Objectives: Sjögren's syndrome (SjS) patients exhibit great phenotypical heterogeneity, reinforced by the positiveness of anti-SSA antibody. We aimed to evaluate lymphocyte subpopulations in SSA-positive (SSA+SjS) and SSA-negative (SSA-SjS) SjS patients, Sicca patients, and healthy controls (HC), and to investigate associations between lymphocyte subpopulations and disease activity in SjS.
Methods: According to the fulfilment of the ACR/EULAR 2016 classification criteria, patients were included as SjS or as Sicca. HC were selected from the Ophthalmology outpatient clinic. Lymphocyte subpopulations were characterized by flow cytometry. Statistical analysis was performed with GraphPad Prism, with statistical significance concluded if p < 0.05.
Results: We included 53 SjS patients (38 SSA+ and 15 SSA-), 72 Sicca, and 24 HC. SSA+SjS patients presented increased IL-21CD4 and CD8 T cells compared to Sicca and HC, whereas compared to SSA-SjS patients, only IL-21CD4 T cell percentages were increased and Tfh17 percentages and numbers were decreased. Compared to Sicca and HC, SSA+SjS patients had higher levels of CD24CD38 B cells, naïve B cells, and IgMCD38 plasmablasts, and lower levels of memory B cells, including CD24CD27 B cells. SSA+SjS patients with clinically active disease had positive correlations between ESSDAI and IL-21CD4 (p = 0.038, r = 0.456) and IL-21CD8 T cells (p = 0.046, r = 0.451).
Conclusions: In SjS, a distinct lymphocyte subset distribution profile seems to be associated with positive anti-SSA. Moreover, the association between ESSDAI and IL-21CD4 and IL-21CD8 (follicular) T cells in SSA+SjS patients suggests the involvement of these cells in disease pathogenesis and activity, and possibly their utility for the prognosis and assessment of response to therapy. Key Points • SSA+SjS patients have a pronounced naïve/memory B cell imbalance. • SSA+SjS patients have more active disease associated with IL-21CD4 and IL-21CD8 follicular T cell expansion. • IL-21CD4 and IL-21CD8 T cell quantification may be useful for the prognosis and assessment of response to therapy.
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