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Genetic characteristics and β-cell Autoimmunity in T1DM Children

Author: Eman M. Saleh
Journal: Journal of the Faculty of Medicine مجلة كلية الطب ISSN: 00419419 Year: 2007 Volume: 49 Issue: 4 Pages: 414-424
Publisher: Baghdad University جامعة بغداد

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Abstract

Background: TIDM is known to be polygenic disease that appears from the interaction of mutation in multiple genes including HLA. The autoimmune mediated destruction of pancreatic β-cells is reflected by the presence of autoantibodies against prominent antigens in the pancreatic β-cells. Objective: This study was designed to investigate the role of HLA-class I and class II antigens in the etiology of type 1 diabetes mellitus (T1DM) and also assessment of glutamic acid decarboxylase (GAD65) autoantibodies in the patients at the onset of the disease. Patients & Methods: Sixty T1DM patients who were newly onset of the disease (diagnosed less than five months) were selected. Eighty apparently healthy control subjects, matched with age, sex and ethnic backgrounds underwent the HLA-typing by lymphocytotoxicity assay. Finally 50 healthy individuals were selected randomly to undergo serological assessment of GAD65 autoantibodies using IRMA method. Results & Conclusion: At HLA-class I region, T1DM patients showed a significant increased frequency of antigen A9 (40.0 vs.18.75%) and B8 (28.33 vs.8.75%) as compared to control subject. At HLA-class II region, DR3 and DR4 were significantly increased in patients (53.33 vs.26.25% and 50.0 vs. 12.5% respectively) as compared to controls. In addition to that, T1DM was significantly associated with DQ2 (33.33 vs.15%) and DQ3 (40.0 vs. 20%) antigens as compared to controls, suggesting that these haplotypes had a role in disease susceptibility, while the frequency of DR2 and DQ1 antigens were significantly lowered in patients compared to controls (6.66 vs. 25% and 6.66 vs. 22.5% respectively). These molecules might had protective effect. Anti-GAD65 autoantibodies were present in 50% of T1DM children especially in older ages and in females more than males. High proportion of GADA was found in the patients carrying HLA-DR3/DR4 heterozygous. In conclusion, susceptibility to T1DM is genetically controlled.


Article
Human Leukocyte Antigens class II influence the expression of Glutamic Acid Decarboxylase auto antibodies in Type Diabetic children and their Siblings

Author: Eman Mahdi Saleh ايمان مهدي صالح
Journal: Al-Kindy College Medical Journal مجلة كلية الطب الكندي ISSN: 18109543 Year: 2010 Volume: 6 Issue: 1 Pages: 52-61
Publisher: Baghdad University جامعة بغداد

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Abstract

Background: The immunogenetic predisposition may be considered as an important factor for the development of Type 1 Diabetes Mellitus (T1DM) in association with the HLA antigens. Objective:This study was designed to investigate the role of HLA-class II antigens in the etiology of type T1DM and in prediction of this disease in siblings, and its effect on expression of glutamic acid decarboxylase autoantibodies (GADA). methods:Sixty children who were newly diagnosed type 1 diabetes (diagnosed less than five months) were selected. Their age ranged from 3-17 years. Another 50 healthy siblings were available for this study, their ages range from 3-16 years. Eighty apparently healthy control subjects, matched with age (4-17) years, sex and ethnic backgrounds (Iraqi Arabs) underwent the HLA-typing examination. Finally 50 healthy individuals were selected randomly to undergo GADA test.Results:At HLA-class II region, DR3 and DR4 were significantly increased in patients (53.33 vs.26.25% and 50.0 vs. 12.5% respectively) as compared to controls. In addition to that, T1DM was significantly associatedwith DQ2 (33.33 vs.15%) and DQ3 (40.0 vs.20%) antigens as compared to controls, suggesting that these antigens had a role in disease susceptibility, while the frequency of DR2 and DQ1 antigens were significantly lowered in patients compared to controls (6.66 vs.25% and 6.66 vs.22.5% respectively). These molecules might have protective effect. In siblings a significant increase frequency of DR4 antigen (34.0 vs.12.5%) was observed in comparison to controls, suggesting that it might be much useful for predicting T1DM in affected families.Anti-GAD autoantibodies were present in 50% of Type 1Diabetic children, and in 16% of their siblings. High proportion of GADA was found in the patients carrying HLA-DR3/DR4 heterozygous.conclusion:Both the T1DM patients and their siblings shared the HLA- DQ1 as protective antigens, while DR3 and DR4 were susceptible one, and high proportion of GADA was found in the T1DM patients and siblings carrying HLA-DR3/DR4 heterozygous.

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