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Abstract Number: 147

T Follicular Helper Cell Phenotype in RA Patients Receiving Rituximab

Betty Hsiao1, Jin-Young Choi2 and Joseph E. Craft3, 1Yale University School of Medicine, New Haven, CT, 2Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 3Department of Internal Medicine/Rheumatology, Yale University School of Medicine, New Haven, CT

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: rheumatoid arthritis (RA) and rituximab, T cells

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Session Information

Date: Sunday, October 21, 2018

Session Title: T Cell Biology and Targets in Autoimmune and Inflammatory Disease Poster

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: B and T cells contribute to tissue injury in rheumatoid arthritis (RA). Rituximab (RTX), an anti-CD20 monoclonal antibody, is used for the treatment of RA and results in rapid B-cell depletion. However, the therapeutic effect of RTX may not be entirely contingent on depletion of B cells; rather, we hypothesized a contributing factor is the dampening of their interplay with the T-cell drivers of their maturation in secondary lymphoid organs. The latter follicular helper T (Tfh) cells are represented in the blood as a circulating (cTfh) pool. Thus, we examined effects of RTX on cTfh cells in RA patients treated either for the first time (“naïve”) or on maintenance therapy (i.e.; received at least once prior; “maintenance”).

Methods: Blood was drawn from 5 naïve and 11 maintenance patients prior to the first infusion, at 2 weeks (prior to 2nd infusion, if given) and 12 weeks. Peripheral blood mononuclear cells were stained with antibodies conjugated with fluorochromes for flow cytometry—CD4, CD3, CD45RA, CXCR5, PD-1, ICOS, CCR7, CD127, CD25, TCRβ, CD19, IgD, CD38, CD27, PSGL-1, CD138, and CD5—to determine naïve, activated, and memory CD4 T cells, cTfh and cTfh subsets (cTfh1, cTfh2, cTfh17) and conventional CD4 T helper cell subsets (Th1, Th2, Th17). Naïve and memory B cells, and plasma cells were also enumerated. Data were analyzed using FlowJo® software. Plasma was assessed for anti-citrullinated peptide antibody (IgG) titers (ACPA) using QuantaLite® ELISA kit. Disease activity (DA) was determined by chart review.

Results: Naïve compared to maintenance patients had more cTfh cells (CXCR5+PD-1hiICOShi; 5.65 ± 0.68% vs. 2.67 ± 0.36%; among CD4 T cells), with a significant linear relationship between the percentage of cTfh and that of CD19+ B cells (Pearson’s correlation coefficient 0.52); more cTfh17 cells (CXCR3–CCR6+; 29.5 ± 2.79% vs. 21.42 ± 1.16%; within the CD4+CD45RA–CXCR5+ population); and more PD-1lo memory cTfh17 cells (35.42 ± 3.32% vs. 21.88 ± 1.27%), although their percentages and ACPA titers did not change over the course of therapy. Th17 cells were differentiated from cTfh17 cells by their expression of CXCR5– rather than CXCR5+. Naïve compared to maintenance patients also had more Th17 cells (CD4+CXCR5–CXCR3–CCR6+; 19.35 ± 1.54% vs. 14.27 ± 1.08%), in both the PD-1hi effector (16.38 ± 1.82% vs. 11.89 ± 0.87%) and PD-1lo memory subsets (20.77 ± 1.72% vs. 13.91 ± 1.07%). All naïve patients had moderate-to-high DA at baseline as compared to only 27% of maintenance patients; post-RTX, all naïve patients had either low DA or clinical remission as compared to 82% of the maintenance patients.

Conclusion: We found a higher percentage of cTfh cells in naïve compared to maintenance RA patients treated with RTX, consistent with prior studies showing that B-cell help is needed for Tfh-cell development. We also found a higher frequency of cTfh17 and Th17 cells in naïve compared to maintenance patients and correspondingly higher DA at baseline in naïve patients, suggesting that B-cell depletion results in reduced cTfh and Th17 cells, as DA improves. Future studies are needed to better understand these cTfh subsets and their correlation to B-cell depletion and DA in RA, as well as their potential as therapeutic targets.


Disclosure: B. Hsiao, None; J. Y. Choi, None; J. E. Craft, None.

To cite this abstract in AMA style:

Hsiao B, Choi JY, Craft JE. T Follicular Helper Cell Phenotype in RA Patients Receiving Rituximab [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/t-follicular-helper-cell-phenotype-in-ra-patients-receiving-rituximab/. Accessed April 1, 2023.
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