Session Type: Abstract Submissions (ACR)
Background/Purpose: Autoreactive B cells in SLE undergo autoantigen selection, suggesting a requirement for germinal center follicular helper T (Tfh) cells in their maturation. However, evidence for dysregulation of Tfh cells in SLE and their potential contribution to disease remains unclear. Recently, blood CXCR5+ CD4 T cells, a heterogeneous pool consisting of functionally distinct Th1-, Th2-, and Th17-like subsets, have been proposed to be the circulating counterpart of Tfh (cTfh) cells. We now ask if changes in cTfh markers or subset composition within blood CXCR5+ cells are found in SLE patients, and the extent to which such alterations are associated with B cell and disease activity.
Methods: Blood samples from 49 clinically well-characterized SLE patients, 28 Behçet’s disease (BD) patients, and 16 healthy controls were included. Expression of Tfh surface markers (CXCR5; ICOS, inducible T-cell costimulator; PD-1, programmed cell death protein-1), composition of blood CXCR5+ subsets, and frequency of plasmablasts were enumerated by flow cytometry. The phenotype of blood CXCR5+ subsets was correlated with disease activity, clinical history, and plasmablast expansion.
Results: SLE patients had significant expansion of CXCR5+ICOS+PD-1+ CD4 T cells compared to controls (p < 0.001). PD-1, but not ICOS or CXCR5, expression was markedly elevated in CD4 T cells of SLE patients compared to BD patients and healthy controls (p < 0.001). PD-1 MFI in CXCR5+ cells correlated with SLE disease activity index (SLEDAI; Spearman r = 0.43, p = 0.03). PD-1 MFI also correlated with expansion of plasmablasts (Spearman r = 0.34, p = 0.02). In SLE patients with high anti-dsDNA antibody titers, PD-1 expression in CXCR5+ cells was also significantly elevated compared to patients with no detectable titers (p = 0.004). Enhanced PD-1 expression was neither a function of disease duration nor past activity; rather, it reflected current disease activity. Compared to BD patients, SLE patients also had an increase in the CXCR5+ Th2 (p < 0.05) and a decrease in the Th17 (p < 0.001) subsets. Concurrently, PD-1 expression in SLE patients was significantly higher in CXCR5+ Th2 cells compared to Th17 cells (p < 0.01). The expansion of the CXCR5+ Th2 subset was also positively associated with SLEDAI scores.
Conclusion: Our results demonstrate that dysregulation of cTfh cells is strongly correlated with disease activity in SLE, supporting a potential causal relationship. The altered composition of blood CXCR5+ cells also appeared to be a fundamental cellular defect in SLE, with our results revealing a novel dimension of Tfh dysregulation that may be central to disease pathogenesis.
H. E. Ho,
J. Y. Choi,
V. M. Bunin,
S. G. Pasoto,
E. F. Borba,
C. R. Goncalves,
P. R. Costa,
E. G. Kallas,
J. E. Craft,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/altered-circulating-follicular-helper-t-cell-phenotype-and-subset-composition-are-associated-with-disease-activity-in-patients-with-systemic-lupus-erythematosus/