infant immune system toward a less Th2-dominated response, by maternal ω-3 fatty acid supplementation, seems to be influenced by allergic status.
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30.
  • Fälth-Magnusson, Karin, et al. (author)
  • Infant feeding history shows distinct differences between Swedish celiac and reference children
  • 1996
  • In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 7:1, s. 1-5
  • Journal article (peer-reviewed)abstract
    • Infant feeding history was investigated in 72 celiac and 288 age-matched reference children in a retrospective questionnaire study. The reply rate was 100% in celiac and 91. 6% in reference children. The celiac children were breast-fed for a significantly shorter time than reference children, and they were less often breast-fed at the introduction of gluten. The age of the children at gluten introduction was similar, but the cellac children were significantly more often introduced by a gluten-containing follow-up formula, while the reference children more often started on a gluten-containing porridge. The results can be interpreted in two ways. First, it could be argued that breast milk per se protects against symptoms of celiac disease in childhood. It could, however, also be claimed that breast-feeding merely modulates the gluten introduction, causing a less abrupt introduction of gluten in the baby diet and thereby fewer overt symptoms of the disease.
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31.
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32.
  • Grodzinsky, Ewa, 1958-, et al. (author)
  • IgA endomysium antibodies : an early predictor for celiac disease in children without villous atrophy
  • 2008
  • In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 97:7, s. 972-976
  • Journal article (peer-reviewed)abstract
    • Aim: To evaluate possible differences between children with anti-endomysium antibodies (EMA) positivity and normal small bowel mucosa and children with positive EMA and an enteropathy diagnosed as celiac disease (CD).Methods: Children with suspected CD and positive EMA (≥1/10) undergoing small bowel biopsy during 1996 to 2002, were investigated (n = 133). Data registered were: year and month of birth, timing of the first biopsy, sex, heredity for CD, dermatitis herpetiformis and diabetes mellitus and outcome of the anti-gliadin antibody test (AGA). The case group, with EMA positivity and normal histology (n = 39; 59% female, mean age at the first biopsy 7.3 years, range 1.4–16), was compared with the disease control group, with positive EMA and a biopsy suggestive and further on diagnosed as CD (n = 94; 56% female; mean age 7.6 years at the first biopsy, range 0.70–17).Results: AGA positivity and heredity for CD were found to predict the outcome of a pathological jejunal mucosa. Nineteen of the 39 children in the case group were rebiopsied of whom 11 had developed an enteropathy during a follow-up period of 2–7 years (median 4.5 years).Conclusions: EMA positivity in the absence of small bowel enteropathy could be a very early predictor for later overt CD, and necessitates further follow-up, especially if the child is AGA positive and there is a family history of CD.
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33.
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34.
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35.
  • Holmberg, Hanna, et al. (author)
  • Induction of diabetes-related autoantibodies below cutoff for "positivity" in young nondiabetic children
  • 2003
  • In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1005, s. 269-274
  • Journal article (peer-reviewed)abstract
    • The aim was to study the natural course of diabetes-related autoantibodies at low concentrations, below "positivity", in a nondiabetic population followed up from infancy. Blood samples were taken from 205 children at 6 weeks, 6 months, 18 months, and 5 years of age. Autoantibodies against GAD65 (GADA), tyrosine phosphatase (IA-2A), and insulin (IAA) were determined by radioligand-binding assays. All children had detectable levels of GADA and approximately half had IA-2A, but only approximately 10% had detectable levels of IAA during the follow-up period. Many children developed IA-2A already at 6 months of age, similar concentrations were seen at 18 months, and then the levels of IA-2A decreased until 5 years of age. GADA were induced less often at 6 months of age, increased up to 18 months, and fluctuated at similar levels up to 5 years of age. IAA were detectable in so few children and at low levels, so no trend in natural course could be revealed. We conclude that there is a natural induction of humoral immune response to β cell autoantigens early in life. Our results suggest that the mechanisms of β cell tolerance to GAD and IA-2 differ in healthy children.
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36.
