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Article
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
Association between HLA-Class II Alleles and T-Cell Proliferation in Response to Enterovirus and Adenovirus

Author: Eman M. Saleh
Journal: Iraqi Academic Scientific Journal المجلة العراقية للاختصاصات الطبية ISSN: 16088360 Year: 2007 Volume: 6 Issue: 2 Pages: 102-108
Publisher: The Iraqi Borad for Medical Specialization المجلس العراقي للاختصاصات الطبية

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Abstract

BACK GROUND:Viruses may be involved in the pathogenesis of Type 1 Diabetes Mellitus (T1DM), either through direct β-cell infection or as triggers of autoimmunity.OBJECTIVE:To evaluate the T- cell proliferation in response to Enterovirus antigens including Coxsackievirus B and Poliovirus in addition to Adenovirus in an HLA- matched population of children with T1DM and children who were healthy.METHODS:A total of 60 Iraqi T1DM children were included in the presents study. They were new onset of the disease. For the purpose of comparisons, 50 apparently healthy control subjects were 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 Poliovaccin.RESULTS & CONCLUSION: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


Article
Investigation of Circulating anti- Coxsackie B, anti- Polio and anti- Adeno IgG in newly diagnosed 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: 477-481
Publisher: Baghdad University جامعة بغداد

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Abstract

Back ground: Viruses may be involved in the pathogenesis of Type 1 Diabetes Mellitus (T1DM), either through direct β-cell infection or as triggers of autoimmunity. Objective: To investigate the presence of specific anti- viral IgG antibodies for Coxsackie virus type B (CVB5), Poliovirus, and Adenovirus which proposed to be involved in the etiology of T1DM. Subjects & methods: A total of 60 Iraqi T1DM children were included in the presents study. They were new onset of the disease (diagnosis was from one week up to five months). For the purpose of comparisons, 50 apparently healthy control subjects were selected. Serum IgG against Coxsackie virus type B5, Adenovirus type 3, 4, and 7, and Poliovaccin Trivalent were detected quantitatively with an indirect ELISA. Results: High proportion of anti-CVB5 IgG (20%)(p<0.05) and anti- Polio IgG (31.67%) were found in T1DM children compared to controls (8%, 26% respectively), while anti- Adeno IgG were detected in diabetic patients only (6.67%)(p<1.0001).


Article
HLA-CLASS II RISK ALLELES CONTROL T-LYMPHOCYTE PROLIFERATION IN RESPONSE TO ENTEROVIRUS AND ADENOVIRUS ANTIGENS AND IgG ANTIBODY PREVALENCE IN NEWLY DIAGNOSED T1DM CHILDREN
دور اليلات الخطورة لنظام مستضدات خلايا الدم البيض البشرية- الصنف الثانى فى استجابة الخلايا اللمفية ضد مستضدات الحمات المعوية والغدية وتفشى اضداد IgG هذه المستضدات في الأطفال المشخصين حديثاًبمرض السكر من النوع الأول

Authors: Nidhal abdul Mohymen نضال عبد المهيمن --- Eman M. Saleh إيمان مهدي صالح
Journal: IRAQI JOURNAL OF MEDICAL SCIENCES المجلة العراقية للعلوم الطبية ISSN: P16816579,E22244719 Year: 2007 Volume: 5 Issue: 3 Pages: 47-56
Publisher: Al-Nahrain University جامعة النهرين

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Abstract

Background: Viral infections are implicated in the pathogenesis of type 1 diabetes mellitus (T1DM) in a number of studies, and playing a role in the initiation of beta-cell damaging process.Objective: To evaluate the T- cell proliferation in response to enterovirus antigens including coxsackievirus B and poliovirus in addition to adenovirus in an HLA- matched population of children with T1DM and children who were healthy, in addition to screening for specific anti-viral IgG antibodies.Subjects and methods: A total of 60 Iraqi T1DM children were included in the presents study. They were newly diagnosed diabetics. For the purpose of comparisons, 50 apparently healthy children were selected. HLA typing was measured by microlymphocytotoxicity, while MTT assay was used for lymphocyte proliferation by culturing peripheral blood lymphocytes (PBLs) with Con-A, Coxsackievirus B5 (CVB5), Adenovirus 3, 4, and 7 serotypes, and Poliovaccine. Serum IgG against these viruses were detected quantitatively with an indirect ELISA.Results & conclusion: 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. Strong T-cell proliferation in response to the tested viral antigens were observed and was 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. High significant mean proliferative percentage for all tested viruses were detected in those patients who were sero-positive IgG as compared to the sero-negative IgG diabetic children.Conclusion: In children with new- onset diabetes, responses were generally decreased, but higher in children who carried risk HLA- class II alleles and who were sero positive to anti- viral IgG antibodies.Key Words: T1DM, HLA class II alleles, Lymphocyte proliferation, Anti- CVB5 IgG, Anti- polio IgG, Anti-adeno IgG.

