Background/Purpose: Increasing evidence points to immunological heterogeneity in the pathogenesis of SLE. Indeed, targeted therapy for SLE showed considerable variability of efficacy. Thus, it seems to be important to explore the characteristic and interaction among the immune cell phenotypes in this disease. The aim of this study was to assess the comprehensive peripheral immunophenotyping in a correlation with clinical manifestations in patients with SLE.

Methods: Peripheral blood mononuclear cells were obtained from 143 SLE patients and 49 healthy controls (HC) and the phenotype of circulating B, T, NK and dendritic cells was defined based on flow cytometric analysis for human immune system termed “the Human Immunology Project”. The correlation of immune cell phenotypes with clinical characteristics and responsiveness to immunosuppressive therapies, such as cyclophosphamide, mycophenolate mofetil, or calcineurin, in addition to high-dose glucocorticoids, were evaluated.

Results: The frequency of CD3⁺CD4⁺CXCR5⁺ICOS⁺CD69⁺ activated T follicular helper (Tfh) cell, but not CD3⁺CD4⁺CXCR3⁺CCR6^– Th1 cell and CD3⁺CD4⁺CXCR3^–CCR6⁺ Th17 cell, were higher in SLE than that in HC (mean 0.4 vs 0.2, p=0.03). The frequency of CD19⁺ CD20⁺IgD^–CD27⁺ class-switched memory B cell and CD19⁺CD20⁺IgD^–CD27^– double negative B cell were higher in SLE than that in HC (mean 23.6 vs 13.2 and 10.7 vs 5.5, p=0.03 and p=0.04, respectively). The largest difference relative to the HC was observed in the proportion of CD19⁺CD20^–CD27⁺CD38⁺ plasmablast, which was higher in SLE (mean 16.2 vs 3.3, p=001) and correlated with BILAG index (r=0.24, p<0.001). The proportion of activated Tfh cell significantly correlated with serum IgG level (r=0.20, p=0.02) and with serum anti-Sm antibody level (r=0.26, p=0.01). Among helper T cell subsets (Th1, Th17, Treg and Tfh), the proportion of Tfh cell or activated Tfh cell showed positive correlation with that of plasmablast (r=0.21, p=0.02). Treatment resulted in significant decreased proportions of plasmablast and Tfh cell (plasmablast; mean 17.6 to 10.1, p<0.01, Tfh; mean 1.1 to 0.7, p<0.01). The percentage of patients who showed treatment resistance was highest among patients with high percentage of Tfh cell (p=0.03).

Conclusion: Peripheral immunophenotyping indicated the pathological relevance of Tfh cell and plasmablast in patients with SLE, i.e. activation of Tfh cell correlated with autoantibody production while plasmablast did with disease activity of SLE. The peripheral immunophenotyping might be useful in evaluating the pathogenesis and in determining the therapeutic target of each patient.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pathological-relevance-of-t-follicular-helper-cell-and-plasmablast-in-patients-with-systemic-lupus-erythematosus/