Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis 
Rheumatoid arthritis (RA) is a systemic autoimmune disease with no universally effective prevention strategies. Identifying pathogenic immune phenotypes in ‘At-Risk’ populations prior to disease onset is crucial to establishing effective prevention strategies.
We deeply characterized the immunophenotypes in blood from At-Risk individuals (the presence of serum antibodies to citrullinated protein antigens (ACPA) and/or first-degree relative (FDR) status) as compared to established RA and healthy controls enrolled from the AMP RA/SLE Network.
This Github Repo includes the source code for the computational analyses involved in this work.
Overview of our analytical strategy: including 1) integrative clustering, 2) co-varying neighborhood analysis-based disease association, and 3) classification modeling.
We systematically identified activated lymphocyte phenotypes in At-Risk individuals, along with immunophenotypic differences between different At-Risk subpopulations.
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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.
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We also found that CD15+ classical monocytes were specifically expanded in ACPA-negative FDRs, and an activated PAX5low naïve B cell population was expanded in ACPA-positive FDRs.
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, providing a promising approach for understanding RA pathogenesis with the goal to develop effective prevention strategies.
Inamo J, Keegan, J., Griffith, A., Ghosh, T., Horisberger, A., Howard, K., Pulford, J., Murzin, E., Hancock, B., Jonsson, A.H., Seifert, J., Feser, M.L., Norris, J.M., Cao, Y., Apruzzese, W., Bridages, S.L., Bykerk, V., Goodman, S., Donlin, L., Firestein, G.S., Perlman, H., Bathon, J.M., Hughes, L.B., Tabechian, D., Filer, A., Pitzalis, C., Anolik, J.H., Moreland, L., Guthridge, J., James, J., Brenner, M.B., Raychaudhuri, S., Sparks, J.A., The AMP RA/SLE, …, Holers, V.M., Deane, K.D., Lederer, J.A., Rao, D.A., Zhang, F. Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis, bioRxiv, doi:10.1101/2023.07.03.547507, 2023
Please contact us (Jun Inamo: JUN.INAMO@CUANSCHUTZ.EDU) with any questions or comments.
The data presented here comes from the laboratory of Dr. Fan Zhang through collaborating with AMP RA/SLE Network.
