Egypt J Pediatr Allergy Immunol, (October 2008), Volume No. 6, Issue 02  
Egypt J Pediatr Allergy Immunol 2008 ; 6 ( 02 ) : 57-67 -
, ESP - 74  
Lymphocyte apoptosis in the pathogenesis of type 1 diabetes mellitus
Eman M. Sherif   Amira A.M. Adly   Hala G. Mohamed   Ali Ahmed      
Background: Beta cell apoptosis has been associated with insulin dependent diabetes mellitus (IDDM) onset in newly diagnosed diabetic patients. There is an emerging evidence that T cell-induced apoptosis is a dominant effector mechanism in diabetes mellitus type 1 (DM1). Pancreatic ?-cells derived from newly diagnosed type 1 diabetics were found to have increased cell surface expression of Fas (CD95) compared to ?-cells from healthy subjects. Objective: The study investigates the spontaneous lymphocyte apoptosis via CD95 molecule expression to demonstrate activation induced cell death in children with high risk of DM1 and in type 1 diabetics under insulin therapy. Methods: This study comprised 90 children and adolescents, divided into 3 groups. G(1) comprised 40 type-1 diabetics, their ages ranging from 8.0 to 17.0 years and disease duration between 2.0 and 12.0 years. G(2) (prediabetics) included 30 euglycaemic subjects who were first degree relatives of type 1 diabetics, with normal fasting blood glucose and positive first phase insulin release (FPIR) and/or positive islet cell (ICA) or glutamic acid decarboxylase (GAD) antibodies. G(3) comprised 20 healthy, age and sex matched subjects with no clinical or laboratory signs or family history of type-1DM. Patients were subjected to clinical evaluation with special emphasis on signs suggestive of microvascular complications. The study measurements included random blood sugar (RBS), glycosylated hemoglobin (HbA1c), urinary microalbumin assay and flow cytometric assessment of apoptosis by measuring CD95 percentage expression on CD3 lymphocytes. Results: The percentage of CD95 positive T-lymphocytes was significantly higher in prediabetics than in type-1 diabetics and controls (57.6876.68, 45.016.648,16.754.98% respectively; p<0.001). CD3 positive lymphocytes were significantly lower in prediabetics than type-1 diabetics and controls (52.9311.64, 66.237.04, 63.9103.4% respectively; p<0.001). The percentage of CD95 on T-lymphocytes could not be correlated with age, insulin dose and RBS, but HbA1c was positively correlated with both CD3 lymphocytes and CD95% expression. Complicated type-1 diabetics showed higher CD95% expression compared to noncomplicated patients. Conclusion: Peripheral blood lymphocytes with CD95 antigen expression are increased in prediabetics. As CD95 is an important receptor for activation-induced cell death, CD95 mediated apoptosis could play a potential role in the pathogenesis of DM1.