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Evans Leaders Fund"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Sex Differ"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rheumatoid Arthritis (RA), a systemic autoimmune disorder of unknown etiology, disproportionately affects females at a 3:1 ratio compared to males. While biological sex differences in the immune system exist, sex-related differences in inflammatory and immune mediators of RA disease severity are undefined. Our objective was to characterize sex-related differences in immune responses in a murine collagen-induced arthritis (CIA) model and in human RA patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In CIA compared to saline control mice, inflammatory disease severity was assessed using standardized clinical scores. Anti-collagen antibodies, neutrophil elastase, calprotectin\/ S100A8\/A9 heterodimer, CRAMP, MMP3, and MMP9 were quantified by ELISA in the sera and joint tissues. Cytokine\/chemokine levels in sera and joints were assessed using a Luminex based-44-Plex Discovery Assay\n                      <jats:sup>\u00ae<\/jats:sup>\n                      Array. Immunophenotyping of mouse splenic T cells analysis was performed by flow cytometry. Proteomic profiling of serum samples from an established RA cohort (72 female and 19 male that were at least 84% ACPA+) was performed using an aptamer-based SomaScan platform.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified distinct sex-related differences in disease severity and pro-inflammatory profiles in the sera and joint tissues of CIA mice, with inflammatory responses that were male-skewed in the sera and female-skewed in the joints. Furthermore, we demonstrated heightened neutrophil activation markers and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell-mediated inflammatory responses in female CIA mice. Similar sex-related differences in neutrophil activation and leucocyte migration were identified in RA patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study demonstrates novel sex differences in pro-inflammatory mediators and activities of neutrophils and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells associated with disease severity in CIA mice, and in human RA patients. These findings provide new insights into sex-related differences in immunological pathways associated with inflammatory arthritis, which may contribute to the sex disparity in RA pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13293-026-00840-w","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T06:25:08Z","timestamp":1770445508000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sex differences in disease severity and immune responses in murine and human inflammatory arthritis"],"prefix":"10.1186","volume":"17","author":[{"given":"Mahadevappa","family":"Hemshekhar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam J","family":"O\u2019Neil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nyambura","family":"Kahia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney L.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamarah","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Navarrete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani","family":"El-Gabalawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeloffer","family":"Mookherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0220-0076","authenticated-orcid":false,"given":"Janilyn","family":"Arsenio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,7]]},"reference":[{"issue":"10055","key":"840_CR1","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","volume":"388","author":"JS Smolen","year":"2016","unstructured":"Smolen JS, Aletaha D, McInnes IB. 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