| 1. |
- Andrén Aronsson, Carin, et al.
(författare)
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Age at Gluten Introduction and Risk of Celiac Disease.
- 2015
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 135:2, s. 239-245
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Tidskriftsartikel (refereegranskat)abstract
- The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children.
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| 2. |
- Andrén Aronsson, Carin, et al.
(författare)
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Association of gluten intake during the first 5 years of life with incidence of celiac disease autoimmunity and celiac disease among children at increased risk
- 2019
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Ingår i: JAMA - Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 322:6, s. 514-523
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Tidskriftsartikel (refereegranskat)abstract
- Importance: High gluten intake during childhood may confer risk of celiac disease. Objectives: To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children. Design, Setting, and Participants: The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017. Exposures: Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years. Main Outcomes and Measures: The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels. Results: Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%]). Conclusions and Relevance: Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.
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| 3. |
- Hadley, David, et al.
(författare)
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HLA-DPB1*04:01 Protects Genetically Susceptible Children from Celiac Disease Autoimmunity in the TEDDY Study.
- 2015
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 110:6, s. 915-920
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Tidskriftsartikel (refereegranskat)abstract
- Tissue transglutaminase autoantibodies (tTGAs) represent the first evidence of celiac disease (CD) development. Associations of HLA-DR3-DQA1*05:01-DQB1*02:01 (i.e., DR3-DQ2) and, to a lesser extent, DR4-DQA1*03:01-DQB1*03:02 (i.e., DR4-DQ8) with the risk of CD differ by country, consistent with additional genetic heterogeneity that further refines risk. Therefore, we examined human leukocyte antigen (HLA) factors other than DR3-DQ2 for their contribution to developing tTGAs.
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| 4. |
- Hagopian, William, et al.
(författare)
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Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity
- 2017
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 140:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Few birth cohorts have prospectively followed development of type 1 diabetes (T1D) and celiac disease (CD) autoimmunities to determine timing, extent of co-occurrence, and associated genetic and demographic factors.METHODS: In this prospective birth cohort study, 8676 children at high genetic risk of both diseases were enrolled and 5891 analyzed in median follow-up of 66 months. Along with demographic factors and HLA-DR-DQ, genotypes for HLA-DPB1 and 5 non-HLA loci conferring risk of both T1D and CD were analyzed.RESULTS: Development of persistent islet autoantibodies (IAs) and tissue transglutaminase autoantibodies (tTGAs), as well as each clinical disease, was evaluated quarterly from 3 to 48 months of age and semiannually thereafter. IAs alone appeared in 367, tTGAs alone in 808, and both in 90 children. Co-occurrence significantly exceeded the expected rate. IAs usually, but not always, appeared earlier than tTGAs. IAs preceding tTGAs was associated with increasing risk of tTGAs (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.15-1.91). After adjusting for country, sex, family history, and all other genetic loci, significantly greater co-occurrence was observed in children with a T1D family history (HR: 2.80), HLA-DR3/4 (HR: 1.94) and single-nucleotide polymorphism rs3184504 at SH2B3 (HR: 1.53). However, observed co-occurrence was not fully accounted for by all analyzed factors.CONCLUSIONS: In early childhood, T1D autoimmunity usually precedes CD autoimmunity. Preceding IAs significantly increases the risk of subsequent tTGAs. Co-occurrence is greater than explained by demographic factors and extensive genetic risk loci, indicating that shared environmental or pathophysiological mechanisms may contribute to the increased risk.
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| 5. |
- Hård af Segerstad, Elin M., et al.
