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ASSOCIATION BETWEEN HLA-CLASS II ALLELES AND T-CELL PROLIFERATION IN RESPONSE TO ENTEROVIRUSES AND ADENOVIRUS ANTIGENS IN NEWLY DIAGNOSED CHILDREN WITH TYPE 1 DIABETES MELLITUS
العلاقة بين مستضدات التطابق النسيجي- الصنف الثاني والفعالية الوظيفية للخلايا اللمفية بعد تحفيزها بمستضدات الحمات المعوية والحمات الغدية في الاطفال المصابين حديثاً بالسكري من النوع الأول

Author: ايمان مهدي صالح
Journal: Iraqi Journal of Biotechnology المجلة العراقية للتقانات الحياتية ISSN: 18154794 Year: 2010 Volume: 9 Issue: 2 Pages: 180-190
Publisher: Baghdad University جامعة بغداد

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Abstract

Viruses may be involved in the pathogenesis of Type 1 Diabetes Mellitus (T1DM), either through direct β-cell infection or as triggers of autoimmunity. T- cell proliferation was evaluated in response to Enteroviruses antigens including Coxsackievirus B and Poliovirus in addition to Adenovirus in an HLA- matched population of children with T1DM and in children who were apparently healthy. A total of 60 Iraqi T1DM children were included in the presents study. They were with new onset of the disease. For the purpose of comparisons, 50 apparently healthy control subjects were also selected. HLA typing was measured by microlymphocytotoxicity, while methylthiazoltetrazolium (MTT) assay was used for lymphocyte proliferation by culturing peripheral blood lymphocytes (PBL) with Coxsackievirus B5, Adenovirus 3, 4 and 7 and Poliovaccine. 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 PBL proliferative percentage of patients showed a significant decline in response to Poliovaccine. HLA class II (-DR3, DR4, DQ2 and DQ3) antigens were significantly increased in T1DM patients and they played an important role in the etiology of the disease. Strong T-cell proliferation in response to the tested viral antigens were observed to be related to HLA-DR4 and HLA-DQ3 antigens, whereas the HLA-DR3 and HLA-DQ2 alleles were associated with week responsiveness to the same antigens. However, in children with new- onset diabetes, responses were decreased and this could be caused by trapping of virus- specific T- cells in the pancreas.

أثبتت العديد من الدراسات أن للفايروسات دوراً تؤديه في احداث امراضية مرض السكر من النوع الاول بالاصابة المباشرة لخلايا بيتا في البنكرياس أو بتحفيزالمناعه الذاتية. أجريت الدراسة لغرض تقييم الفعالية الوظيفية للخلايا اللمفية بعد تحفيزها بمستضدات الحمات المعوية والتي تشمل فايروس الكوكساكي نوع- ب وفايروس شلل الاطفال فضلا عن الحمة الغدية في مجموعة من الاطفال المصابين بمرض السكري من النوع الاول ومجموعة من الاطفال الاصحاء المطابقين لمستضدات التطابق النسيجي من الصنف الثاني. شملت الدراسة ستون مريضاً حديثي الاصابة بمرض السكري النوع الاول فضلا عن مجموعة السيطرة المكونة من 50 طفلا يبدون أصحاء ظاهريا لغرض التحري عن وجود أليلات الخطورة لمستضدات التطابق النسيجي- الصنف الثاني. تم قياس الفعالية الوظيفية للخلايا اللمفية بعد حضنها مع الفايروسات انفة الذكر. أظهرت النتائج انخفاضا غير معنويا في الفعالية الوظيفية للخلايا اللمفية كأستجابة للمشطر وكذلك بعد حضنها مع فايروس الكوكساكي النوع المصلي ب-5 وفايروس الحمة الغدية للانواع المصلية 3، 4, و 7 في الاطفال المرضى مقارنة بالاصحاء. ولكن هذا الانخفاض كان معنويا فقط عند استخدام فايروس شلل الاطفا ل .هناك زيادة معنوية في نسبة الاطفال الحاملين لاليلات الخطورة من الصنف الثاني مقارنة بالاصحاء HLA class II (-DR3, DR4, DQ2 and DQ3) antigens وهناك علاقة مباشرة وقوية بين الفعالية الوظيفية للخلايا اللمفية بعد حضنها مع المستضدات الفايروسية ومستضدات التطابق النسيجي , بينما كانت العلاقة ضعيفة مع المستضدات الاخرى HLA- DR4, HLA- DQ3HLA-DR; -DQ2. عموما كانت الاستجابة قليلة في الاطفال المرضى ولكن هناك زيادة محسوسة عند الاطفال الحاملين لاليلات التطابق النسيجي من النوع الثاني


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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