Systemic lupus erythematosus therapeutic strategy: From immunotherapy to gut microbiota modulation

Abstract

Systemic lupus erythematosus (SLE) is characterized by a systemic dysfunction of the innate and adaptive immune systems, leading to an attack on healthy tissues of the body. During the development of SLE, pathogenic features, such as the formation of autoantibodies to self-nuclear antigens, caused tissue damage including necrosis and fibrosis, with an increased expression of type Ⅰ interferon (IFN) regulated genes. Treatment of lupus with immunosuppressants and glucocorticoids, which are used as the standard therapy, is not effective enough and causes side effects. As an alternative, more effective immunotherapies have been developed, including monoclonal and bispecific antibodies that target B cells, T cells, co-stimulatory molecules, cytokines or their receptors, and signaling molecules. Encouraging results have been observed in clinical trials with some of these therapies. Furthermore, a chimeric antigen receptor T cells (CAR-T) therapy has emerged as the most effective, safe, and promising treatment option for SLE, as demonstrated by successful pilot studies. Additionally, emerging evidence suggests that gut microbiota dysbiosis may play a significant role in the severity of SLE, and the use of methods to normalize the gut microbiota, particularly fecal microbiota transplantation (FMT), opens up new opportunities for effective treatment of SLE.