  • Hultman, Elin (author)
  • Barnperspektiv i barnavårdsutredningar : med barns hälsa och barns upplevelser i fokus
  • 2013
  • Doctoral thesis (other academic/artistic)abstract
    • Avhandlingens övergripande syfte var att fördjupa kunskapen om hur socialtjänsten synliggör barns fysiska och psykiska hälsa samt barns egna upplevelser i barnavårdsutredningar. Resultaten diskuteras utifrån rättsliga förutsättningar samt teorier om barn som subjekt och sociala aktörer. De fyra delstudierna visar att det finns begränsningar i hur hälsan samt barns upplevelser beskrivs om man vill förstå deras behov av stöd. En anledning till detta kan vara att den rättsliga regleringen inte per automatik ger barn status som subjekt och aktörer. Resultaten tyder på att barnperspektivet i både den rättsliga regleringen och genomförandet av barnavårdsutredningar har stärkts jämfört med vad som visats i tidigare forskning men det behövs en utvecklad analys och argumentation kring barns upplevelser och barns hälsa. En sådan förståelse ger förutsättningar för att barn blir synliggjorda utifrån sina unika förutsättningar vilket säkerställer att socialtjänsten tar hänsyn till deras unika behov.
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37.
  • Hultman, Elin, et al. (author)
  • Social workers’ assessments of children’s health when arguing for children’s needs
  • 2015
  • In: Child and Adolescent Social Work Journal. - : Springer US. - 0738-0151 .- 1573-2797. ; 32:4, s. 301-308
  • Journal article (peer-reviewed)abstract
    • In Sweden, child-related social services constitute an institutional body that conducts both preventive and supportive work for children in need of health support. However, in the social services Act (2001:453) there are few concrete statements about how social workers should assess children’s health. In this study we therefore explore how social workers in Sweden adapt to the task of assessing children’s health. Specifically, we investigate the ways in which children’s health is explained in the context of reaching conclusions about the concrete needs of children. Inspired by a social constructionist and discursive analytical approach we analysed 60 written investigations where health concerns were expressed at the point of initiating an investigation. The findings are that social workers limited their assessments of children’s health, using only a few words when mentioning health aspects. There was a difference in how they described physical- and psychological health problems. When they did pay attention to children’s psychological health this was mostly carried out with the use of one single explanation for the cause of the health condition; parental misbehaviour. Besides, this explanation fitted the suggested support. Signs of children’s psychological problems were described by their own destructive behaviour. Physical health was only briefly mentioned and the recommendations for child support involved external assistance. This means that social workers could use a simplified explanatory model lacking descriptions of each child’s life situation. This way of limiting assessment may hinder a deeper understanding of causes and consequences and thereby impose limits on specifying the particular support the child needs.
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38.
  • Hultman, Elin, et al. (author)
  • Vulnerable children's health as described in investigations of reported children
  • 2013
  • In: Child & Family Social Work. - : Wiley-Blackwell. - 1356-7500 .- 1365-2206. ; 18:2, s. 117-128
  • Journal article (peer-reviewed)abstract
    • This study explores whether the social services weigh in health aspects, and what these may be, when investigating reported childrens life situation. Information about physical and psychological health aspects for 259 children in 272 investigations was included. Overall, information about childrens health was limited. Problematic emotions were the most commonly reported health aspect in the investigations, whereas suicidal thoughts, self-harm behaviour and gastrointestinal and renal diseases were mentioned least of all. A cluster analysis revealed that the low level of health information group included the largest sample of data and consisted of investigations with minimal information about childrens health. The three other cluster groups, Neurological diseases and psychosomatic symptoms, Emotional health and Physical and psychological health and destructive behaviour, consisted of investigations conducted mostly according to the model called Childrens Needs In Focus (BBIC, in Swedish, Barns Behov i Centrum). Although these investigations also produced limited information, they provided more than those assessed as having a low level of information about health aspects. The conclusion is that it is necessary to increase information about health aspects in investigations if social welfare systems are to be able to fulfil their ambition of supporting vulnerable childrens need of health care.
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39.
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40.
