Characterization of age‐associated B cells in early drug‐naïve rheumatoid arthritis patients. Issue 4 (10th November 2022)

• Record Type: Journal Article
• Authors: Vidal‐Pedrola, Gemma; Naamane, Najib; Cameron, James A.; Pratt, Arthur G.; Mellor, Andrew L.; Isaacs, John D.; Scheel‐Toellner, Dagmar; Anderson, Amy E.
• Is Part Of: Immunology. Volume 168:Issue 4(2023)
• Page Start: 640
• Page End: 653
• Publication Date: 2022-11-10
• Subjects: age‐associated B cells -- chemokine receptors -- FcRL family -- rheumatoid arthritis -- transcriptome; Immunology -- Periodicals
• DOI: 10.1111/imm.13598
• Languages: English
• ISSNs: 0019-2805

Abstract

Abstract: Age‐associated B cells (ABCs) are an immune cell subset linked to autoimmunity, infection and ageing, and whose pathophysiological importance was recently highlighted using single cell synovial tissue profiling. To elucidate their pathophysiological relevance, peripheral blood (PB) ABCs from early rheumatoid arthritis (eRA) patients naïve to disease‐modifying anti‐rheumatic drugs (DMARDs) were compared with their synovial fluid (SF) counterparts, and to PB ABCs from psoriatic arthritis patients and healthy controls. PB and SF B‐cell subsets were phenotyped by multi‐parameter flow cytometry, sorted and subjected to gene expression profiling (NanoString nCounter® Immunology V2 Panel) and functional characterization (stimulated cytokine measurements by immunoassay). PB ABCs of eRA patients, which are transcriptionally distinct from those of control cohorts, express chemokine receptors and adhesion molecules, such as CXCR3, that favour homing to inflammatory sites over lymphoid tissue. These cells are an activated, class‐switched B‐cell subset expressing high levels of HLA‐DR, co‐stimulatory molecules and T‐bet. Their secretion profile includes IL‐12p70 and IL‐23 but low levels of IL‐10. High surface expression of FcRL family members, including FcRL3, furthermore suggests a role for these cells in autoimmunity. Finally, and unlike in the periphery where they are rare, ABCs are the predominant B‐cell subsets in SF. These observations indicate the predilection of ABCs for inflammatory tissue in RA, where their propensity for antigen presentation and pro‐inflammatory phenotype may support autoimmune pathology. Their potential as a therapeutic target therefore warrants further study. Abstract : Age‐associated B cells have a distinct transcriptome compared to other B‐cell subsets. These cells express inflammatory‐homing chemokine receptors, as well as FcRL family members that are linked to autoimmune disease. Furthermore, B cells that resemble age‐associated B cells are enriched in rheumatoid arthritis synovial fluid. Age‐associated B cells are a potentially pathogenic cell in rheumatoid arthritis and are a novel therapeutic target that warrant further investigation.