Antigen-specific immunotherapies in type 1 diabetes

Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by the destruction of pancreatic beta cells, in which immune system disorder plays an important role. Finding a cure for T1DM and restoring beta cell function has been a long-standing goal. Research has shown that immune regulation with pancreatic islet auto-antigens may be the most specific and safe treatment for T1DM. Immunological intervention using diabetogenic auto-antigens as a target can help identify T1DM in high-risk individuals by early screening of autoantibodies (AAbs) before the loss of pancreatic islet function and thus achieve primary prevention of T1DM. However, induction of self-tolerance in patients with pre-diabetes can also slow down the attack of autoimmunity, and achieve secondary prevention. Antigen-based immune therapy opens up new avenues for the prevention and treatment of T1DM. The zinc transporter 8 (ZnT8) protein, presents in the serum of pre-diabetic and diabetic patients, is immunogenic and can cause T1D autoimmune responses. ZnT8 has become a potential target of humoral autoimmunity; it is of great significance for the early diagnosis of T1D. ZnT8-specific CD8⁺ T cells can be detected in most T1DM patients, and play a key role in the progression of T1D. As an immunotherapy target, it can improve the dysfunction of beta cells in T1DM and provide new ideas for the treatment of T1D. In this review, we summarize research surrounding antigen-specific immunotherapies (ASI) over the past 10 years and the ZnT8 antigen as an autoimmune target to induce self-tolerance for T1DM.

Keywords: Antigen-specific immunotherapies; Immune tolerance; Prevention; Type 1 diabetes mellitus; ZnT8.