We found significantly elevated H3 citrullination in CD14 hi monocytes, as well as CD1c + dendritic cells and CD66 + granulocytes. Here, we analyzed 13 ACPA (+) subjects without arthritis but at-risk for future development of RA, 14 early RA patients, and 13 healthy controls. We aimed to explore H3 citrullination and cytokine/metabolomic signatures in peripheral blood immune cells from subjects prior to and after the onset of RA, at baseline and in response to ex vivo toll-like receptor (TLR) stimulation. However, the roles of H3 citrullination in other immune cells are not fully elucidated. Intracellular citrullination of H3 in neutrophils and T cells is known to regulate immune cell function by promoting neutrophil extracellular trap formation and citrullinated autoantigen release as well as regulating the Th2/Th17 T cell phenotypic balance. ACPA recognize multiple citrullinated proteins, including histone H3 (H3). ACPA are present in the peripheral blood for several years prior to the onset of arthritis and clinical classification of RA. The presence of anti-citrullinated protein/peptide antibodies (ACPA) and epitope spreading across the target autoantigens is a unique feature of rheumatoid arthritis (RA). 7 University of Colorado School of Medicine, Department of Immunology and Microbiology, Aurora, CO, USA University of Colorado School of Medicine, Children's Hospital Colorado, Department of Pediatrics, Section of Allergy & Immunology, Aurora, CO, USA.6 Colorado School of Public Health, Department of Epidemiology, Aurora, CO, USA.5 University of Colorado Denver, Division of Rheumatology, Aurora, CO, USA.4 University of Colorado School of Medicine, Department of Immunology and Microbiology, Aurora, CO, USA.3 University of Colorado Denver, Department of Medicine, Aurora, CO, USA.Electronic address: 2 Colorado School of Public Health, Department of Biostatistics and Informatics, Aurora, CO, USA. 1 University of Colorado Denver, Division of Rheumatology, Aurora, CO, USA Tokyo Women's Medical University School of Medicine, Department of Rheumatology, Tokyo, Japan.
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