Role of circulating T follicular helper subsets and T follicular helper effector memory cells in systemic lupus erythematosus

Abstract

Objective: To investigate the role of T follicular helper (Tfh) subsets and T follicular helper effector memory (Tfhem) cells in circulation of patients with systemic lupus erythematosus (SLE), and explore their roles in SLE disease activity index as biomarkers. Methods: This study enrolled 64 patients with SLE and 15 healthy controls. In peripheral blood from patients with SLE and health controls, the percentage of Tfhem (CD3(+)CD4(+)CD45RA(-)CXCR5(+)CCR7(low)PD-1(high)) cells, Tfh (CD3(+)CD4(+)CD127(high)CD25(l)ow CD45RA(-)CXCR5(+)) subset: Tfh1 (CXCR3(+)CCR6(-)Tfh), Tfh2 (CXCR3(-)CCR6(+) Tfh), Tfh17 (CXCR3(-)CCR6(+) Tfh), were detected by flow cytometry. The correlations of Tfhem/Tfh subsets with clinical indicators which we collected were analyzed. Results: The percentage of Tfhem was significantly increased in SLE patients compare to health controls (1.40±1.12 vs 0.51±0.24, P<0.000 1), and it was also correlated with systemic lupus erythematosus disease activity index (SLEDAI) (P=0.015 3) and anti-dsDNA antibody (P=0.003 1), but not with complement C3 (C3), complement C4 (C4), erythrocyte sedimentation rate (ESR), and C reaction protein (CRP). In addition, the percentage of Tfh2, but not Tfh1 or Tfh17, was significantly increased in SLE patients compare to health controls (3.83±2.74 vs 2.18±1.07, P=0.000 4). As compared to anti-dsDNA antibody<25 group, the percentage of Tfh2 in anti-dsDNA antibody>25 group was increased with no significant statistical difference (4.33±3.20 vs 3.70±1.070, P=0.069 6). Conclusion: Our investigation show that Tfhem is associated with SLEDAI and it is a valuable evaluation biomarker for disease process and treatment. Meanwhile Tfhem is also associated with anti-dsDNA antibody, and it plays an important role in autoantibody production in SLE pathogenesis. Tfhem may be a good therapeutic target in SLE. For the meantime, the percentage of Tfh2 is significantly increased in SLE patients, and it had certain correlation with anti-dsDNA antibody, it might be involved in the development of SLE.