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| 2. |
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| 3. |
- Duan, Rui-Dong, et al.
(författare)
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Human meconium contains significant amounts of alkaline sphingomyelinase, neutral ceramidase, and sphingolipid metabolites.
- 2007
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 61:1, s. 61-66
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal alkaline sphingomyelinase (Alk-SMase) and neutral ceramidase may catalyze the hydrolysis of endogenous sphin-gomyelin (SM) and milk SM in human-milk fed infants. The enzymes generate sphingolipid metabolites that may influence gut maturation. Alk-SMase also inactivates platelet-activating factor (PAF) that is involved in the pathogenesis of necrotizing enterocolitis (NEC). We examined whether the two enzymes are expressed in both preterm and term infants and analyzed Alk-SMase, neutral ceramidase, SM, and sphingolipid metabolites in meconium. Meconium was collected from 46 preterm (gestational ages 23-36 wk) and 38 term infants (gestational ages 37-42 wk) and analyzed for Alk-SMase using C-14-choline-labeled SM and for neutral ceramidase using C-14-octanoyl-sphingosine as substrates. Molecular species of SM, ceramide, and sphingosine were analyzed by high-performance liquid chromatography mass spectroscopy. Meconium contained significant levels of Alk-SMase and ceramidase at all gestational ages. It also contained 16-24 carbon molecular species of SM, palmitoyl-and stearoyl-sphingosine, and sphingosine. There were positive correlations between levels of SM and ceramide and between ceramide and sphingosine levels. In conclusion, Alk-SMase and ceramidase are expressed in the gut of both preterm and term newborn infants and may generate bioactive sphingolipid messengers.
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| 6. |
- Jönsson, Lena M, et al.
(författare)
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A dosimetry model for the small intestine incorporating intestinal wall activity and cross-doses.
- 2002
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Ingår i: Journal of Nuclear Medicine. - 0161-5505. ; 43:12, s. 1657-1664
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Tidskriftsartikel (refereegranskat)abstract
- Current internal radiation dosimetry models for the small intestine, and for most walled organs, lack the ability to account for the activity uptake in the intestinal wall. In existing models the cross-dose from nearby loops of the small intestine is not taken into consideration. The aim of this investigation was to develop a general model for calculating the absorbed dose to the radiation-sensitive cells in the small intestinal mucosa from radionuclides located in the small intestinal wall or contents. Methods: A model was developed for calculation of the self-dose and cross-dose from activity in the intestinal wall or contents. The small intestine was modeled as a cylinder with 2 different wall thicknesses and with an infinite length. Calculations were performed for various mucus thicknesses. S values were calculated using the EGS4 Monte Carlo simulation package with the PRESTA algorithm and the simulation results were integrated over the depth of the radiosensitive cells. The cross-organ dose was calculated by summing the dose contributions from other intestinal segments. Calculations of S values for self-dose and cross-dose were made for monoenergetic electrons, 0.050–10 MeV, and for the radionuclides 99mTc, 111In, 131I, 67Ga, 90Y, and 211At. Results: The self-dose S value from activity located in the small intestinal wall is considerably greater than the S values for self-dose from the contents and the cross-dose from wall and contents except for high electron energies. For all radionuclides investigated and for electrons 0.10–0.20 MeV and 8–10 MeV in energy, the cross-dose from activity in the contents is higher than the self-dose from the contents. The mucus thickness affects the S value when the activity is located in the contents. Conclusion: A dosimetric model for the small intestine was developed that takes into consideration the localization of the radiopharmaceutical in the intestinal wall or in the contents. It also calculates the contribution from self-dose and cross-dose. With this model, more accurate calculations of absorbed dose to radiation-sensitive cells in the intestine are possible.
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| 7. |
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| 8. |
- Jönsson, Lena S, et al.
(författare)
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Influence of glutathione-related genes on symptoms and immunologic markers among vulcanization workers in the southern Sweden rubber industries.
