Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis
Author:
Inamo JunORCID, Keegan Joshua, Griffith Alec, Ghosh Tusharkanti, Horisberger Alice, Howard Kaitlyn, Pulford John, Murzin Ekaterina, Hancock Brandon, Jonsson Anna HelenaORCID, Seifert Jennifer, Feser Marie L., Norris Jill M., Cao Ye, Apruzzese William, Louis Bridges S.ORCID, Bykerk Vivian, Goodman Susan, Donlin LauraORCID, Firestein Gary S., Perlman Harris, Bathon Joan M., Hughes Laura B., Tabechian Darren, Filer Andrew, Pitzalis Costantino, Anolik Jennifer H.ORCID, Moreland Larry, Guthridge Joel M.ORCID, James Judith A., Brenner Michael B.ORCID, Raychaudhuri SoumyaORCID, Sparks Jeffrey A.ORCID, Michael Holers V., Deane Kevin D., Lederer James A., Rao Deepak A.ORCID, Zhang FanORCID,
Abstract
AbstractRheumatoid arthritis (RA) is a systemic autoimmune disease with currently no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in ‘At-Risk’ populations prior to clinical disease onset is crucial to establishing effective prevention strategies. Here, we applied mass cytometry to deeply characterize the immunophenotypes in blood from At-Risk individuals identified through the presence of serum antibodies to citrullinated protein antigens (ACPA) and/or first-degree relative (FDR) status (n=52), as compared to established RA (n=67), and healthy controls (n=48). We identified significant cell expansions in At-Risk individuals compared with controls, including CCR2+CD4+ T cells, T peripheral helper (Tph) cells, type 1 T helper cells, and CXCR5+CD8+ T cells. We also found that CD15+ classical monocytes were specifically expanded in ACPA-negative FDRs, and an activated PAX5lownaïve B cell population was expanded in ACPA-positive FDRs. Further, we developed an “RA immunophenotype score” classification method based on the degree of enrichment of cell states relevant to established RA patients. This score significantly distinguished At-Risk individuals from controls. In all, we systematically identified activated lymphocyte phenotypes in At-Risk individuals, along with immunophenotypic differences among both ACPA+ and ACPA-FDR At-Risk subpopulations. Our classification model provides a promising approach for understanding RA pathogenesis with the goal to further improve prevention strategies and identify novel therapeutic targets.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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