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

• Published in: Diabetes (New York, N.Y.) Vol. 48; no. 12; pp. 2309 - 2315
• Main Authors: Pupilli, C, Giannini, S, Marchetti, P, Lupi, R, Antonelli, A, Malavasi, F, Takasawa, S, Okamoto, H, Ferrannini, E
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.12.1999
• Subjects: ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Adult; Age of Onset; Antigens, CD - immunology; Antigens, Differentiation - immunology; Autoantibodies; Autoantibodies - blood; Autoantibodies - pharmacology; Biological and medical sciences; Cells, Cultured; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - immunology; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glutamate Decarboxylase - immunology; Health aspects; Humans; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - immunology; Islets of Langerhans - metabolism; Italy; Male; Medical sciences; Membrane Glycoproteins; Middle Aged; NAD+ Nucleosidase - immunology; Physiological aspects; Regression Analysis; White People; Italy; Endocrinopathy; Human; Immunopathology; Pancreatic hormone; Langerhans islet; Autoantibody; Autoimmune disease; Non insulin dependent diabetes; Insulin; Endocrine secretion; Insulin dependent diabetes; Caucasoid; Detection; Endocrine pancreas
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.48.12.2309

Autoantibodies to CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) in Caucasian patients with diabetes: effects on insulin release from human islets. C Pupilli , S Giannini , P Marchetti , R Lupi , A Antonelli , F Malavasi , S Takasawa , H Okamoto and E Ferrannini Department of Clinical Pathophysiology, University of Florence, Italy. Abstract The type II transmembrane glycoprotein CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) has been proposed as a mediator of insulin secretion from pancreatic beta-cells and as a candidate for autoimmune reactions in type 2 diabetes. We evaluated the presence of anti-CD38 autoantibodies in Caucasian patients with diabetes and investigated the effect of these antibodies on insulin secretion from isolated human pancreatic islets. The presence of 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 (chi2 = 15.9, P = 0.0003 vs. 1.3% of control subjects). No significant differences were observed in sex distribution, current age, 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 1 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) medium glucose concentrations was evaluated in isolated human pancreatic islets. Data are medians (interquartile range). The anti-CD38+ sera potentiated insulin release both at low [95 (64) vs. 23 (12) microU/ml of control incubations, respectively, P < 0.0001] and high [271 (336) vs. a control of 55 (37) microU/ml, respectively, P = 0.001] medium glucose concentrations, whereas the anti-CD38- sera did not. Furthermore, in the pooled data from all 36 tested sera, insulin levels in the islet incubation medium were 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 subjects. These autoantibodies exert a stimulatory effect on insulin secretion by cultured human islets. The role of this autoimmune reaction in the pathogenesis of diabetes remains to be elucidated.