- 2008
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 81:7, s. 913-919
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim was to elucidate the role of genetic variants on symptoms of the eyes and airways, headache and nausea, as well as on immunologic markers, among vulcanization workers in the contemporary Swedish rubber industry. Polymorphisms in genes, which are involved in the defense against reactive oxygen species and metabolism of toxic substances present in the vulcanization fumes, were analyzed. METHODS: One hundred and forty-five exposed and 117 unexposed workers were included in the study. Medical and occupational histories were obtained in structured interviews. Symptoms were recorded and immunologic markers analyzed in blood. Polymorphisms in glutathione-related genes (glutamate cysteine ligase catalytic subunit (GCLC)-129, glutamate cysteine ligase modifier subunit (GCLM)-588, glutathione S-transferase alpha 1 (GSTA1)-52, GSTM1*O, GSTP1-105, GSTP1-114, and GSTT1*O) were analyzed by Taqman-based allelic discrimination and ordinary PCR. RESULTS: A protective effect of GSTA1-52 (G/A + A/A) genotype on symptoms and immunologic cells, in particular among exposed workers, was suggested. Exposed workers with GSTT1*O had increased risk of nosebleed compared to exposed workers with GSTT1*1. Exposed workers with GSTP1-105 (ile/val + val/val) had decreased levels of total immunoglobulin E (IgE) compared to exposed workers with GSTP1-105 ile/ile. GCLC-129 variant genotype demonstrated increased levels of immunologic cells among exposed workers, although statistical significance was not reached. CONCLUSION: Our data indicate that hereditary factors influence the susceptibility to symptoms and the immunologic response of workers in the rubber industry.
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| 9. |
- Jönsson, Lena S, et al.
(författare)
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Levels of 1-hydroxypyrene, symptoms and immunologic markers in vulcanization workers in the southern Sweden rubber industries.
- 2008
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 82, s. 131-137
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to determine urinary 1-hydroxypyrene (1-HP) levels in contemporary Swedish vulcanization workers and in controls. These levels were used as an index substance for vulcanization fumes, as well as a biomarker for polycyclic aromatic hydrocarbons (PAHs). The risk of symptoms and changed levels of immunologic markers were investigated in relation to the 1-HP levels. METHODS: Included in the study were 163 exposed workers and 106 controls. Medical and occupational histories were obtained by structured interviews. Symptoms were recorded and immunologic markers analysed in blood by routine analysis methods. Levels of 1-HP were determined by liquid chromatography and fluorescence detection. RESULTS: The highest levels of 1-HP were found among exposed workers using injection and compression vulcanization and lower levels were found among exposed workers vulcanizing with salt bath, hot air, microwaves or fluid-bed. Compared to controls, exposed workers had increased risks of eye symptoms, nosebleeds, burning and dry throat, hoarseness, severe dry cough, nausea and headache. Furthermore, exposed workers had elevated levels of neutrophils and total IgG (immunoglobulin subclass G). However, only for severe dry cough an evident exposure-response relationship with urinary 1-HP levels was found. CONCLUSIONS: This work clearly shows increased levels of urinary 1-HP in Swedish vulcanization workers. Furthermore, it demonstrates an increased risk of several symptoms and elevated levels of some immunologic markers in these workers. However, no obvious exposure-response relationships were found.
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| 10. |
- Jönsson, Lena S, et al.
(författare)
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Levels of 2-thiothiazolidine-4-carboxylic acid (TTCA) and effect modification of polymorphisms of glutathione-related genes in vulcanization workers in the southern Sweden rubber industries.
