{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T10:35:17Z","timestamp":1770460517410,"version":"3.49.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014717","name":"National Outstanding Youth Science Fund Project of National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>As a member of interleukin-12 family, interleukin-35 (IL-35) plays an important regulatory role in immune response. The relationship between IL-35 and idiopathic membranous nephropathy (IMN) is still unclear, and the purpose of this study is to clarify the relationship between IL-35 and disease activity and remission of IMN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study was a single-center, retrospective study in which all patients were diagnosed with IMN by renal biopsy or aPLA2R titer and treated with Mahuang Fuzi and Shenzhuo Decoction (MFSD). A follow-up was conducted with the endpoint of clinical complete or partial remission (CR+PR). Levels of serum IL-35 were measured and its relationship with IMN remission were analyzed. The regulatory T cell (Treg) and inducible IL-35 producing Tregs (iTR35) in peripheral blood of IMN patients were detected by flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 76 IMN patients (age 51.95 \u00b1 13.29) were followed-up for 18 (12, 24) months. The level of serum IL-35 in all patients increased after treatment, but the degree of increase in remission group was significantly higher than that in no remission (NR) group (117.6% <jats:italic>vs<\/jats:italic> 83.7%, <jats:italic>P<\/jats:italic>&amp;lt;0.01). The baseline IL-35 level in remission group was higher than that in NR group (174.87 <jats:italic>vs<\/jats:italic>.151.87 pg\/ml, <jats:italic>P<\/jats:italic>=0.016). Cox regression analysis showed that baseline IL-35 level was a independent risk factor for IMN remission (HR 1.081, 95%CI 1.048-1.116, <jats:italic>P<\/jats:italic>&amp;lt;0.001). Patients with baseline IL-35 lower than the lower quartile (\u2264145.49 pg\/ml) had an average remission time twice as long as those with baseline IL-35 higher than the upper quartile (&amp;gt; 203.05 pg\/ml) (12mon <jats:italic>vs<\/jats:italic>. 24mon, <jats:italic>P<\/jats:italic>&amp;lt;0.01). The baseline IL-35 can predict the remission time of IMN patients with either aPLA2R positive (AUC=0.673) or negative (AUC=0.745). Analysis of 18 patients with IMN showed that IL-35 level had a higher correlation with iTR35, but not Treg (r=0.613, <jats:italic>P<\/jats:italic>&amp;lt;0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The level of IL-35 in patients with IMN showed an increasing trend with the progress of treatment, and the baseline IL-35 could predict the remission time of IMN patients, including those patients with negative aPLA2R. The level of IL-35 is related to the number of iTR35 cells.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.926368","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T09:30:55Z","timestamp":1659432655000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Level of interleukin-35 in patients with idiopathic membranous nephropathy and its predictive value for remission 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