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


OBJECTIVE
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
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.


CONCLUSIONS
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 auto-antibodies, suggests a potential role of anti-caspase-8 auto-antibodies as surrogate marker autoimmunity in T1D patients.
Oyarzún
Amaya
A
Laboratory of Nutritional Genomics, Department of Nutrition, Faculty of Medicine, University of Chile, Independencia, Santiago, Chile.
Lera
Lydia
L
Codner
Ethel
E
Carrasco
Elena
E
Pérez-Bravo
Francisco
F
D000293:Adolescent; D000906:Antibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D053181:Caspase 8 / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002677:Chile; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000276:immunology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards; D000939:Epitopes; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007662:Ketosis; D008297:Male
D000906:Antibodies; D015415:Biomarkers; D000939:Epitopes; D053181:Caspase 8; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2