Back to Search Start Over

Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis.

Authors :
Inamo J
Keegan J
Griffith A
Ghosh T
Horisberger A
Howard K
Pulford J
Murzin E
Hancock B
Jonsson AH
Seifert J
Feser ML
Norris JM
Cao Y
Apruzzese W
Louis Bridges S
Bykerk V
Goodman S
Donlin L
Firestein GS
Perlman H
Bathon JM
Hughes LB
Tabechian D
Filer A
Pitzalis C
Anolik JH
Moreland L
Guthridge JM
James JA
Brenner MB
Raychaudhuri S
Sparks JA
Michael Holers V
Deane KD
Lederer JA
Rao DA
Zhang F
Source :
BioRxiv : the preprint server for biology [bioRxiv] 2023 Jul 04. Date of Electronic Publication: 2023 Jul 04.
Publication Year :
2023

Abstract

Rheumatoid 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 PAX5 <superscript>low</superscript> naïve 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.

Details

Language :
English
ISSN :
2692-8205
Database :
MEDLINE
Journal :
BioRxiv : the preprint server for biology
Publication Type :
Academic Journal
Accession number :
37461737
Full Text :
https://doi.org/10.1101/2023.07.03.547507