Evolving understandings for the roles of CD38 protein in autoimmunity and autoimmune disease

Autoimmune diseases are chronic idiopathic disorders characterized by inflammatory responses. Cluster of differentiation 38 (CD38), a surface molecule with enzymatic and signalling capabilities, contributes to the regulation of NAD+ metabolism and mediates various intracellular pathways. Recent research has revealed the influence of the CD38 protein in the pathogenesis of autoimmune diseases. During inflammation, CD38 is involved in regulating biological processes such as cell recruitment, cell activation, cytokine and chemokine release, antigen presentation, and phagocytosis. Dysfunctional CD38 induces autoimmune diseases. CD38 is expressed at low levels in various haematopoietic systems and tissues but exhibits elevated expression in multiple myeloma and plasma cells. CD38-targeted monoclonal antibodies with favourable therapeutic effects have been discovered, such as isatuximab, daratumumab, and mezagitamab. Although CD38-targeted antibodies were originally developed to eliminate malignant immune cells and inhibit their strong activation, these monoclonal antibodies can also inhibit autoantibodies production in autoimmune diseases. CD38 protein is a promising biomarker of autoimmune disease diagnosis and a potential therapeutic target for the treatment of autoimmune diseases. In this review article, we will focus on the latest findings on the involvement of CD38 in autoimmunity and autoimmune disease and assess the value of research and therapeutic application of CD38 in disease control.