Autoantibodies to CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) in Caucasian patients with diabetes - Effects on insulin release from human islets

The type II transmembrane glycoprotein CD38 (ADP-ribosyl cyclase/cyclic ADP -ribose hydrolase) has been proposed as a mediator of insulin secretion fro m pancreatic beta-cells and as a candidate for autoimmune reactions in tape 2 diabetes. We evaluated the presence of anti-CD38 autoantibodies in Cauca sian patients with diabetes and investigated the effect of these antibodies on insulin secretion from isolated human pancreatic islets. The presence o f anti-CD38 autoantibodies was evaluated by using Western blot analysis in 236 patients with type 2 diabetes (mean age 63 years), in 160 patients with type 1 diabetes (mean age 38 years), and in 159 nondiabetic subjects. Anti -CD38 autoantibody titers at least 3 SD above the mean value of the control group were found in 9.7%, of type 2 diabetic patients and in 13.1% of type 1 diabetic patients (chi(2) = 15.9, P = 0.0003 vs. 1.3% of control subject s). No significant differences were observed in sex distribution, current a ge, age at diabetes onset, BMI, fasting serum glucose, or glycemic control between anti-CD38(+) and anti-CD38(-) diabetic patients in either the type 2 or type I diabetic groups. The effect of 23 anti-CD38(-) and 13 anti-CD38 (+) sera on insulin secretion at low (3.3 mmol/l) or high (16.7 mmol/l) med ium glucose concentrations was evaluated in isolated human pancreatic islet s. Data are medians (interquartile range). The anti-CD38(+) sera potentiate d insulin release both at low [95 (64) vs. 23 (12) mu U/ml of control incub ations, respectively, P < 0.0001] and high [271 (336) vs, a control of 55 ( 37) mu U/ml, respectively, P = 0.001] medium glucose concentrations, wherea s the anti-CD38(-) sera did not. Furthermore, in the pooled data from all 3 6 tested sera, insulin levels in the islet incubation medium mere directly related to the anti-CD38 antibody titer. We conclude that autoantibodies to CD38 are associated with both type 1 and type 2 diabetes in Caucasian subj ects. These autoantibodies exert a stimulatory effect on insulin secretion by cultured human islets. The role of this autoimmune reaction in the patho genesis of diabetes remains to be elucidated.