  • Högberg, Lotta, et al. (author)
  • Familial prevalence of coeliac disease : a twenty-year follow-up study
  • 2003
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 38:1, s. 61-65
  • Journal article (peer-reviewed)abstract
    • BACKGROUND:The genetic predisposition of coeliac disease (CD) is well known. Previous studies of first-degree relatives of coeliac patients have shown that as many as 10% have the disease. In 1981, we published a study in which all first-degree relatives of 32 index patients with CD were investigated by small-bowel biopsy. We found 2 relatives (2%) with CD. The present study is a re-investigation of all first-degree relatives of the same index patients performed 20-25 years after the first study to reveal any new cases of CD in this high-risk population.METHODS:All 120 first-degree relatives were screened for CD by means of serological markers of CD. The relatives with positive markers were submitted to small-bowel biopsy.RESULTS:Eight new cases of CD were found among the relatives. Two had been investigated by small-bowel biopsy 20 years previously, when they had only minor mucosal changes not classified as CD. The other six new cases of CD were found among offspring of the index patients and were born after completion of the previous study. Thus no new case of CD was found among those relatives who had a completely normal small-bowel biopsy 20-25 years previously.CONCLUSIONS:The high prevalence of CD among first-degree relatives of coeliac patients (8.3% in this study) supports the need to screen for CD in this high-risk population. Even relatives with only mild enteropathy should be followed carefully, since some may subsequently develop CD.
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41.
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42.
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43.
  • Janefjord, Camilla, 1976- (author)
  • Th1, Th2 and Treg associated factors in relation to allergy
  • 2006
  • Doctoral thesis (other academic/artistic)abstract
    • Background: Immune responses are often divided into T helper 1 (Th1), Th2 and Treg like immunity. Allergy is associated with Th2 like responses to allergens and possibly to reduced regulatory functions. Activation via the CD2 receptor increases the production of the Th1 associated cytokine IFN-g and enhances the responses of activated T cells to IL-12. This may be due to an up-regulation of the signal-transducing β2-chain of the IL-12 receptor. CD2 function may be impaired in allergic children. As IL-12 is a strong promoter of Th1 like responses, this may be one contributing factor to the Th2-skewed immune responses found in allergic children. IL-27 and its receptor component WSX-1 may also play a role in Th1 like responses. The transcription factors T-bet, GATA-3 and Foxp3 are associated with Th1, Th2 and Treg type of immune responses, respectively.Aim: To investigate possible mechanisms behind the reduced Th1 and/or Treg associated immunity in relation to allergy by studying the CD2 induced regulation of IL-12Rβ2, WSX-1, T-bet, GATA-3 and Foxp3, as well as the production of different cytokines in children and adults. The aim was also to study the development of these factors during the first two years of life in relation to development of allergy in children from a country with high (Sweden) and low (Estonia) prevalence of allergy.Material and methods: Four different study groups were included; 32 12-year-old children, 38 7-year-old children, 61 children followed from birth to two years of age and 20 adults. Peripheral blood mononuclear cells were cultured with PHA (which partly signals via CD2), IL-2 and IL-12 alone and in combination or with anti-CD2 alone or combined with anti-CD28 antibodies. mRNA expression of cytokine receptors and transcription factors was analysed with real-time PCR and production of Th1, Th2 and Treg associated cytokines with ELISA.Results: We found lower PHA-induced IL-12Rβ2 and IFN-γ production in 12-year-old children with positive skin prick tests (SPT), compared with SPT negative children. We also found lower IL-2 induced IL-12Rβ2 in children with allergic airway symptoms and high IgE levels compared to children without a history of allergy and low IgE levels. This was accompanied with lower IL-2 and IL-12 induced IFN-γ. The spontaneous mRNA expression of IL-12Rβ2, WSX-1, T-bet, GATA-3 and Foxp3 was similar at birth and at 24 months. PHA induced up-regulation of all markers at all ages except for GATA-3, which was up-regulated in allergic children only at 6 and 12 months. PHA-induced T-bet and WSX-1 increased from birth to 24 months in non-allergic children. At a specific age, similar levels of all markers were found in allergic and non-allergic children, except for higher spontaneous IL-12Rβ2 at 24 months and higher PHA-induced WSX-1 at birth in allergic children. All cytokines increased with age. No clear differences were found between Swedish and Estonian children. CD2 stimulation induced Foxp3 and IL-10, while CD2 together with CD28 stimulation induced both Th1 and Th2 related transcription factors and cytokines. The combination also hampered the CD2 induced expression of Foxp3.Conclusions: The CD2 pathway and the response to IL-2 may be impaired in allergic children as lower IL-12Rβ2 and IFN-g were found in allergic, compared to non-allergic children. This difference was not found in adults. CD2 may be involved in induction of regulatory T cell responses as stimulation via CD2 in the absence of other co-stimulatory molecules induced Foxp3 and IL-10. Different developmental patterns of Th1 and Th2 associated factors may influence the development of allergic diseases in childhood.
