High concentrations of anti-caspase-8 antibodies in Chilean patients with type 1 diabetes

Abstract

Introduction: Deregulation of apoptosis across the Fas–FasL pathway is an increasingly relevant phenomenon in the pathogenic mechanisms associated with autoimmune diseases. Caspase-8 initiates the activation of the apoptotic process and interacts directly with Fas in the membrane of the T lymphocyte. Objectives: To standardize an Elisa essay to measure the concentration of anti-caspase-8 antibodies in plasma of Type 1 Diabetes (T1D) patients and analyze their possible distribution and association with characteristics of the disease. Methods and subjects: 124 patients newly diagnosed with T1D and 132 controls: children and youngsters. ELISA test was standardized to detect anti-caspase-8 antibodies in plasma. It correlated the concentration of this antibody with classical markers of autoimmunity as anti-IA-2 and anti-GAD65, and the clinical characteristics at onset of diabetes mellitus. The statistical analysis was performed using logistic regression. Results: Patients with T1D showed a higher concentration of anti-caspase-8 antibodies regarding the controls (87.5 ng/ml versus 24.3 ng/ml, p < 0.0001, values expressed as median). The proportion of patients with T1D and high concentrations of anti-caspase-8 (percentile 50–75) was significantly different from the control group (p < 0.0001). Anti-caspase-8 showed a strong association with positive anti-GAD65 (OR = 3.48, p < 0.035) and ketoacidosis (OR = 10.74, p < 0.0001) events, with glycemia and age at diagnosis as contributing variables. Conclusion: This is the first report in the literature of levels of anti-caspase-8 antibodies in T1D through ELISA. The high concentration in patients with T1D, and its strong correlation with anti-GAD65 autoantibodies, suggests a potential role of anti-caspase-8 auto-antibodies as surrogate marker autoimmunity in T1D patients.