{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T19:17:31Z","timestamp":1783538251796,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CSL Behring Bern","award":["no. 108145"],"award-info":[{"award-number":["no. 108145"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Arthritis in K\/BxN mice is provoked by pathogenic autoantibodies to glucose-6-phosphate isomerase (G6PI), which is a ubiquitously expressed enzyme that is present in cells, in the circulation and on articular cartilage. When G6PI autoantibodies (auto-Abs) deposit on the articular cartilage of K\/BxN mice, arthritis ensues due to the activation of various components of the innate immune system. Recent studies have investigated the in vivo efficacy of recombinant fragment-crystallizable (Fc) protein-based therapeutics. Many recombinant Fc proteins evaluated provide protection against inflammation in mouse models of arthritis, such as the K\/BxN serum-transfer model. More recently, rFc-\u00b5TP-L309C, a recombinant human IgG1-Fc with an additional point mutation at position L309C fused to the human IgM tailpiece to form a hexamer, has been shown to ameliorate the arthritis in K\/BxN mice. Additional studies have shown that rFc-\u00b5TP-L309C has multiple effects that work together to ameliorate the arthritis, including inhibition of neutrophil migration into the joint, inhibition of IL-1\u03b2 production, downregulation of Th1 and Th17 cells, and increases in T regulatory cells and synovial fluid IL-10. In this work, rFc-\u00b5TP-L309C was shown to effectively prevent arthritis in the K\/BxN serum-transfer model, significantly downregulate inflammatory cytokines\/chemokines, and ameliorate the arthritis in the endogenous K\/BxN model. This amelioration of the arthritis was associated with a significant decrease in autoantibody levels, which was independent of the neonatal Fc receptor (FcRn). rFc-\u00b5TP-L309C was shown to specifically inhibit G6PI autoantibody secretion from B-cells with a concomitant increase in TGF\u03b2 and decrease in B-cell activating factor (BAFF). These new findings suggest that rFc-\u00b5TP-L309C may provide a therapeutic benefit for other antibody-mediated autoimmune diseases through its effects on B-cells.<\/jats:p>","DOI":"10.3390\/ijms27031277","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:41:56Z","timestamp":1769528516000},"page":"1277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Recombinant Human IgG1-Hexamer Reduces Pathogenic Autoantibodies in the K\/BxN Mouse Model of Arthritis Independent of FcRn"],"prefix":"10.3390","volume":"27","author":[{"given":"Bonnie J. B.","family":"Lewis","sequence":"first","affiliation":[{"name":"Centre for Innovation, Canadian Blood Services, Keenan Research Centre, 30 Bond Street, Toronto, ON M5B 1W8, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruqayyah J.","family":"Almizraq","sequence":"additional","affiliation":[{"name":"Centre for Innovation, Canadian Blood Services, Keenan Research Centre, 30 Bond Street, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selena","family":"Cen","sequence":"additional","affiliation":[{"name":"Centre for Innovation, Canadian Blood Services, Keenan Research Centre, 30 Bond Street, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Binnington","sequence":"additional","affiliation":[{"name":"Centre for Innovation, Canadian Blood Services, Keenan Research Centre, 30 Bond Street, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayluz","family":"Frias Boligan","sequence":"additional","affiliation":[{"name":"Centre for Innovation, Canadian Blood Services, Keenan Research Centre, 30 Bond Street, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Spirig","sequence":"additional","affiliation":[{"name":"CSL Behring Biologics Research Center, 3014 Bern, Switzerland"},{"name":"Swiss Institute for Translational and Entrepreneurial Medicine, sitem-insel, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4255-9350","authenticated-orcid":false,"given":"Fabian","family":"K\u00e4sermann","sequence":"additional","affiliation":[{"name":"CSL Behring Biologics Research Center, 3014 Bern, Switzerland"},{"name":"Swiss Institute for Translational and Entrepreneurial Medicine, sitem-insel, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6878-0563","authenticated-orcid":false,"given":"Shannon E.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, 2075 Bayview Street, North York, ON M4M 2M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8974-2451","authenticated-orcid":false,"given":"Donald R.","family":"Branch","sequence":"additional","affiliation":[{"name":"Centre for Innovation, Canadian Blood Services, Keenan Research Centre, 30 Bond Street, Toronto, ON M5B 1W8, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada"},{"name":"Department of Medicine, University of Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","first-page":"529","article-title":"Immune complexes in human diseases: A review","volume":"100","author":"Theofilopoulos","year":"1980","journal-title":"Am. 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