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44.
  • Karlén, Jerker, 1971-, et al. (author)
  • Are children from Crete abandoning a Mediterranean diet?
  • 2008
  • In: Rural and remote health. - 1445-6354. ; 8:4, s. 1034-
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION:Mediterranean countries such as Greece have experienced rapid social change in the last decade. These community changes affect nutritional habits and there is a tendency for the traditional healthy Mediterranean diet to be abandoned.METHODS:The parents of children from one rural Greek village on Crete (Neapolis), and one rural village in Sweden (Kisa) were invited to their primary health care centers for an interview and to fill in a validated nutrition questionnaire, KidMed.RESULTS:There were no differences (p = 0.48) in total KidMed score between the Cretan and Swedish children, adjusted for gender and age. However, there were some significant differences in scores on certain KidMed questions. Parents of the Cretan children reported significantly higher daily use of olive oil at home and more regular nut consumption, but also more commercially baked goods or pastries for breakfast. The parents of Swedish children reported significantly higher use of cereals, grains or bread for breakfast. The mean BMIs were similar for the Cretan (Neapolis mean 16.8, 95% CI 13.5-23.0) and for the Swedish children (Kisa mean 17.4, 95% CI 13.7-25.5)CONCLUSION:The results suggest the possibility of changing nutritional habits, measurable among young children in rural areas. The study raises the question of whether Cretan children may have abandoned some aspects of the traditional Mediterranean diet. It may also be that Swedish children have changed their diet in favor of a more Mediterranean food choice. The major limitation of the study is the small sample size, and further, larger studies are warranted.
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45.
  • Kivling, Anna, et al. (author)
  • Diverse FOXP3 Expression in Children with Type 1 Diabetes and Celiac Disease
  • 2008
  • In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1150, s. 273-277
  • Journal article (peer-reviewed)abstract
    • Imbalance between different types of T lymphocytes, such as T helper (Th) and regulatory T cells (Tregs), has been reported to play a part in the pathogenesis behind such autoimmune diseases as type 1 diabetes (T1D) and celiac disease (CD). Defects in Tregs are proposed to at least partly explain the imbalance of Th cells found in children with immunologic diseases. Peripheral blood mononuclear cells from 24 children with T1D and/or CD, and reference children (that is, those without any of these diseases) were stimulated with disease-associated antigens (insulin, gluten, transglutaminase [tTG]), and phytohemagglutinin (PHA). The mRNA expression of the Treg-associated marker FOXP3 was analyzed with multiplex real-time RT-PCR. Children with T1D showed both a low spontaneous (P < 0.05) and PHA-induced (P < 0.01) expression of FOXP3 mRNA compared to children with CD. Children with T1D also had a low PHA-induced FOXP3 mRNA expression compared to the group of children diagnosed with both T1D and CD (P < 0.05). Spontaneous (P < 0.05) and PHA-induced (P < 0.05) FOXP3 mRNA expression was high in children with CD compared to reference children. In contrast, stimulation with insulin tended to induce high FOXP3 mRNA expression in T1D children compared to reference children (P = 0.057). In conclusion, children with only T1D generally showed a lower FOXP3 mRNA expression than did children with CD, or with T1D in combination with CD, which suggests impaired regulation of the immune system in children with T1D.
  •  
46.
