IMMUNE CHECKPOINT INHIBITION AND AUTOIMMUNITY: RHEUMATOLOGICAL PROBLEMS

Abstract

The paper deals with the mechanisms of a T-cell immune response, which depends on the balance between costimulatory and coinhibitory signals that have been called as immune checkpoints (ICP). The imbalance of T-cell activation within ICTs (CTLA4/CD28 and PD1/PD1L) is considered to be a fundamental mechanism not only of autoimmune disease, but also impaired antitumor immunity underlying the development of malignant tumors. The use of monoclonal antibodies against negative regulatory ICTs (CTLA4, PD1, and PD1L) is a major achievement in the treatment of malignant neoplasms in the early 21st century. However, since CTLA4 and PD1 control the activation of auto-reactive T cells, the inhibition of these ICTs is associated with the development of autoimmune disease that is defined as immune-mediated adverse even. The paper considers the clinical manifestations of IMAR, primarily rheumatic ones and discusses the prospects of pharmacotherapy from the standpoint of achievements of modern rheumatology.

Keywords

• cytotoxic t-lymphocyte antigen 4 (ctla4), cd152
• programmed death-1 (pd1)
• immune-mediated adverse reactions (immune related adverse events)