Tu121 - Emergence of HLA-DR+ CD15+ ‘hybrid’ Cells in Active Rheumatoid Arthritis (RA)

Robert Winchester, Rheumatologist – Professor of Medicine, Division of Rheumatology, Columbia University Irving Medical Center; Christian Geier, Rheumatologist – Assistant Professor of Medicine, Rheumatology & Clinical Immunology, SUNY Upstate Medical University

Abstract Text: Most rheumatoid arthritis (RA) patients carry a particular ‘shared’ sequence of the HLA-DRB1 beta chain, implicating antigen presentation by HLA-DR as a key pathogenic mechanism in this inflammatory disease. We developed a gating strategy (Cytek Aurora) to comprehensively profile blood HLA-DR+ cells (isolated by Ficoll density centrifugation) in RA. Spectral cytometry showed a marked increase in HLA-DR positive cells resembling low-density neutrophils (LDN, CD15+CD16+CCR3-). The same cells also expressed CD303, traditionally associated with plasmacytoid dendritic cells (pDC). In contrast, CD123, expected in pDC, was undetectable, supporting that these cells are not simply LDN or pDCs but instead are better conceptualized as ‘hybrid’ cells. Successful RA treatment reduced ‘hybrid’ cells to negligible levels, whereas in treatment-resistant RA they remained much higher than in healthy donors. ‘Hybrid’ cells from patients with high disease activity formed a dominant HLA-DR+ cluster in active RA, which — along with very high levels of CD303 — co-expressed CD83 and CD275 (ICOS-L). The emergence of HLA-DR+CD15+ ‘hybrid’ cells in active RA highlights the potential clinical relevance of these cells that — given their expression of CD15 — may be of myeloid origin. Their simultaneous expression of CD303 and HLA-DR suggests that the cells may be involved in the capture and ultimate presentation of RA self-antigen. Their expression of ICOS-L (CD275) and CD83 lends support for potentially pro-inflammatory co-stimulation. Subsequent studies, aimed to confirm these functional characteristics, are pending.