  • Lahdenperä, Anne, et al. (author)
  • Expression pattern of T-helper 17 cell signaling pathway and mucosal inflammation in celiac disease
  • 2014
  • In: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 49:2, s. 145-156
  • Journal article (peer-reviewed)abstract
    • Objective. The aim was to investigate the mucosal activation of a broad range of genes associated with the T-helper 17 cell (Th17) signaling pathway in children at different stages of celiac disease (CD), including children with increased risk for CD and children with untreated and gluten-free diet (GFD)-treated CD. Material and methods. Small intestinal biopsies were taken from children with untreated and GFD-treated CD, transglutaminase antibody (TGA)-positive children with potential CD, and reference children. Real-time polymerase chain reaction (PCR) arrays were used to study the gene expression pattern of Th17-related genes, and quantitative PCR was used to study the interleukin (IL)-17A expression. Results. The mucosal expression of CD8A was elevated at all stages of CD. Children with untreated CD had diminished levels of IL-17RE, IL-23R, RORc, STAT6, CCL22, NFATC2, IL-18, CD4, CD247, and matrix metalloproteinase (MMP)9 but had elevated levels of MMP3, IL-17, interferon-gamma (IFN-gamma) and CD8A, compared to references. The majority of the aforementioned genes, being differentially expressed in untreated CD, displayed similar expression in GFD-treated children and references. Children with untreated and GFD-treated CD had elevated expression of IFN-gamma but had reduced expression of CD247. Interestingly, children with potential CD displayed reduced FOXP3, IL-21, and IL-17A levels. Conclusion. Mucosal upregulation of Th17 immunity occurs at the late stage of disease and is downregulated with dietary treatment, thus indicating that IL-17 immunity is not a fundamental feature of CD as Th1 immunity, which is not fully downregulated by GFD.
  •  
47.
  • Lahdenperä, Anne, et al. (author)
  • The effect of gluten-free diet on Th1--Th2--Th3-associated intestinal immune responses in celiac disease
  • 2011
  • In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 46:5, s. 538-549
  • Journal article (peer-reviewed)abstract
    • Objective. To study T-helper (Th)1--Th2--Th3 gene activation profile in the small intestine and peripheral blood of children with celiac disease (CD) with special interest in the response to the gluten-free diet (GFD) treatment in order to elucidate an immune dysregulation not triggered by gluten. Material and methods. Small intestinal biopsies and venous blood were taken from seven children with CD (mean age: 8 years, four girls) at presentation and after 1 year of strict GFD. The Th1--Th2--Th3 gene expression profile was examined by real-time PCR arrays. The findings were compared with the corresponding expressions in peripheral blood and small intestinal biopsies from six reference children without CD (mean age: 6 years, four girls). Results. The Th1 gene expression profile including interferon (IFN)-gamma gamma, signal transducer and activator of transcription (STAT) 1 and interferon regulatory factor (IRF) 1 together with reduced interleukin (IL)-2 expression was pronounced in small intestinal biopsies from children with untreated CD. A downregulation of IFN-gamma gamma transcripts was seen after 1 year of GFD, but there was still increased expression of STAT1 and IRF1 in association with low IL-2 expression in spite of eliminated exposure to wheat gluten. By contrast, the decreased intestinal expression of Th2 gene markers observed at presentation was normalized with GFD. The alterations in the mucosal gene expression profile were not reflected in peripheral blood. Conclusion. The GFD did not correct the increased activation of the IFN-gamma gamma signaling pathway related markers and reduced IL-2 expression, suggesting that they represent an immune dysregulation not dependent on gluten exposure.
  •  
48.
  • Lahdenperä, Anna, et al. (author)
  • Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes
  • 2012
  • In: Clinical and Experimental Immunology. - : John Wiley & Sons. - 0009-9104 .- 1365-2249. ; 167:2, s. 226-234
  • Journal article (peer-reviewed)abstract
    • Up-regulation of interleukin (IL)-17 in small intestinal mucosa has been reported in coeliac disease (CD) and in peripheral blood in type 1 diabetes (T1D). We explored mucosal IL-17 immunity in different stages of CD, including transglutaminase antibody (TGA)-positive children with potential CD, children with untreated and gluten-free diet-treated CD and in children with T1D. Immunohistochemistry was used for identification of IL-17 and forkhead box protein 3 (FoxP3)-positive cells and quantitative polymerase chain reaction (qPCR) for IL-17, FoxP3, retinoic acid-related orphan receptor (ROR)c and interferon (IFN)-γ transcripts. IL-1β, IL-6 and IL-17 were studied in supernatants from biopsy cultures. Expression of the apoptotic markers BAX and bcl-2 was evaluated in IL-17-stimulated CaCo-2 cells. The mucosal expression of IL-17 and FoxP3 transcripts were elevated in individuals with untreated CD when compared with the TGA-negative reference children, children with potential CD or gluten-free diet-treated children with CD (P andlt; 0·005 for all IL-17 comparisons and P andlt; 0·01 for all FoxP3 comparisons). The numbers of IL-17-positive cells were higher in lamina propria in children with CD than in children with T1D (P andlt; 0·05). In biopsy specimens from patients with untreated CD, enhanced spontaneous secretion of IL-1β, IL-6 and IL-17 was seen. Activation of anti-apoptotic bcl-2 in IL-17-treated CaCo-2 epithelial cells suggests that IL-17 might be involved in mucosal protection. Up-regulation of IL-17 could, however, serve as a biomarker for the development of villous atrophy and active CD.
