PD-1+CXCR5−CD4+T cells are correlated with the severity of systemic lupus erythematosus

• Published in: Rheumatology (Oxford, England) England), 2019-12, Vol.58 (12), p.2188-2192
• Main Authors: Lin, Jin, Yu, Ye, Ma, Jilin, Ren, Chunyun, Chen, Weiqian
• Format: Article
• Language: English
• Subjects: Adolescent; ADP-ribosyl Cyclase 1 - metabolism; Adult; Arthritis - etiology; Arthritis - immunology; Blood Sedimentation; Case-Control Studies; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Exanthema - etiology; Exanthema - immunology; Female; Flow Cytometry; Histocompatibility Antigens Class II - metabolism; Humans; Inducible T-Cell Co-Stimulator Protein - metabolism; Interleukins - metabolism; Lupus Erythematosus, Systemic - complications; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Lupus Erythematosus, Systemic - physiopathology; Lupus Nephritis - etiology; Lupus Nephritis - immunology; Male; Middle Aged; Pericarditis - etiology; Pericarditis - immunology; Pleurisy - etiology; Pleurisy - immunology; Programmed Cell Death 1 Receptor - metabolism; Receptors, CCR6 - metabolism; Receptors, CXCR3 - metabolism; Receptors, CXCR5 - metabolism; Severity of Illness Index; T-Lymphocyte Subsets; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Young Adult
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kez228

Abstract Objectives PD-1+CXCR5−CD4+T peripheral helper (Tph) cells, a recently identified T cell subset, are proven to promote B cell responses and antibody production in rheumatoid arthritis, but their role in the pathogenesis of SLE is unknown. We explored the role of Tph in lupus disease development. Methods This cohort study included 68 patients with SLE and 41 age- and sex-matched healthy individuals. The frequency of PD-1+CXCR5−CD4+T cells was analysed in peripheral blood by flow cytometry. Inducible T-cell costimulator, CD38, MHC-II, IL-21, CXCR3 and CCR6 expression were measured in Tph cells. Comparisons between the two groups were performed, and correlations between Tph cells and other parameters were investigated. Results We revealed a markedly expanded population of Tph cells (8.31 ± 5.45 vs 2.86 ± 1.31%, P < 0.0001) in the circulation of patients with SLE (n = 68), compared with healthy controls (n = 41). Tph cells were much higher in the active group than in the inactive group (14.21 ± 5.21 vs 5.49 ± 2.52%, P < 0.0001). Tph cells were significantly associated with SLEDAI score (r = 0.802), ESR (r = 0.415), IgG (r = 0.434), C3 (r = −0.543), C4 (r = −0.518) and IL-21 level (r = 0.628), and ANA titre (r = 0.272). Furthermore, Tph cells were much higher in lupus patients with arthritis, nephritis, rash, alopecia, pleuritis, pericarditis and haematological involvement. Tph cells were associated with CD138+/CD19+ plasma cells (r = 0.518). Furthermore, MHC-II, inducible T-cell costimulator, CD38, and IL-21 expression were all higher in Tph cells from SLE patients compared with healthy controls. CXCR3+CCR6−Tph (Tph1) cells were expanded in the SLE patients. Conclusion Our data show that relative number of Tph cells is correlated with disease measures in patients with SLE, suggesting an important role in lupus disease development.