Immunogenetic study and autoantibody status in type 1 diabetic patients and their siblings

العناوين الأخرى

دراسة جينية و مناعية و حالة الأضداد الذاتية في مرض السكري النمط الأول و إخوانهم

مقدم أطروحة جامعية

al-Rabii, Isra Ali Husayn

مشرف أطروحة جامعية

al-Suhail, Raghad G.
Adhiah, Ali Husayn

الجامعة

جامعة بغداد

الكلية

كلية العلوم

القسم الأكاديمي

قسم علوم الحياة

دولة الجامعة

العراق

الدرجة العلمية

ماجستير

تاريخ الدرجة العلمية

2010

الملخص الإنجليزي

The present study aimed to shed light on the association between HLAclass I antigens (A, B and Cw) and type 1 diabetes mellitus (T1DM), in the ground of their individual frequencies or two-locus association in patients and their sibs who were one year younger than the patients.

Blood group phenotypes (ABO system) were similarly evaluated.

Equally important, the serum level of anti-GAD (glutamic acid decarboxylase) and anti-IA-2 (tyrosine phosphatase) autoantibodies and C-peptide was assessed in terms of their means in patients or their sibs; furthermore, the impact of HLA antigens on these levels was also determined.

Finally, the viral aetiology of T1DM was targeted through the positivity of subject's sera for two anti-viral antibodies (anti-cytomegalovirus; CMV and anti-rubella). A total of 25 T1DM patients (12 males and 13 females) were enrolled in the study.

They were at the early onset of disease (less than four months); with an age range of 8-19 years at the time of investigation.

The patients were referred to the out-patient clinic of National Diabetes Centre, Al-Mustansiriyah University (Baghdad; January - March 2009) and Ibn Balady Hospital (Baghdad; March - June 2009) for diagnosis, treatment or follow-up evaluation. In addition to patients, further two groups of subjects were also investigated. The first included 25 sibs (15 males and 10 females) of patients, while the second group was represented by 25 apparently healthy subjects.

They were age (6-19 years), gender (13 males and 12 females) and ethnicity (Iraqi Arabs) matched with patients and their sibs. At HLA-A locus, antigens A1 (56.0 vs.

8.0%) and A10 (36.0 vs.

12.0%) showed a significant increased percentage in T1DM patients as compared to controls, while A11 was presented with a significant decreased percentage in the patients (4.0 vs.

24.0%), but a corrected significant level (Pc = 2.3 ×10-3) was maintained for A1 only.

Such antigen was also maintained a corrected Summary ___________________________________________________________________________ ii significant (Pc = 4.1×10-4) increased percentage (56.0 vs.

4.0%) in patients as compared to their sibs.

Comparing diabetic sibs with controls revealed variations in only one HLA-A antigen, which was A10 (40.0 vs.

12%), but the difference was significant before correcting the P value (P = 0.025).

At HLA-B locus, only antigen B35 showed an increased percentage frequency in T1DM patients as compared with controls (24.0 vs.

4%), and such difference was significant before correction (P = 0.049).

With respect to HLA-C locus, the T1DM patients showed no deviation in antigen frequencies as compared to controls, but the patient's sibs demonstrated increased frequencies of two antigens in comparison with controls; Cw1 (28.0 vs.

4.0%) and Cw2 (32.0 vs. 4%), and the differences were significant before correction (P = 0.024 and 0.012, respectively). With reference to HLA gene frequencies, T1DM patients were mainly characterized by the allele A*1 (gene frequency = 0.337) and accounted for more than 30% of the total pool of HLA-A alleles, while at HLA-B and -C loci, the corresponding alleles were B*12 and Cw*6 (0.152 and 0.226, respectively). The corresponding alleles in patient's sibs were A*10 (0.226), B*5, B*12 and B*17 (each with a gene frequency of 0.106) and Cw*4 (0.226), while they were A*19 (0.252), B*5 (0.226) and Cw*4 (0.106) in controls.

Two locus associations (expected or observed) between these alleles revealed different frequency distributions and each allelic combination variation was subjected to the investigated groups (patients, sibs or controls) and if it was expected or observed. Blood group (ABO system) revealed that T1DM patients were mainly presented with the phenotype O, which accounted for 44.0% of the cases, while patient's sibs were presented with the blood group A (52%), and in controls, blood groups A and O shared a similar frequency (32.0%).

However, the differences failed to attain any significant level (P > 0.05), wherever the Summary ___________________________________________________________________________ iii comparisons were made between the three investigated groups or between the observed and the expected frequencies. With respect to the serum level of autoantibodies and C-peptide, anti-GAD was significantly increased in the patients (51.66 IU/ml) as compared to the patient's sibs (5.44 IU/ml) or controls (5.49 IU/ml).

The anti-IA-2 antibody behaved in a similar manner (35.31 vs.

13.86 and 10.94 IU/ml, respectively), while C-peptide showed a different variation.

The C-peptide was significantly decreased in the patients and their sibs (9.65 and 6.55 ng/ml, respectively) as compared with controls (16.66 ng/ml).

These variations were also subjected to the impact of HLA antigens, as well as, the group under investigation.

In T1DM patients, B35 occupied 33% of the total serum level of anti-GAD antibody, while it had no effect in sibs or controls.

In anti-IA-2 autoantibody, B8 occupied 31% of the total serum level in T1DM patients, while HLA antigen profile of patient's sibs was presented by Cw2 and occupied 26%.

In controls, HLA antigens had no effect on anti-IA-2 antibody production.

With respect to Cpeptide each of the three investigated groups was presented with a different HLA antigen that occupied the highest percentage of the total C-peptide serum level.

It was Cw1 in T1DM patients (26%), A1 in patient's sibs (35%) and Cw2 in controls (35%). The assessment of anti-viral antibodies revealed that 28% of patient's sera were positive for anti-CMV antibody, while it was less frequent in patient's sibs or controls (12 and 8%, respectively).

Anti-rubella antibody positive cases shared the frequency of anti-CMV antibody in patients (28%), but the frequency was higher in patient's sibs (36%), while in controls, it was 16%.

التخصصات الرئيسية

الأحياء

عدد الصفحات

93

قائمة المحتويات

• APA
• MLA
• AMA

لغة النص

الإنجليزية

نوع البيانات

رسائل جامعية

رقم السجل

BIM-597338