خلفية الدراسة: أثبتت العديد من الدراسات أن للفايروسات دورا تؤديه في إحداث أمراضية مرض السكر من النوع الأول وقد يكون لها دوراً في بدء عملية تحطيم خلايا بيتا في البنكرياس.هدف الدراسة: الهدف من الدراسة هو لتقييم الفعالية الوظيفية للخلايا اللمفية بعد تحفيزها بمستضدات الحمات المعوية والتي تشمل فايروس الكوكساكي نوعB- (CVB) وفايروس شلل الأطفال فضلاً عن ألحمة الغدية (Adenovirus) في مجموعة من الأطفال المصابين بمرض السكري من النوع الأول ومجموع من الأطفال الأصحاء المطابقين لمستضدات التطابق النسيجي (HLA) من الصنف الثاني فضلاً عن التقصي عن وجود الكلوبيولينات المناعية نوعIgG ضد هذه الفايروسات.طريقة العمل: شملت الدراسة ستون مريضاً حديثي الإصابة بمرض السكري النوع الأول (مشخصين بالإصابة خلال فترة أقل من خمسة أشهر).والذين تم اختيارهم من المركز الوطني للسكري / الجامعة المستنصرية للفترة من مايس 2004 ولغاية تشرين الأول 2005. ولغرض المقارنة تم اختيار مجموعة من الأطفال (50) طفلاً الاصحاء ظاهريا لغرض التحري عن وجود اليلات الخطورة لمستضدات التطابق النسيجي – الصنف الثاني ثم قياس الفعالية الوظيفية للخلايا اللمفية بعد حضنها مع الفايروسات المذكورة سابقاً باستخدام طريقة MTT فضلاً عن قياس المستويات المصلية للكلوبيولين المناعي IgG ضد الفايروسات الثلاثة باستخدام طريقة ELISA الغير مباشرة .النتائج: أظهرت الدراسة الحالية انخفاضاً غير معنوياً في الفعالية الوظيفية للخلايا اللمفية كاستجابة للمشطر Con-A وكذلك باستخدام فايروس CVB النوع المصلي (5) وفايروس الـ Adenoللانواع المصلية 3 ، 4 و 7 في الأطفال المرضى مقارنة بالأصحاء. ولكن هذا الانخفاض كان معنوياً فقط عند استخدام فايروس شلل الأطفال (P < 0.05). وكانت الزيادة في الفعالية الوظيفية للخلايا اللمفاوية معنوياً (P < 0.05) عند المرضى الحاملين للاليلات الخطورة من الصنف الثاني HLA-DR3 ; - DR4 ; - DQ2 ; - DQ3 مقارنة بالمرضى الحاملين للاليلات الأخرى وكذلك عند المرضى الموجبين للكلوبيولينات المناعية نوع IgG مقارنة بالمرض السالبين .الاستنتاج: انخفضت الاستجابة المناعية عموماً في الأطفال المصابين ولكنها ازدادت في الأطفال الحاملين للاليلات الخطورة HLA من الصنف الثاني و الموجبين للكلوبيولينات المناعية نوع IgG المضادة للفايروسات.مفاتيح الكلمات: مرض السكر من النوع الأول ، مستضدات التطابق النسيجي - الصنف الثاني ، الفعالية الوظيفية للخلايا اللمفية ، الكلوبيولينات المناعية نوع IgG ضد فايروس الكوكساكي B النوع المصلي 5 وشلل الأطفال والحمى الغدية.

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