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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.


Article
T-Cells Proliferation and Serum Cytokine levels in Type 1 Diabetic Children

Author: Eman Mahdi Saleh ايمان مهدي صالح
Journal: Al-Kindy College Medical Journal مجلة كلية الطب الكندي ISSN: 18109543 Year: 2011 Volume: 7 Issue: 2 Pages: 16-26
Publisher: Baghdad University جامعة بغداد

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Abstract

Background: There is plenty of evidence suggesting that involvement of several groups of viruses in the development and / or acceleration of Type 1 Diabetes Mellitus (T1DM). Objective: To analyze the T- cell proliferation in the presence of Coxsackie virus B5 (CVB5), Polio and Adenovirus antigens in addition to assessment of Interferon- gamma (IFN-γ), Interleukins (IL-10 and IL-6). Methods: In 60 Iraqi T1DM children with recent onset of T1DM, Lymphocyte proliferation was analyzed using Methylthiazol tetrazolium (MTT) assay by culturing Peripheral Blood Lymphocytes (PBLs) with Coxsackie Virus B5 (CVB5), Adenovirus, and Polio vaccine. Serum Interferon-γ, IL-10 and IL-6 were quantified by sandwich ELISA. Results: No significant differences were shown in the PBL proliferative percentage in response to Con-A mitogen and tested viruses (CVB5 and Adenovirus) between T1DM and healthy controls, but it showed a significant decline in patients in response to Polio vaccine. Higher significant serum levels of IFN-γ, IL-10, and Il-6 were observed in the investigated patients compared to controls (p<0.05). Mean PBL proliferative percentage in response to tested viral antigens was correlated with the serum IFN-γ, IL-6 and IL-10 levels. Conclusions: In children with new- onset diabetes, mean proliferative percentage of Peripheral Blood Lymphocytes was generally decreased. A significant elevation of serum levels of IFN-γ, IL-10 and IL-6 were observed, which is significantly correlated to mean proliferative responses of PBL to viral antigens.

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