Dysregulation of Immune System in Diabetic Child
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- Category: Vol. 77, June 2009
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Dysregulation of Immune System in Diabetic Child,EHAB A. ALBANNA, HALA EL-GENDY and NEHAD ABD EL-MONEM
Abstract
Introduction: Diabetes is a chronic disease associated with selective destruction of the pancreatic B-cells. The exact etiology of the disease is unclear; however, insulin deficiency results from autoimmune destruction of B-cells. The appear-ance of auto antibodies to beta cell antigen, such as those against the 65-KDA isoform of glutamic acid decarboxylase GAD65 and the protein tyrosine phosphates in the peripheral circulation is a predictive sign of clinical disease in non diabetic individuals. Although GAD65 and IA-2 (insulin auto antibodies) may not be directly involved in the pathogenic processes in beta-cell destruction. They are good markers in assessing the risk of disease manifestation.
Aim of the Work: This study aimed to evaluate GAD65 (glutamic acid decarboxylase) and ICA (islet cell auto anti-bodies) and IA-2 (insulin auto antibodies) auto antibodies as a disease markers and their relationship to certain residual beta-cell function and glycemic control in type I diabetes and risk group, and assess the relation between CD4+ CD25+ (T-regulatory cells) and immune mediated diabetes.
Patients and Methods: This study was conducted on 50 subjects randomly selected from those attending pediatrics outpatients clinics in the period of 2008. The subjects were classified into 3 groups: 1- Group A (patient group): This group included 20 patients diagnosed as type I DM according to WHO classifications. Their ages ranging from 3-16 years with a mean age of 10.6±4.0. They were 11 males and 9 females. 2- Group B: (Risk group): included 20 sibling of diabetic (type I DM) father, mother or both. They were 9 females and 11 males their ages ranging from 18 years to 25 years with a mean of age 21±2.5. 3- Group C: Control group, included 10 healthy children; they were 5 females and 5 males, their ages ranging from 5-16 years with a mean age of 10.8±2.8, with no family history of diabetes mellitus. All subjects are subjected to: Complete history taking, Full clinical examina-tion, Complete blood picture, Glycosylated Hb using ion-exchange chromatography, C-peptide of insulin by- ELISA, Determination of GAD 65, ICA and IA-2 auto antibodies by ELISA technique, Flowcytometric measurement of the expres-sion of the CD4+/CD25+ of T- regulatory cell.
Results: The most frequently encountered antibody in children group was GAD65 in 60% of cases, followed by
ICA, 40%. When taken together, both GAD65 and ICA were detected in 30%. IA-2 was detectable only in 30% of cases. When both GAD65 and IA-2 were taken together, they were detected in 25% of cases also ICA and IA-2 were detected in 15% of cases. When GAD, ICA and IA-2 were taken together, they were detectable in 5% of cases. The most frequently encountered antibody in risk group was ICA in 15% of cases, followed by GAD, in 10%. When taken together, both GAD65 and ICA were detected in 10%. IA-2 was detectable only in 10% of cases. When both GAD65 and IA-2 were taken to-gether, they were detected in 5% of cases also ICA and IA-2 were detected in 5% of cases. When GAD, ICA and IA-2 were taken together, they were detectable in 5% of cases. There was highly significant difference between 3 groups for prevalence of GAD65 autoantibody (p<0.001) and significant difference between 3 groups for prevalence of ICA autoanti-body (p<0.005) and significant difference between 3 groups for prevalence of IA-2 autoantibody (p<0.003). There were highly significant differences in the level of fasting C-peptide of insulin between patient and control groups. (p value <0.001). There were significant difference between level of fasting C-peptide and single and multiple autoantibody positivity (p<0.05). In the children group the mean and SD of the percentage of CD4+ CD25+ from CD4 cells were 0.96, 0.46 respectively. In the control group the mean and SD of the percentage of CD4+ CD25+ from CD4 cells were 2.85, 0.92 respectively. The difference between control and study group according to the mean and SD of the percentage of CD4+ CD25+ from CD4 cells was statistically highly significant (p<0.001). In the Risk group the mean and SD of the percentage of CD4+ CD25+ from CD4 cells were 0.99, 0.7 respectively.
In the control group the mean and SD of the percentage of CD4+ CD25+ from CD4 cells were 2.96, 0.62 respectively. The difference between control and risk group according to the mean and SD of the percentage of CD4+ CD25+ from CD4 cells was statistically non significant. There was highly sig relation (p<0.001) between percent of CD4+ CD25+ out of CD4 cells and the presence and absence of auto antibodies in the children group. There was no sig relation between percent of CD4+ CD25+ out of CD4 cells and the presence and absence of auto antibodies in the in risk group.
Conclusions: At the time of diagnosis almost all patients with type I diabetes have auto antibodies that are reactive to islet antigens and auto antibodies GAD, ICA, IA-2 are of value for predicting IDDM in sibling of diabetic parents type I also CD4+ CD25+ T-regulatory cells actively suppress activation of the immune system and prevent pathological self-reactivity.