Circulating Reg1 alpha Proteins and Autoantibodies to Reg1 alpha Proteins as Biomarkers of beta-Cell Regeneration and Damage in Type 1 Diabetes

Type 1 diabetes is an autoimmune disease where beta-cells are in a constant process of death and renewal. Reg genes play a role in beta-cells regeneration. Reg proteins may be target of an autoimmune response in type 1 diabetes with consequent production of autoantibodies and failure of regeneration. The objective of this work was to characterize the role of Reg1 alpha proteins and anti-Reg1 alpha antibodies as biomarkers of beta-cell regeneration and damage. Serum levels of Reg1 alpha protein were investigated in 87 type 1 diabetic subjects (31 newly diagnosed and 56 long standing), 63 type 2 diabetic subjects, 39 subjects with systemic lupus erythematosus (SLE), a nonpancreatic autoimmune disorder, and 64 healthy subjects. The presence of anti-Reg1 alpha antibodies and correlation with metabolic, immune, and genetic parameters were analyzed in diabetic subjects. Increased levels of Reg1 alpha protein were observed in newly diagnosed (p = 0.002), and long standing (p = 0.001) type 1 diabetes patients and type 2 diabetic subjects (p < 0.001). Anti-Reg1 alpha antibodies were found in 47% of patients with type 1 diabetes. No correlation was found with metabolic, immune, and genetic parameters. Patients with SLE showed no increase in Reg1 alpha protein. We report here for the first time raised serum Reg1 alpha protein in type 1 and type 2 diabetes and anti-Reg1 alpha antibodies in type 1 diabetes. Reg1 alpha levels appear not to be influenced by genetic or metabolic control. These findings allow considering future studies on Reg1 alpha protein and autoantibody as new tools in the evaluation and monitoring of beta-cells regeneration and autoimmunity.