- 2007
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 80:7, s. 589-598
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Workers in the rubber industry are exposed to a complex mixture of hazardous substances and have increased risk of developing several diseases. However, there is no up to date survey examining the exposure in the Swedish rubber industry. One of the toxic compounds in the industry is carbon disulfide (CS2), which is biotransformed to 2-thiothiazolidine- 4carboxylic acid (TTCA). TTCA is used as a biomarker of CS2 exposure, but there seem to exist inter- and intraindividual variability; which could partly be due to genetic variation. The aim of the study was to determine TTCA levels and the modifying effects of glutathione-related genes in a group of Swedish rubber workers. Methods Urine was collected from both exposed workers and controls during the last 4 h of the work shift. The level of TTCA in urine was analyzed by liquid chromatograpy tandem mass spectrometry. Genotyping of the single nucleotide polymorphisms GCLC-129, GCLM-588, GSTA1-52, GSTP1-105 and GSTP1-114 and deletions of GSTM1 and GSTT1 were performed with real-time PCR or ordinary PCR and subsequent agarose electrophoresis. Results The highest levels of TTCA were found among workers curing with salt bath, hot air, microwaves or Xuid-bed, and lower levels were found among workers curing with injection and compression molding. Furthermore, with respect to GSTM1 and GSTT1 there were statistically significant differences in TTCA-levels between genotypes among exposed workers but not among controls. The other five polymorphisms had no impact on the TTCA levels. Conclusions The present study demonstrates relatively high levels of TTCA in urine from Swedish rubber workers. Polymorphisms in GSTM1 and GSTT1 modify the levels.
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| 11. |
- Jönsson, Lena S, et al.
(författare)
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Lung function in relation to 2-thiothiazolidine-4-carboxylic Acid and genetic effect modification among rubber workers in sweden.
- 2008
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Ingår i: Journal of Occupational and Environmental Medicine. - 1536-5948. ; 50:9, s. 1006-1012
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: What is the risk of impaired lung function in contemporary Swedish rubber workers and are there modifying effects of genetic variants? METHODS:: Included in the study were 159 rubber exposed and 118 not-rubber exposed workers. Lung function was analyzed as forced vital capacity percent of predicted and forced expiratory volume in 1 second percent of predicted. Levels of 2-thiothiazolidine-4-carboxylic acid (a marker of carbon disulfide and vulcanization fumes) was assessed with liquid chromatography tandem mass spectrometry. Polymorphisms in glutathione-related genes were analyzed by Taqman-based allelic discrimination and ordinary polymerase chain reaction. RESULTS:: There was an association between increasing levels of 2-thiothiazolidine-4-carboxylic acid and impaired lung function among exposed workers. The association was modified by glutathione S-transferase alpha 1 (GSTA1)-52 and GSTP1-114. GSTM1 had an influence on lung function among unexposed workers. CONCLUSIONS:: There may be a risk of impaired lung function in contemporary rubber workers. Gene-modifying effects may be considered in risk assessments.
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| 12. |
- Jönsson, Lena S, et al.
(författare)
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N-nitrosamines in the southern Swedish rubber industries - exposure, health effects, and immunologic markers
- 2009
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 35:3, s. 11-203
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was twofold: (i) to evaluate the air levels of N-nitrosamines in the Swedish rubber industry and (ii) to estimate the risk of symptoms and changed levels of immunologic markers in relation to these levels.METHODS: Using adsorption tubes, we collected samples of N-nitrosamines in the breathing zone of 96 rubber workers and analyzed them with liquid chromatography tandem mass spectrometry. Of these 96 workers, 66 were included in a medical examination and blood analysis together with an additional 106 rubber workers and 118 unexposed subjects. Medical and occupational histories were obtained in structured interviews, symptoms were recorded and immunologic markers analyzed in blood.RESULTS: The sum of N-nitrosamines ranged from less than the limit of detection to 36 microg/m (3)and differed with the vulcanization (ie, curing process) method used. Workers vulcanizing with a salt bath had the highest levels (median 4.2 microg/m (3)). Compared to the unexposed subjects, the rubber workers had an increased risk of nosebleeds, eye and throat symptoms, hoarseness, cough, nausea, headache, and changed levels of eosinophils and total immunoglobulin G (IgG). However, we found no clear exposure-response relationship with the symptoms or the immunologic markers studied.CONCLUSIONS: High levels of N-nitrosamines were found and must be lowered considerably in order to decrease the risk of cancer. There is a need for an occupational exposure limit for N-nitrosamines in Sweden. The lack of exposure-response relationships with the subacute symptoms examined in this study may be due to a healthy-worker selection or to the possibility that the symptoms are caused by an exposure not co-varying with N-nitrosamines.
