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

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Abstract
Background 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. Material and methods 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. Results 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%). Conclusion 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.