Abstract
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 PrismTM, 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-21+CD4+ and CD8+ T cells compared to Sicca and HC, whereas compared to SSA−SjS patients, only IL-21+CD4+ T cell percentages were increased and Tfh17 percentages and numbers were decreased. Compared to Sicca and HC, SSA+SjS patients had higher levels of CD24HiCD38Hi B cells, naïve B cells, and IgM-/+CD38++ plasmablasts, and lower levels of memory B cells, including CD24HiCD27+ B cells. SSA+SjS patients with clinically active disease had positive correlations between ESSDAI and IL-21+CD4+ (p = 0.038, r = 0.456) and IL-21+CD8+ 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-21+CD4+ and IL-21+CD8+ (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-21+CD4+ and IL-21+CD8+ follicular T cell expansion. • IL-21+CD4+ and IL-21+CD8+ T cell quantification may be useful for the prognosis and assessment of response to therapy. |
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Acknowledgments
The first author gratefully acknowledges Academia Cuf/José de Mello Saúde and Sociedade Portuguesa de Reumatologia for its financial support. The authors gratefully acknowledge the laboratory staff that assisted in the flow cytometry analysis.
Funding
The project was partially financed by Academia Cuf/José de Mello Saúde, Carnaxide, Portugal, and Sociedade Portuguesa de Reumatologia, Lisbon, Portugal.
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F Barcelos and C Martins conceived the original research idea, while all of the authors designed the study and created the study protocol. F Barcelos, J Vaz-Patto, and N Madeira recruited the patients and collected the data. J Cardigos and N Alves recruited the healthy controls and collected the data. C Martins analyzed the blood samples using flow cytometry. C Martins and M Ângelo-Dias performed the statistical analysis. JC Branco and L-M Borrego supervised all the work and the research protocol. All of the authors contributed to data analysis and interpretation. F Barcelos and N Madeira drafted the manuscript, and all of the authors revised it and contributed to it intellectually. All of the authors have approved the final version of the manuscript.
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This study was approved by the Ethics committee of Hospital CUF Descobertas, 8/09/2014, Ethics committee of Instituto Português de Reumatologia, 3/07/2015 and NOVA Medical School Ethics (no 17/2016/CEFCM).
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ESM 1
SjS, Sjögren’s syndrome; HC, Healthy Controls; IQR, Interquartile range. Mann-Whitney nonparametric U test was used for group’s comparison. Results are presented as medians and interquartile range, median (IQR). Statistically significant results are indicated in bold. (DOCX 23 kb)
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Barcelos, F., Martins, C., Madeira, N. et al. Lymphocyte subpopulations in Sjögren’s syndrome are distinct in anti-SSA-positive patients and related to disease activity. Clin Rheumatol 40, 2791–2804 (2021). https://doi.org/10.1007/s10067-020-05537-y
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DOI: https://doi.org/10.1007/s10067-020-05537-y