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| 13. |
- Jönsson, Lena S, et al.
(författare)
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Symptoms and immunologic markers among vulcanization workers in rubber industries in southern Sweden
- 2007
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Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 33:4, s. 272-279
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to estimate the risk of symptoms and the possible derangement of levels of immunologic markers for contemporary Swedish rubber workers. Furthermore, the relation between exposure and these biomarkers of response was examined using urinary levels of 2-thiothiazolidine-4-carboxylic acid (TTCA), which reflect the exposure. Methods Included in the study were 166 exposed workers and 117 controls. Medical and occupational histories were obtained in structured interviews. Symptoms were recorded, and immunologic markers were analyzed in blood. Urinary levels of TTCA were determined by liquid chromatography tandem mass spectrometry. Results Compared with the controls, the exposed workers had increased risks of eye symptoms [odds ratio (OR) 3.0], nose bleeds (OR 4.0), burning and dry throat (OR 3.0), hoarseness (OR 2.4), severe dry cough (OR 3.8), nausea (OR 4.3), and headache (OR 2.5). When the exposed workers were divided into three groups according to the TTCA levels, the highest risks were observed among the exposed workers with intermediate TTCA levels. Furthermore, the exposed workers in all of the TTCA subgroups had elevated concentrations of total immunoglobulin G when compared with the controls. Elevated concentrations of leukocytes, neutrophils, and eosinophils were observed in the group with high TTCA levels. Conclusions This work shows an increased risk of several symptoms and elevated levels of some immunologic markers among exposed workers in Swedish rubber industries. In addition, relationships between urinary levels of TTCA and some biomarkers of response were reported.
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| 14. |
- Kanatsuna, N, et al.
(författare)
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Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes
- 2015
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Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 82:4, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (P < 0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.
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| 15. |
- Knutsen Rydberg, Ellen, 1969, et al.
(författare)
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Hypoxia increases LDL oxidation and expression of 15-lipoxygenase-2 in human macrophages
- 2004
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Ingår i: Arterioscler Thromb Vasc Biol. ; 24:11, s. 2040-2045
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Macrophage-mediated oxidation of low-density lipoprotein (LDL) by enzymes, such as the lipoxygenases, is considered of major importance for the formation of oxidized LDL during atherogenesis. Macrophages have been identified in hypoxic areas in atherosclerotic plaques. METHODS AND RESULTS: To investigate the role of hypoxia in macrophage-mediated LDL oxidation, we incubated human monocyte-derived macrophages with LDL under normoxic (21% O2) or hypoxic (0% O2) conditions. The results showed that hypoxic macrophages oxidized LDL to a significantly higher extent than normoxic cells. Interestingly, the mRNA and protein expression of 15-lipoxygenase-2 (15-LOX-2) as well as the activity of this enzyme are elevated in macrophages incubated at hypoxia. Both the unspliced 15-LOX-2 and the spliced variant 15-LOX-2sv-a are found in macrophages. In addition, 15-LOX-2 was identified in carotid plaques in some macrophage-rich areas but was only expressed at low levels in nondiseased arteries. CONCLUSIONS: In summary, these observations show for the first time that 15-LOX-2 is expressed in hypoxic macrophages and in atherosclerotic plaques and suggest that 15-LOX-2 may be one of the factors involved in macrophage-mediated LDL oxidation at hypoxia.
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| 16. |
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| 17. |
- Ohlsson, Lena, et al.
(författare)
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Sphingolipids in human ileostomy content after meals containing milk sphingomyelin.
