Just Autoimmunity? The Role of the Innate Immune Response in Lupus

• Published in: Journal of clinical rheumatology Vol. 31; no. 2; p. 71
• Main Authors: Rodriguez, Martin A, Blasini, Ana M
• Format: Journal Article
• Language: English
• Published: United States 01.03.2025
• Subjects: Autoantibodies - immunology; Autoimmunity - immunology; Humans; Immunity, Innate - immunology; Lupus Erythematosus, Systemic - immunology
• DOI: 10.1097/RHU.0000000000002209

Systemic lupus erythematosus is considered a prototype of human autoimmune disease based on the appearance of multiple autoantibodies, some of which can have a direct pathogenic effect on tissues. Most therapeutic modalities aim to check the enhanced humoral responses by targeting T and B cells with conventional or biologic drugs. However, in some cases, the clinical response is limited and frequently takes a high toll of toxicity in patients. The last 2 decades have brought up novel discoveries showing profound disturbances of innate immune cell function in systemic lupus erythematosus, including dysregulated NETosis, increased apoptosis, type 1 interferon, and granulopoiesis signatures that are grounded in basic cell biology abnormalities, including response to excessive oxidative stress, mitochondrial dysfunction, and upregulation of the cGAS-STING pathway. Whether the prominent autoimmunity component of lupus patients is sufficient to drive this chronic disease or follows a breakdown of innate immune homeostasis in response to the environmental factors triggering disease is the subject of this revision.