Session Information
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.
Disclosure:
H. E. Ho,
None;
J. Y. Choi,
None;
V. M. Bunin,
None;
S. G. Pasoto,
None;
S. Carrasco,
None;
E. F. Borba,
None;
C. R. Goncalves,
None;
P. R. Costa,
None;
E. G. Kallas,
None;
E. Bonfa,
None;
J. E. Craft,
None.
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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/