- 2010
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Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 91, s. 672-678
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sphingomyelin occurs in modest amounts in the diet, in sloughed mucosal cells, and in bile. It is digested by the mucosal enzymes alkaline sphingomyelinase and ceramidase. In humans, alkaline sphingomyelinase is also secreted in bile. The digestion of sphingomyelin is slow and incomplete, which has been linked to the inhibition of cholesterol absorption and colonic carcinogenesis. OBJECTIVE: We evaluated whether the supply of moderate amounts of milk sphingomyelin increases the exposure of the colon to sphingomyelin and its metabolites. DESIGN: Two experimental series were performed. In experiment A, we measured the content of sphingomyelin and ceramide in human ileostomy content by HPLC during 8 h after consumption of a test meal containing 250 mg milk sphingomyelin. In experiment B, we measured the molecular species of sphingomyelin and ceramide by HPLC-tandem mass spectrometry after doses of 50, 100, or 200 mg sphingomyelin. RESULTS: In experiment A, the average increase in ileostomy content of ceramide plus sphingomyelin amounted to 19% of the fed dose of sphingomyelin. In experiment B, the output of C-22:0-sphingomyelin, C-23:0-sphingomyelin, C-24:0-sphingomyelin, and sphingosine increased significantly and palmitoyl-sphingomyelin increased proportionally less. Outputs and concentrations of palmitoyl-ceramide and sphingosine showed great individual variation, and stearoyl-sphingomyelin and stearoyl-ceramide did not increase after the meals. Although the output of long-chain sphingomyelin species increased significantly, the data indicated that >81% of all measured sphingomyelin species had been digested. CONCLUSIONS: Humans digest and absorb most of the sphingomyelin in normal diets. The level of sphingolipid metabolites to which the colon is exposed can, however, be influenced by realistic amounts of dietary sphingomyelin.
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| 19. |
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| 21. |
- Almqvist, Monica, et al.
(författare)
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European Medical Imaging Technology Training, EMIT – ett prisbelönt EU-utbildningsprojekt
- 2005
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Ingår i: [Host publication title missing].
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Konferensbidrag (refereegranskat)abstract
- I ett sameuropeiskt Leonardo da Vinci-projekt har utvecklats ett internationellt utbildnings- och praktikpa- ket för blivande sjukhusfysiker [1-3]. Utbildningspaketet innehåller praktiska och kliniska övningsuppgifter där delta- garna tränas i för en sjukhusfysiker vanligt förekommande arbetsuppgifter. Målet har varit att det skall ge sjukhusfysi- kern den praktiska kompetens som krävs av det europeiska regelverket inom ämnesområdena magnetresonans (MRI), ultraljud, röntgendiagnostik, nuklearmedicin och strålbe- handling. Utbildningsmaterialet är webbaserat med en stor bilddata- bas och används redan i nära 70 länder runt om i världen. EMIT-projektet (European Medical Imaging Technology Training) belönades i december 2004 med det första Leonar- do da Vinci priset som delades ut till de tre bästa av totalt 4000 EU-projekt inom praktisk yrkesrelaterad utbildning. I projektet har vi konfronterats med den pedagogiska ut- maningen att förmedla praktisk kunskap, i sjukhusmiljöer med mycket olika förutsättningar beroende på vilket land deltagarna arbetar i. En omöjlig uppgift kan tyckas, men eftersom materialet är sammanställt av några av Europas starkaste forsknings- och utbildningsgrupper inom respekti- ve område så har det visat sig vara en stor tillgång och varje användare utnyttjar materialet efter sina egna behov. En an- nan erfarenhet är samarbetet över nationsgränser där vi har utnyttjat och konfronterats med likheter och oliktänkande inte minst vad gäller pedagogik och didaktik. Vi har dessut- om fått ett stort kontaktnät och många goda vänner. Den här presentationen beskriver delar av utbildningspaketet och erfarenheter av samarbetsprojektet.
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| 22. |
- Ambjörn, Lena, et al.