  •  
49.
  • Laurin, Pia, et al. (author)
  • Celiac disease in childhood in a Swedish county 1980-2001
  • Other publication (other academic/artistic)abstract
    • Background: The prevalence of celiac disease (CD) in Swedish children has attracted considerable interest during the last decades, and especially the influence of feeding habits on the increased incidence. A national study has reporled a trend of decreasing incidence in the last years after a change in infant feeding recommendations in 1996.Aim: To evaluate, on a geographically defined area, the changes of incidence over time and the influence of the introduction of antibody analysis.Material: All children investigated for suspected CD during 1980-2001 in the county of Östergötland in southeast Sweden. The population of children <18 years is 89,679 (Jan 1, 2001).Results: 1901 children were investigated with small intestinal biopsy, yielding 472 CD cases. The area initially describes the same trends as the national study, hut the annual incidence rate is now increasing again. Median age at diagnosis has increased markedly since 1997 from less than 2 years to above 5 years. Cumulalive incidence is much higher for the birth cohorts 83-96 than 80-82 or 97-00. More biopsies were performed per 1,000 children after the introduction of anti-gliadin antibodies (AGA), and less biopsies after the introduction of antiendomysium antibodies (EMA). Diagnostic accuracy was significantly higher after AGA, and especially after EMA introduction.Conclusions: The incidence rate of CD in small children has shown a large variation over the 22 years observed. Both feeding practice and methods of investigation have changed during the period. Annual incidence rate for the total child population in 2001 approaches the peak value observed in 1994. Median age at first biopsy has rnore than doubled in the last years. There were no conclusive results on whether antibody analyses influenced the diagnostic activity, but they seemed to have increased the diagnostic accuracy.
  •  
50.
  • Laurin, Pia, 1969-, et al. (author)
  • Even small amounts of gluten cause relapse in children with celiac disease
  • 2002
  • In: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Ovid Technologies (Wolters Kluwer Health). - 0277-2116 .- 1536-4801. ; 34:1, s. 26-30
  • Journal article (peer-reviewed)abstract
    • Background: Previously, a gluten challenge was customary to establish the diagnosis of celiac disease in children. There are no clear recommendations on how to perform this challenge or what markers to rely on for timing the biopsy after the challenge. The authors' aim was to monitor gluten intake, clinical symptoms, and antibody kinetics to evaluate the influence of gluten exposure during the challenge.Methods: Twenty-five children under investigation for suspected celiac disease were challenged. One child was excluded because blood samples, food records, or biopsy was lacking. Median age at the postchallenge biopsy was 3.8 (2.7-8.8) years. The families kept daily records of the children's gluten intake and of symptoms that occurred. Blood samples were taken monthly for analysis of antigliadin and endomysium antibodies and total immunoglobulin A (IgA). A third biopsy was performed when clinical symptoms suggested a relapse.Results: All 24 children showed deterioration of the mucosa or elevated antibodies during gluten challenge. Median duration of the challenge was 13 (5-51) weeks, and mean gluten intake was 1.7 (0.2-4.3) g/d and 0.1 (0.02-0.26) g/kg daily.Conclusions: Gluten intake during the challenge varied widely, and the parents were unable to give their children the recommended amount. Despite the small amounts given, all children showed signs of relapse at a clinical, laboratory, or histologic level. Much smaller amounts of gluten than previously suggested seem sufficient to cause relapse during gluten challenge in children.
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