(författare)
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Associations of dietary patterns between age 9 and 24 months with risk of celiac disease autoimmunity and celiac disease among children at increased risk
- 2023
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Ingår i: American Journal of Clinical Nutrition. - 0002-9165. ; 118:6, s. 1099-1105
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Tidskriftsartikel (refereegranskat)abstract
- Background: Higher gluten intake in childhood is associated with increased incidence of celiac disease autoimmunity (CDA) and celiac disease. It remains to be studied whether different dietary patterns independent of gluten intake contribute to the incidence. Objectives: This study aimed to explore associations of dietary patterns by age 2 y with risk of CDA and celiac disease in genetically susceptible children. Methods: Data was used from 6726 participants at genetic risk of type 1 diabetes and celiac disease enrolled in the observational cohort, The Environmental Determinants of Diabetes in the Young (TEDDY) study. Children were annually screened for tissue transglutaminase autoantibodies (tTGAs) from age 2 y. Principal component analysis extracted dietary patterns, based on intake of 27 food groups assessed by 3-d food records at age 9 to 24 mo. The primary outcome was CDA (i.e., persistently tTGA-positive in at least 2 consecutive samples), and the secondary outcome was celiac disease. During follow-up to mean age 11.0 (standard deviation 3.6) y, 1296 (19.3%) children developed CDA, and 529 (7.9%) were diagnosed with celiac disease. Associations of adherence to dietary patterns (per 5-unit increase) with the study outcomes were estimated by Cox regression models adjusted for risk factors including gluten intake. Results: At age 9 mo, a dietary pattern higher in the food groups vegetable fats and milk was associated with reduced risk of CDA (hazard ratio [HR]: 0.88; 95% confidence interval [CI]: 0.79, 0.98; P = 0.02). At 24 mo, a dietary pattern higher in the food groups wheat, vegetable fats, and juices, and lower in milk, meat, and oats at age 24 mo was associated with increased risk of CDA (HR: 1.18; 95% CI: 1.05, 1.33; P < 0.001) and celiac disease (HR: 1.24; 95% CI: 1.03, 1.50; P = 0.03). Conclusions: Dietary patterns in early childhood are associated with risk of CDA and celiac disease in genetically predisposed children, independent of gluten intake.
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| 6. |
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| 7. |
- Kemppainen, Kaisa M, et al.
(författare)
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Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity
- 2017
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Ingår i: JAMA Pediatrics. - : American Medical Association (AMA). - 2168-6211 .- 2168-6203. ; 171:12, s. 1217-1225
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Evidence is lacking regarding the consequences of antibiotic use in early life and the risk of certain autoimmune diseases.Objective: To test the association between early-life antibiotic use and islet or celiac disease (CD) autoimmunity in genetically at-risk children prospectively followed up for type 1 diabetes (T1D) or CD.Design, Setting, and Participants: HLA-genotyped newborns from Finland, Germany, Sweden, and the United States were enrolled in the prospective birth cohort of The Environmental Determinants of Diabetes in the Young (TEDDY) study between November 20, 2004, and July 8, 2010. The dates of analysis were November 20, 2004, to August 31, 2014. Individuals from the general population and those having a first-degree relative with T1D were enrolled if they had 1 of 9 HLA genotypes associated with a risk for T1D.Exposures: Parental reports of the most common antibiotics (cephalosporins, penicillins, and macrolides) used between age 3 months and age 4 years were recorded prospectively.Main Outcomes and Measures: Islet autoimmunity and CD autoimmunity were defined as being positive for islet or tissue transglutaminase autoantibodies at 2 consecutive clinic visits at least 3 months apart. Hazard ratios and 95% CIs calculated from Cox proportional hazards regression models were used to assess the relationship between antibiotic use in early life before seroconversion and the development of autoimmunity.Results: Participants were 8495 children (49.0% female) and 6558 children (48.7% female) enrolled in the TEDDY study who were tested for islet and tissue transglutaminase autoantibodies, respectively. Exposure to and frequency of use of any antibiotic assessed in this study in early life or before seroconversion did not influence the risk of developing islet autoimmunity or CD autoimmunity. Cumulative use of any antibiotic during the first 4 years of life was not associated with the appearance of any autoantibody (hazard ratio [HR], 0.98; 95% CI, 0.95-1.01), multiple islet autoantibodies (HR, 0.99; 95% CI, 0.95-1.03), or the transglutaminase autoantibody (HR, 1.00; 95% CI, 0.98-1.02).Conclusions and Relevance: The use of the most prescribed antibiotics during the first 4 years of life, regardless of geographic region, was not associated with the development of autoimmunity for T1D or CD. These results suggest that a risk of islet or tissue transglutaminase autoimmunity need not influence the recommendations for clinical use of antibiotics in young children at risk for T1D or CD.
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| 8. |
- Kemppainen, Kaisa M, et al.