(författare)
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Gifter, droger och mat : om läkemedel i den medeltida medicinen i islam
- 2008
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Ingår i: Förbistringar och förklaringar : festskrift till Anders Piltz. - 9789187976292 ; , s. 25-33
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Bokkapitel (populärvet., debatt m.m.)abstract
- Drugs prepared from organic and mineral substances have, throughout history, held a central position when it comes to preventing and curing disease. In Galenic medicine, foodstuffs, drugs and deadly substances, or poisons, were all accredited with the potential to affect the constitution of the body. While the Galenic paradigm continued to dominate formal medicine in the Middle Ages, the language used for scientific communication changed from Greek and Syriac to Arabic. This means that our knowledge of most aspects of medieval highly qualified medicine depends on the study of Arabic sources. The preserved Arabic material on pharmacology is extensive, and it is clear that physicians in the Arabo-Islamic cultural sphere have contributed to the knowledge of both single substances and compound preparations.
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| 23. |
- Anderberg, Peter, et al.
(författare)
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Enabling design
- 2009
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Ingår i: Ergonomics for Rehabilitation Professionals. - Boca Raton : CRC Press. - 9780849381461 ; , s. 477-506
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Bokkapitel (refereegranskat)abstract
- Designed to meet the diverse needs of therapists, this book presents a new approach to rehabilitation that integrates ergonomics concepts to address the wide range of problems commonly encountered by professionals. The first section addresses general concepts such as anthropometry and tissue mechanics. The next section explores whole body biomechanics, demonstrating the ergonomic effects of physiological and biomechanical factors. The third section focuses on regional biomechanics, explaining the rationale for ergonomic intervention. The final section of the text offers with a detailed discussion of the ergonomic paradigm in rehabilitation, including the use of physical demands analysis.
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| 24. |
- Andersson, Cecilia K, et al.
(författare)
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The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes.
- 2011
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 44, s. 394-405
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell cytoplasm (ICA) in combination with human leukocyte antigen (HLA) would improve the diagnostic sensitivity of childhood type 1 diabetes by detecting the children who otherwise would have been autoantibody-negative. Methods: A total of 686 patients diagnosed in 1996-2005 in Skåne were analyzed for all the seven autoantibodies [arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA] in addition to HLA-DQ genotypes. Results: Zinc transporter 8 autoantibody to either one or all three amino acid variants at position 325 (ZnT8RWQA) was found in 65% (449/686) of the patients. The frequency was independent of age at diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients from 7.5 to 5.4%-a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 years of age had no autoantibody at diagnosis. Diagnosis without any islet autoantibody increased with increasing age at onset. DQA1-B1(*)X-0604 was associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with IAA. Conclusions: This study revealed that (1) the ZnT8RWQA was common, independent of age; (2) multiple autoantibodies were common among the young; (3) DQA1-B1(*)X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between autoantibody pairs was common for all combinations except IAA. These results suggest that ZnT8RWQA is a necessary complement to the classification and prediction of childhood type 1 diabetes as well as to randomize the subjects in the prevention and intervention of clinical trials.
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| 25. |
- Andersson, C, et al.
(författare)
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The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes
- 2011
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Ingår i: Autoimmunity. - : Taylor & Francis. - 0891-6934 .- 1607-842X. ; 44:5, s. 394-405
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell cytoplasm (ICA) in combination with human leukocyte antigen (HLA) would improve the diagnostic sensitivity of childhood type 1 diabetes by detecting the children who otherwise would have been autoantibody-negative.Methods: A total of 686 patients diagnosed in 1996–2005 in Skåne were analyzed for all the seven autoantibodies [arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA] in addition to HLA-DQ genotypes.Results: Zinc transporter 8 autoantibody to either one or all three amino acid variants at position 325 (ZnT8RWQA) was found in 65% (449/686) of the patients. The frequency was independent of age at diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients from 7.5 to 5.4%—a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 years of age had no autoantibody at diagnosis. Diagnosis without any islet autoantibody increased with increasing age at onset. DQA1-B1*X-0604 was associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with IAA.Conclusions: This study revealed that (1) the ZnT8RWQA was common, independent of age; (2) multiple autoantibodies were common among the young; (3) DQA1-B1*X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between autoantibody pairs was common for all combinations except IAA. These results suggest that ZnT8RWQA is a necessary complement to the classification and prediction of childhood type 1 diabetes as well as to randomize the subjects in the prevention and intervention of clinical trials.
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