{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:49:08Z","timestamp":1790480948401,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,9,28]],"date-time":"2012-09-28T00:00:00Z","timestamp":1348790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Spondylarthritides (SpA), including ankylosing spondylitis (AS), are common inflammatory rheumatic diseases that are strongly associated with positivity for the HLA class I allotype B27. HLA\u2013B27 normally forms complexes with \u03b2<jats:sub>2<\/jats:sub>\u2010microglobulin (\u03b2<jats:sub>2<\/jats:sub>m) and peptide to form heterotrimers. However, an unusual characteristic of HLA\u2013B27 is its ability to form \u03b2<jats:sub>2<\/jats:sub>m\u2010free heavy chain homodimers (HLA\u2013B27<jats:sub>2<\/jats:sub>), which, unlike classic HLA\u2013B27, bind to killer cell immunoglobulin\u2010like receptor 3DL2 (KIR\u20103DL2). Binding of HLA\u2013B27<jats:sub>2<\/jats:sub> to KIR\u20103DL2\u2013positive CD4+ T and natural killer (NK) cells stimulates cell survival and modulates cytokine production. This study was undertaken to produce an antibody to HLA\u2013B27<jats:sub>2<\/jats:sub> in order to confirm its expression in SpA and to inhibit its proinflammatory properties.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated monoclonal antibodies by screening a human phage display library positively against B27<jats:sub>2<\/jats:sub> and negatively against B27 heterotrimers. Specificity was tested by enzyme\u2010linked immunosorbent assay (ELISA), surface plasmon resonance (SPR) assay, and fluorescence\u2010activated cell sorting (FACS) analysis of B27<jats:sub>2<\/jats:sub>\u2010expressing cell lines and peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from patients with SpA. Functional inhibition of KIR\u20103DL2\u2013B27<jats:sub>2<\/jats:sub> interactions was tested using cell lines and PBMCs from patients with SpA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Monoclonal antibody HD6 specifically recognized recombinant HLA\u2013B27<jats:sub>2<\/jats:sub> by ELISA and by SPR assay. HD6 bound to cell lines expressing B27<jats:sub>2<\/jats:sub>. FACS revealed binding of HD6 to PBMCs and SFMCs from patients with AS but not from controls. HD6 inhibited both the binding of HLA\u2013B27<jats:sub>2<\/jats:sub> to KIR\u20103DL2 and the survival and proliferation of KIR\u20103DL2\u2013positive NK cells. Finally, HD6 inhibited production of the proinflammatory disease\u2013associated cytokine interleukin\u201017 by PBMCs from patients with AS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results demonstrate that antibody HD6 has potential for use in both the investigation and the treatment of AS and other B27\u2010associated spondylarthritides.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34538","type":"journal-article","created":{"date-parts":[[2012,5,10]],"date-time":"2012-05-10T18:46:05Z","timestamp":1336675565000},"page":"3139-3149","source":"Crossref","is-referenced-by-count":49,"title":["Inhibiting HLA\u2013B27 homodimer\u2013driven immune cell inflammation in spondylarthritis"],"prefix":"10.1002","volume":"64","author":[{"given":"Sravan 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