Lupus patients carry mutated immune cells that may trigger self-attacks

Researchers have discovered that lupus patients carry unusual mutations in immune cells called neutrophils, which may trigger the immune system to attack the body's own tissues, potentially driving inflammation and symptoms like joint pain. The findings, published in Nature, come from a joint study by La Jolla Institute for Immunology and the University of Washington. The study examined blood samples from 34 patients with systemic lupus erythematosus, finding splicing mutations in neutrophils from 33 of them, mutations absent in healthy volunteers. These mutations produced foreign-looking peptides, or neoantigens, that T cells and B cells recognized as threats, prompting an immune attack against the mutated cells. The researchers cannot confirm whether these mutations cause lupus or result from existing inflammation, but the findings support the "neoantigen hypothesis" of autoimmunity, suggesting the immune system may function normally while targeting unfortunate antigens. This offers a new perspective on neutrophil roles in lupus and potential treatment avenues.