T follicular-like helper cells in the peripheral blood of patients with primary Sjögren's syndrome

K A Brokstad; M Fredriksen; F Zhou; B Bergum; J G Brun; R J Cox; K Skarstein

doi:10.1111/sji.12679

T follicular-like helper cells in the peripheral blood of patients with primary Sjögren's syndrome

Scand J Immunol. 2018 Aug;88(2):e12679. doi: 10.1111/sji.12679.

Authors

K A Brokstad¹, M Fredriksen¹, F Zhou², B Bergum¹, J G Brun³, R J Cox^{2

4

5}, K Skarstein⁶

Affiliations

¹ Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.
² The Influenza Center, Department of Clinical Science, University of Bergen, Bergen, Norway.
³ Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.
⁴ Jebsen Centre for Influenza Vaccine Research, University of Bergen, Bergen, Norway.
⁵ Department of Research and Development, Haukeland University Hospital, Bergen, Norway.
⁶ Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.

PMID: 29882349
DOI: 10.1111/sji.12679

Abstract

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by exocrine gland dysfunction, mainly causing sicca symptoms. B cells have a prominent role in SS, and the T follicular helper (T_FH ) cells provide B cells with survival and specialization signals in germinal centres. Here, we investigate peripheral T_FH cells in pSS. Sixteen pSS patients and healthy controls were enrolled in the study, with 13 women and 3 men in each group. Whole blood was collected and separated into PBMC and plasma, followed by cryopreservation. Plasma samples were analysed for Ro52, Ro60 and La48 autoantibodies by indirect ELISA. For flow cytometric analysis, we defined 4 subsets of TFH-like cells within the CD3⁺ CD4⁺ CXCR5⁺ population, namely the ICOS^- PD-1^- , ICOS^- PD-1⁺ , ICOS⁺ PD-1^- and ICOS⁺ PD-1⁺ ("TFH") cells. We also investigated 4 CD19⁺ B cell subsets, the CD20⁺ CD27⁺ CD38^- memory B cells, CD20⁺ CD27⁺ CD38⁺ memory B cells, CD20^- CD27⁺ CD38⁺⁺ CD138^- plasmablasts and CD20^- CD27⁺ CD38⁺⁺ CD138⁺ plasma cells. We observed higher fractions of ICOS⁺ PD-1^- cells, ICOS⁺ PD-1⁺ ("T_FH ") cells and plasmablasts in pSS patients compared to controls, and lower frequencies of both types of memory B cells. The number of T_FH cells correlated positively with the levels of plasmablasts and plasma cells in the pSS patients, but not in the controls. The pSS patients were stratified according to Ro52/Ro60/La48 serology, and a positive association was found between autoantibody levels and increased level of T_FH cells, plasmablasts and plasma cells and lowered levels of memory B cells. We observed a higher response to Ro/La stimulation in pSS patients compared to controls of the memory B cells, although only significantly for the CD38^- memory B cells. Overall, a pathological relation between the ICOS⁺ T follicular-like helper cells and B cells in pSS was observed, but further work should be conducted to explore their overall impact upon disease progression.

Keywords: B cells; Sjögren's syndrome; T follicular helper cells.