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Abstract Number: 2277

Immunophenotyping of peripheral blood mononuclear cells reveals potential cellular biomarkers of disease in rheumatoid arthritis

John Bui1, Jason Dubovsky2, Jennifer Abrams3, Sara Charmsaz4, Michelle Blake1, Joshua Beilke4, Anne-Renee van der Vuurst de Vries1, Joseph Arron5, Jonathan Graf6 and Jeffrey Bluestone7, 1Sonoma Biotherapeutics, Seattle, WA, 2Sonoma Biotherapeutics, South San Francisco, 3Sonomabio, San Francisco, CA, 4Sonoma Biotherapeutics, Seattle, 5Sonoma Biotherapeutics, San Francisco, CA, 6UCSF, San Francisco, CA, 7Sonoma Biotherapeutics, South San Francisco, CA

Meeting: ACR Convergence 2025

Keywords: , , , ,

Session Information

Date: Tuesday, October 28, 2025

Title: (2265ā€“2289) Rheumatoid Arthritis ā€“ Treatment Poster III

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: Emerging cell-based therapies for rheumatoid arthritis (RA) target the underlying immunologic activity of disease. Objective biomarkers to-date are downstream sequelae of RA immunologic drivers. In this study, we sought to identify direct cellular biomarkers in RA by comprehensively profiling immune subsets from whole blood.

Methods: Here, three flow cytometry panels measuring 18 markers were used to identify T cell subsets. PBMC were profiled from 30 RA subjects with varying disease severity measured by DAS28-CRP, DAS28-ESR and CDAI in addition to 23 age-, gender-, and race-matched healthy donor control subjects (HD). A two-tiered approach was applied for data analysis: Tier 1) Identify cell subsets significantly different between RA and HD and Tier 2) Correlate cell subsets identified in Tier 1 with RA clinical disease severity.

Results: The analysis revealed a significant difference (pā‰¤0.001) between RA (12%) and HD (39%) in the frequency of an effector regulatory T cells (Treg) phenotype defined by CD4+FOXP3+CD25hiCD45RA-. Furthermore, the frequency of these cells was inversely correlated with disease severity measured by DAS28-CRP (r = -0.525, p = 0.039). Activation and proliferation markers on the Tregs in the RA subjects were similarly inversely correlated with DAS28-CRP (r= -0.53 HLA-DR, r= -0.49 CTLA-4, r= -0.52 Ki67). In contrast, the T effector cell subset phenotype data reveal significantly higher frequency (p=0.001) of CD4+CD45RA-CCR7+ central memory CD4+ T cells (Tcm) in RA (31%) compared to HD (20%). Moreover, the frequency of CD4+ Tcm was positively correlated with DAS28-ESR (r = 0.615, p = 0.037).

Conclusion: We show that, compared to healthy subjects, RA patients have significantly reduced proportion of Tregs with an effector phenotype and a higher proportion of CD4 Tcm. These phenotypic frequencies correlate with disease severity, highlighting a relationship of these immune subsets to the pathogenesis of RA. Additional characterization of these subsets will be pursued to determine their potential utility as pharmacodynamic biomarkers.

Disclosures: J. Bui: Sonoma Biotherapeutics, 3; J. Dubovsky: Sonoma Biotherapeutics, 3; J. Abrams: None; S. Charmsaz: None; M. Blake: Sonoma Biotherapeutics, 3, 11; J. Beilke: Sonoma Biotherapeutics, 3; A. van der Vuurst de Vries: None; J. Arron: Sonoma Biotherapeutics, 12,, 3, 4; J. Graf: None; J. Bluestone: Gilead, 4.

To cite this abstract in AMA style:

Bui J, Dubovsky J, Abrams J, Charmsaz S, Blake M, Beilke J, van der Vuurst de Vries A, Arron J, Graf J, Bluestone J. Immunophenotyping of peripheral blood mononuclear cells reveals potential cellular biomarkers of disease in rheumatoid arthritis [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/immunophenotyping-of-peripheral-blood-mononuclear-cells-reveals-potential-cellular-biomarkers-of-disease-in-rheumatoid-arthritis/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunophenotyping-of-peripheral-blood-mononuclear-cells-reveals-potential-cellular-biomarkers-of-disease-in-rheumatoid-arthritis/