ABSTRACT
The aim of this study was identification of cut off points of positivity of different antibodies [Ab] against islet cell antigens [ICA, Anti GAD Ab, Anti IA2 Ab] in Egyptian children and adolescents who are sibs of patients with type 1 diabetes as well as determination of their insulin secretory capacity and identification of HLA-DQB1 alleles known to predispose to or protected against type 1 diabetes. The ultimate aim is to identify those at high-risk of the disease to enroll them in preventive trials. This study was a longitudinal one that lasted for five years and include seventy-two sibs of type 1 diabetic patients recruited from the Diabetic Endocrine Metabolic Pediatric Unit [DEMPU] at Cairo University Children's Hospital. Thirty sex healthy subjects; age and sex matched with patients and with negative family history of autoimmune diseases were included as controls. Serum samples from all subjects and controls were analyzed for GAD[65], IA2 Ab using radioimmunoassay and ICA Ab using ELISA technique. Sibs who were positive for one or more Ab were further subjected to the assessment of first phase insulin response and HLA studies for detecting DQB1 alleles known to predispose or protect against type 1diabetes using SSP DNA-based technique. The results showed that 36 sibs [50%] were GADAb positive, 10 sibs [13.9%] were IA2 Ab positive while 14 sibs [19.4%] were ICA positive with overlap. Mean FPIR in 41 sibs positive for one or multiple Ab was 41.407 mU/L +/- 28.73 which was statistically significantly less than that in controls 79.414 mUL +/- 44.316 [P<0.001]. Thirty-four sibs [38%] lied in the high-risk group defined by FPIR less than 5[th] percentile. HLA studies done in 32 sibs showed that 17/32 sibs [54.84%] had the predisposing alleles DQB1 [0201, 0202, 0302, 0303, 0401] while 7 sibs [22.28%] had protective alleles DQB1 [0301, 0601]. Prevention of type 1diabetes will require reliable methods for early diagnosis of predisposition to the disease, using improved genetic and serological screening on a side scale and identification of the primary antigenic target[s] for specific tolerance. Those at risk [multiple positive antibodies and reduced insulin secretory response] in absence of HLA protective alleles are to be enrolled in preventive trials