The Imbalance of Circulating Follicular T Helper Cell Subsets in Primary Sjögren’s Syndrome Associates With Serological Alterations and Abnormal B-Cell Distribution

Abstract

Since B-cell hyperactivity and pathologic antibody response are key features in the immunopathogenesis of primary Sjögren’s syndrome (pSS), the role of follicular T helper (TFH) cells as efficient helpers in the survival and differentiation of B cells has emerged. Our aim was to investigate whether a change in the balance of circulating (c)TFH subsets and follicular regulatory T (TFR) cells could affect the distribution of B cells in pSS. Peripheral blood of 38 pSS patients and 27 healthy controls was assessed for the frequencies of cTFH cell subsets, TFR cells, and certain B cell subpopulations by multicolor flow cytometry. Serological parameters, including anti-SSA, anti-SSB autoantibodies, immunoglobulin, and immune complex titers were determined as part of the routine diagnostic evaluation. Patients with pSS showed a significant increase in activated cTFH cell proportions, which was associated with serological results. Frequencies of cTFH subsets were unchanged in pSS patients compared to healthy controls. The percentages and number of cTFR cells exhibited a significant increase in autoantibody positive patients compared to patients with seronegative pSS. The proportions of transitional and naïve B cells were significantly increased, whereas subsets of memory B cells were significantly decreased and correlated with autoantibody production. Functional analysis revealed that the simultaneous blockade of cTFH and B cell interaction with anti-IL-21 and anti-CD40 antibodies decreased the production of IgM and IgG. Imbalance in TFH subsets and TFR cells indicates an ongoing over-activated humoral immune response, which contributes to the characteristic serological manifestations and the pathogenesis of pSS.

Multi-Omic Biomarkers for Patient Stratification in Sjogren’s Syndrome—A Review of the Literature

“…In 2021, Szabó et al [ 32 ] published an article whose aim was to investigate whether the distribution of B cells in pSS could be affected by a change in the balance of circulating T follicular helper (Tfh) cell subsets and follicular regulatory T cells. Utilising multicolour flow cytometry, they discovered that pSS patients had a significant increase in activated Tfh cells compared to HCs.…”

Alterations in B- and circulating T-follicular helper cell subsets in immune thrombotic thrombocytopenic purpura

“…[40][41][42] Similar reductions in the memory B cell compartments have been described in sarcoidosis, systemic sclerosis and Sjogren's syndrome. 40,[43][44][45][46][47][48] Comparing immunophenotype results between different studies is complex due to the variety of staining and gating protocols used, and clinical and demographic characteristics of the patient cohort, but some general conclusions can be made regarding iTTP in comparison to other autoimmune diseases. We found an increased ratio of naïve to switched memory B cells and higher plasmablasts in the acute patients.…”

Exploiting the role of T cells in the pathogenesis of Sjögren’s syndrome for therapeutic treatment

“…There are many subtypes of Tfh cells, such as Tfh1, Tfh2, and Tfh17-like cells, the latter are significantly increased in the peripheral blood of patients with SS ( 22 ). Additionally, some experiments showed that CXCR5 + PD-1 + Tfh cells in the blood of patients with SS were unchanged compared with those in individuals without SS, but the effects of Tfh1-like cells were more significant than those of Tfh2 and Tfh17-like cells ( 19 , 20 ). An increase in Tfh (CD4 + CXCR5 + ) cells was detected in the labial glands of patients with SS compared to that in normal controls.…”