Contrasting cellular and humoral autoimmunity associated with latent autoimmune diabetes in adults

Abstract

Diabetes is clinically classified into two types: type 1 (T1D) and type 2 diabetes (T2D). Nevertheless, intermediate forms of diabetes are frequent and difficult to recognize and manage appropriately. In this study, we investigated whether patients with intermediate form of diabetes, here called unclassified diabetes (UD), have beta-cell autoimmune markers. beta-cell autoimmune markers (beta-cell autoantibodies (aAb), peripheral blood mononuclear cells (PBMC) responsive to five islet proteins, cytokine secretion, and human leukocyte antigen (HLA)-DQB1 genotypes) were analyzed in 50 UD patients, 23 age- and HLA-matched normal control subjects, and 23 classic T2D patients. We observed that 16 out of 50 (32%) UD patients demonstrated responsive PBMCs, as opposed to 1 out of 23 (5%) age- and HLA-matched normal control subjects, and 0 out of 23 classic T2D patients. Overall, 29 (58%) UD patients had at least one marker of beta-cell autoimmunity (beta-cell aAb and/or PBMC autoreactivity), in association with high-risk HLA genotypes DQB1*0201 and/or DQB1*0302. Moreover, the 13 (26%) UD patients who had beta-cell aAb were not the same as those with PBMC autoreactivity, except for one patient. Patients with PBMC autoreactivity were older at the onset of the disease and had a better residual beta-cell function than those with beta-cell aAb. Our data confirm that T-cell autoimmunity can be detected in latent autoimmune diabetes in adults patients. We show an inverse correlation between humoral and cellular beta-cell autoimmunities. Possible protective cellular responses in the patients with beta-cell PBMC autoreactivity could have potential therapeutic implications.