(författare)
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Factors That Increase Risk of Celiac Disease Autoimmunity After a Gastrointestinal Infection in Early Life
- 2017
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 15:5, s. 5-702
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Little is known about the pathogenic mechanisms of gluten immunogenicity in patients with celiac disease. We studied temporal associations between infections and the development of celiac disease autoimmunity, and examined effects of HLA alleles, rotavirus vaccination status, and infant feeding. Methods: We monitored 6327 children in the United States and Europe carrying HLA risk genotypes for celiac disease from 1 to 4 years of age for presence of tissue transglutaminase autoantibodies (the definition of celiac disease autoimmunity), until March 31, 2015. Parental reports of gastrointestinal and respiratory infections were collected every third month from birth. We analyzed time-varying relationships among reported infections, rotavirus vaccination status, time to first introduction of gluten, breastfeeding, and risk of celiac disease autoimmunity using proportional hazard models. Results: We identified 13,881 gastrointestinal infectious episodes (GIE) and 79,816 respiratory infectious episodes. During the follow-up period, 732 of 6327 (11.6%) children developed celiac disease autoimmunity. A GIE increased the risk of celiac disease autoimmunity within the following 3 months by 33% (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.11-1.59). This risk increased 2-fold among children born in winter and introduced to gluten before age 6 months (HR, 2.08; 95% CI, 1.46-2.98), and increased 10-fold among children without HLA-DQ2 alleles and breastfed for fewer than 4 months (HR, 9.76; 95% CI, 3.87-24.8). Risk of celiac disease autoimmunity was reduced in children vaccinated against rotavirus and introduced to gluten before age 6 months (HR, 0.57; 95% CI, 0.36-0.88). Conclusions: Gastrointestinal infections increase the risk of celiac disease autoimmunity in children with genetic susceptibility to this autoimmune disorder. The risk is modified by HLA genotype, infant gluten consumption, breastfeeding, and rotavirus vaccination, indicating complex interactions among infections, genetic factors, and diet in the etiology of celiac disease in early childhood.
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| 9. |
- Koletzko, Sibylle, et al.
(författare)
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Caesarean Section on The Risk of Celiac Disease in the Offspring : The Teddy Study
- 2018
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition. - 0277-2116. ; 66:3, s. 417-424
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: Caesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort. METHODS:: From 2004 to 2010 infants from the general population who tested positive for HLA DR3-DQ2 or DR4-DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study. Children were annually screened for transglutaminase autoantibodies, if positive re-tested after 3–6 months and those persistently positive defined as CDA. Associations of C-section with maternal (age, education level, parity, pre-pregnancy weight, diabetes, smoking, weight gain during pregnancy) and child characteristics (gestational age, birth weight) were examined by Fisherʼs exact test or Wilcoxon rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models. RESULTS:: Of 6,087 analyzed singletons 1600 (26%) were born by C-section (Germany 38%, US 37%, Finland 18%, Sweden 16%), the remaining vaginally without instrumental support; 979 (16%) had developed CDA and 343 (6%) CD. C-section was associated with lower risk for CDA (HR?=?0.85, [95% CI 0.73, 0.99], p?=?0.032) and CD (HR?=?0.75, [95% CI 0.58, 0.98], p?=?0.034). After adjusting for country, sex, HLA-genotype, CD in family, maternal education and breastfeeding duration, significance was lost for CDA (HR?=?0.91, [95% CI 0.78, 1.06], p?=?0.20) and CD (HR?=?0.85, [95% CI 0.65, 1.11], p?=?0.24). Pre-surgical ruptured membranes had no influence on CDA or CD development. CONCLUSION:: C-section is not associated with increased risk for CDA or CD in the offspring.
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| 10. |
- Li, Marcella, et al.
(författare)
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A Report on the International Transglutaminase Autoantibody Workshop for Celiac Disease
- 2009
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 104:1, s. 154-163
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Measurement of transglutaminase autoantibodies (TGAA) is considered to be the most efficient single serologic test for celiac disease (CD) by the American Gastroenterological Association Institute. We hypothesized that a large international collaborative effort toward improving and standardizing TGAA measurement is both feasible and necessary. The primary aim of this workshop is to compare TGAA assays among various research and clinical laboratories and examine assay concordance and improve (and eventually standardize) the TGAA assay. METHODS: A total of 20 laboratories (5 commercial laboratories, 15 research and clinical laboratories) participated that included enzyme-linked immunosorbent assay (ELISA) and radiobinding assays. A total of 150 serum samples were distributed to each laboratory, with each laboratory receiving an equal aliquot that was coded and blinded, composed of 100 healthy control sera and 50 CD sera. RESULTS: Laboratory sensitivity ranged from 69% to 93% and specificity ranged from 96% to 100%. By receiver operator characteristic analysis, the area under the curve (C index) ranged from 0.9488 to 0.9904. When analyzing for linear correlation, r-squared was as high as 0.8882 but as low as 0.4244 for the celiac samples between different laboratories performing ELISA. CONCLUSIONS: This transglutaminase autoantibody workshop allows for larger-scale international participation for the purposes of improving and eventually standardizing the TGAA assay with subsequent workshops.
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