Infections and Antineutrophil Cytoplasmic Antibodies: Triggering Mechanisms

The precise cause of the antineutrophil cytoplasmic antibodies (ANCA) autoimmunity is not known and is likely to be multifactorial. Infections may trigger formation of ANCA and a fraction of the patients with infection-triggered ANCA develop ANCA-associated vasculitis. Here we discuss some of the proposed mechanisms of ANCA formation during the course of infection. They include initiation of autoimmune response by microbial peptides that are complementary to autoantigens; epigenetic silencing and antigen complementarity leading to upregulation of autoantigen genes; molecular mimicry between bacterial and self-antigens; formation of neutrophil extracellular traps that stimulate immune processes including production of ANCA; and interaction of bacterial components with Toll-like receptors, which leads to formation of mediators affecting the immune responses to infections and can trigger ANCA production. Further work is needed to clarify these mechanisms and develop preventive measures and therapeutic interventions.