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

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...

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Bibliographic Details
Published inJournal of clinical rheumatology Vol. 31; no. 2; p. 71
Main Authors Rodriguez, Martin A, Blasini, Ana M
Format Journal Article
LanguageEnglish
Published United States 01.03.2025
Subjects
Autoantibodies - immunology
Autoimmunity - immunology
Humans
Immunity, Innate - immunology
Lupus Erythematosus, Systemic - immunology
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Summary: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.
ISSN:1536-7355
DOI:10.1097/RHU.0000000000002209