Autoantibodies to REG, a beta‐cell regeneration factor, in diabetic patients

Abstract

Regenerating gene (Reg) product, Reg, acts as an autocrine/paracrine growth factor for beta-cell regeneration. The presence of autoimmunity against REG may affect the operative of the regenerative mechanisms in beta cells of Type 1 and Type 2 diabetes patients. We screened sera from Type 1 and Type 2 diabetes subjects for anti-REG autoantibodies, searched for correlations in the general characteristics of the subjects with the presence of anti-REG autoimmunity, and tested the attenuation of REG-induced beta-cell proliferation by the autoanitibodies. We examined the occurrence of anti-REG autoantibodies in patients' sera (265 Type 1, 368 Type 2 diabetes patients, and 75 unrelated control subjects) by Western blot analysis, and evaluated inhibitory effects of the sera on REG-stimulated beta-cell proliferation by a 5'-Bromo-2'-deoxyuridine (BrdU) incorporation assay in vitro. Anti-REG autoantibodies were found in 24.9% of Type 1, 14.9% of Type 2 and 2.7% of control subjects (P = 0.0004). There were significant differences between the autoantibody positive and negative groups in the duration of disease in the Type 1 subjects (P = 0.0035), and the age of onset in the Type 2 subjects (P = 0.0274). The patient sera containing anti-REG autoantibodies significantly attenuated the BrdU incorporation by REG (35.6 +/- 4.06% of the control), whereas the nondiabetic sera without anti-REG autoantibodies scarcely reduced the incorporation (88.8 +/- 5.10%). Anti-REG autoantibodies, which retard beta-cell proliferation in vitro, are found in some diabetic patients. Thus, autoimmunity to REG may be associated with the development/acceleration of diabetes in at least some patients.