Background CD4⁺ T cells are central mediators in specific autoimmune diseases; however, it remains challenging to define their key effector functions in systemic erythematosus lupus (SLE), a chronic immune-mediated damage to the whole system. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands. PD-1⁺CD4⁺T cells could be divided into PD-1⁺CXCR5^-CD4⁺T peripheral helper cells and PD-1⁺CXCR5⁺CD4⁺ T (Tfh) cells according to CXCR5 expression. PD-1⁺CXCR5^-CD4⁺T peripheral helper (Tph) cells were proven to promote B cell responses and antibody production in rheumatoid arthritis Rao DA, Nature, 2017.¹ Tfh cells were required for the generation of most memory B cells and long-lived plasma cells in SLE. However, what the role of Tph cells in the pathogenesis of SLE was unknown.

Objectives We assessed that whether Tph cells were associated with clinical profiles of patients with SLE.

Methods This cohort study included 36 patients with SLE from the Division of Rheumatology, the first Affiliated Hospital, college of medicine, Zhejiang University. All SLE patients fulfilled the American College of Rheumatology revised classification criteria. 26 Age- and sex-matched healthy individuals had no connective tissue disorders, neoplasms or current infections. Here we used flow cytometry to analyse PD-1⁺CXCR5^-CD4⁺T cells in peripheral blood from patients with SLE. Correlation between Tph cells and other parameters was investigated by Spearman’s correlation coefficient test, and comparisons between groups were performed using nonparametric Mann-Whitney test.

Results Firstly, we revealed a markedly expanded population of Tph cells (8.95±6.35 vs. 2.67±1.22, p<0.0001) in the circulation of patients with SLE (n=36), compared to healthy controls (n=26) (figure1a, b). And Tph cells were much higher in active group than those in inactive group (13.21±5.96 vs. 4.19±1.59, p<0.0001) (figure 1a, c). Secondly, like Tfh cells (r=0.611, p<0.0001), Tph cells (r=0.829, p<0.0001) were significantly associated with SLEDAI scores (figure 1d). Tph cells were associated with IgG (r=0.650, p<0.001) (figure 1e), C3(r=−0.528, p=0.001) (figure 1 f), C4 levels (r=−0.561, p=0.001) (figure 1 g), but not ESR, CRP, IL-2, IL-6, TNF-α, IFN-γ, and IL-17A levels. Furthermore, Tph cells were much higher in lupus patients with arthritis (17.71±10.05 vs. 11.14±6.84, p=0.045), in skin mucous group (18.71±6.08 vs. 10.32±7.32, p=0.004), in pleuritis (20.60±8.87 vs. 11.40±7. 24, p=0.025), in pericarditis group (26.65±0.21 vs. 11.58±7. 25, p=0.006), in group with haematological involvement (15.51±7.76 vs. 8.97±6.58, p=0.010), when compared to patients without relevant symptoms.

Conclusions Our data suggest that increased Tph cell proportions seem to have an important role in lupus disease development.

Reference [1] Rao DA, Gurish MF, Marshall JL, Slowikowski K, Fonseka CY, Liu Y, et al. Pathologically expanded peripheral t helper cell subset drives b cells in rheumatoid arthritis. Nature2017;542:110–4.

Acknowledgements This work is supported in part by grants from the National Natural Science Foundation of China (81701600), and Zhejiang Provincial Natural Science Foundation of China (LQ17H100001, LGF18H100001).

Disclosure of Interest None declared