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.
Inamo J, Keegan, J., Griffith, et al. 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. The data is available through the ARK Portal under the DOI https://doi.org/10.7303/syn64425850.2 and here.
The results published here are in whole or in part based on data obtained from the ARK Portal. The Accelerating Medicines Partnership® RA/SLE Network data used for this publication are available under the DOI https://doi.org/10.7303/syn64425850.2. The ARK Portal hosts data generated by a network of research teams working collaboratively to deepen the understanding of Arthritis and Autoimmune and Related Diseases. It was established by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and includes data from the Accelerating Medicines Partnership® (AMP®) RA/SLE program. The specific data used in this publication is available as a controlled-access dataset. Researchers seeking to use these data must submit:
- A detailed intended data use statement
- A completed and signed data use certificate These access requirements ensure responsible and ethical data sharing within the research community. Instructions for access are available at https://help.arkportal.org/help/data-use-certificate#DataUse&Acknowledgement-Acknowledgement.
