{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:44:27Z","timestamp":1790034267201,"version":"4.0.1"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of immune tolerance, leading to systemic inflammation and organ damage. The <jats:italic>Mediterranean fever<\/jats:italic> (<jats:italic>MEFV<\/jats:italic>) gene, primarily linked to familial Mediterranean fever (FMF), has been suggested to have a protective role against SLE. However, comprehensive whole-exon analyses of <jats:italic>MEFV<\/jats:italic> and research on <jats:italic>MEFV<\/jats:italic> or FMF in non-Mediterranean populations, where <jats:italic>MEFV<\/jats:italic> exon 10 mutations are relatively rare, are limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a whole-exon analysis of the <jats:italic>MEFV<\/jats:italic> gene in 55 Japanese patients with SLE. Patients were classified based on the presence or absence of <jats:italic>MEFV<\/jats:italic> variants, and their clinical characteristics were compared. In addition, we generated MRL\/lpr mice with the human <jats:italic>MEFV<\/jats:italic> E148Q variant using CRISPR technology to examine its impact on disease phenotypes. Disease activity and kidney pathology were assessed using the established clinical and histological scoring systems.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 55 patients, those carrying <jats:italic>MEFV<\/jats:italic> variants exhibited a significantly lower prevalence of lupus nephritis than non-carriers (P = 0.007). The number of <jats:italic>MEFV<\/jats:italic> variants was inversely associated with the risk of lupus nephritis (P = 0.03). In MRL\/lpr mice, the E148Q variant was associated with reduced anti-dsDNA antibody production, reduced formation of memory B cells, and milder kidney pathology, indicating a shift from adaptive immunity to innate immune responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that <jats:italic>MEFV<\/jats:italic> variants, particularly the E148Q variant, may play a protective role against lupus nephritis in Japanese patients with SLE by modulating immune responses. These results provide valuable insights into the genetic factors influencing SLE severity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1571208","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T16:45:49Z","timestamp":1751906749000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Mediterranean fever gene variants may prevent the development of lupus nephritis in Japanese patients with systemic lupus 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