目的:研究原发性干燥综合征 (pSS) 患者外周血中Breg、Tfh及Tfr细胞表达变化及意义。方法:选取2022年3月至2022年7月于包头医学院第一附属医院新诊断为pSS且符合筛选标准的患者20例作为试验组,分别于治疗前与治疗3～6月后收取外周血。同时收取年龄、性别匹配的健康人外周血20例作为对照组。分别收集试验组患者治疗前后疾病活动度ESSDAI、ESSPRI评分、血沉(ESR)、C-反应蛋白(CRP),免疫球蛋白G(IgG)等相关化验结果。采取流式细胞计数的方法观察CD19+CD24highCD27+Breg、CD4+CXCR5+Tfh及CD4+CXCR5+FoxP3+Tfr细胞表达。使用SPSS26进行数据分析。结果:试验组外周血Breg细胞、Tfh细胞较对照组低(P＜0.05);试验组外周血中Tfr与对照组差异无统计学意义(P＞0.05);试验组外周血中Tfr/Tfh比值较对照组高(P＜0.05);治疗后外周血Breg细胞数量较治疗前增加(P＜0.05);治疗后外周血Tfh、Tfr细胞数量较治疗前降低(P＜0.05);治疗后外周血中Tfr/Tfh比值与治疗前无显著差异。结论:外周血Breg、Tfh可能是提示pSS疾病进展的有效指标,为临床监测疾病进展、分期治疗提供新的思路。而Tfr、Tfr/Tfh 参与pSS的发病的机制可能需要更进一步的研究去证实。
Objective: To study the expression and significance of Breg, Tfh and Tfr cells in peripheral blood of patients with primary Sjögren's syndrome (pSS).Methods: From March 2022 to July 2022, 20 patients who were newly diagnosed with pSS and met the screening criteria in the First Affiliated Hospital of Baotou Medical College were selected as the experimental group. Peripheral blood was collected before treatment and 3 to 6 months after treatment. At the same time, 20 age-and sex-matched healthy human peripheral blood samples were collected as the control group. The disease activity ESSDAI, ESSPRI score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), immunoglobulin G (IgG) and other related test results were collected before and after treatment in the experimental group. In this study, the expression of CD19+CD24highCD27+Breg, CD4+CXCR5+Tfh及CD4+CXCR5+FoxP3+Tfr cells was observed by flow cytometry. SPSS26 was used for data analysis. Results: Breg cells and Tfh cells of the experimental group were lower than those of healthy control group (P＜0.05); There was no significant difference between the Tfr in the experimental group and the healthy control group (P＞0.05);The ratio of Tfr/Tfh in the experimental group was higher than that of healthy control group (P＜0.05);Compared with before treatment, the number of Breg cells in peripheral blood after treatment was increased (P＜0.05); Compared with before treatment, the number of Tfh and Tfr cells in peripheral blood after treatment was decreased (P＜0.05);There was no significant difference in the Tfr/Tfh ratio in peripheral blood between after treatment and before treatment (P＞0.05). Conclusion: Breg and Tfh in peripheral blood may be effective indicators to indicate the progress of pSS disease, providing a new idea for clinical monitoring of disease progress and stage treatment. The mechanism of Tfr and Tfr/Tfh participating in the pathogenesis of pSS may need further research to confirm.
[1] Negrini S, Emmi G, Greco M, et al. Sjögren's syndrome: asystemic autoimmune disease[J].Clin Exp Med, 2022,22(1): 9-25.
[2] Psianou K, Panagoulias I, Papanastasiou AD, et al. Clinical and immunological parameters of Sjögren's syndrome[J].Autoimmunity Reviews, 2018,17(10): 1053-1064.
[3] Bombardieri M, Argyropoulou OD, Ferro F, et al. One year in review 2020: pathogenesis of primary Sjögren's syndrome[J].Clin Exp Rheumatol, 2020,38 Suppl 126(4): 3-9.
[4] Du W, Han M, Zhu X, et al. The multiple roles of B cells in the pathogenesis of sjögren's syndrome[J].Front Immunol, 2021,12: 684999.
[5] Jansen K, Cevhertas L, Ma S, et al. Regulatory B cells, A to Z[J].Allergy, 2021,76(9): 2699-2715.
[6] Wei X, Niu X. T follicular helper cells in autoimmune diseases[J].Journal of Autoimmunity, 2023,134: 102976.
[7] Fonseca V R, Ribeiro F, Graca L. T follicular regulatory (Tfr) cells: Dissecting the complexity of Tfr-cell compartments[J].Immunol Rev, 2019,288(1): 112-127.
[8] Ramos-Casals M, Brito-Zerón P, Bombardieri S, et al. EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies[J].Annals of the Rheumatic Diseases, 2020,79(1): 3-18.
[9] Guo J, Gu M, Zhang W, et al. Aberrant IL-35 levels in patients with primary Sjogren's syndrome[J].Scandinavian Journal of Immunolog, 2018,88(5): e12718.
[10] Iwata Y, Matsushita T, Horikawa M, et al. Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells[J].Blood, 2011,117(2): 530-541.
[11] Mavropoulos A, Varna A, Zafiriou E, et al. IL-10 producing Bregs are impaired in psoriatic arthritis and psoriasis and inversely correlate with IL-17- and IFNγ-producing T cells[J].Clinical Immunology (Orlando, Fla.), 2017,184: 33-41.
[12] 马卓娅,郑跃杰,王国兵,等. 调节性B细胞在接受脱敏治疗过敏性哮喘患儿中的变化及意义[J] .中华临床免疫和变态反应杂志,2021,15(4):376-383.
[13] Crotty S. T follicular helper cell biology: adecade of discovery and diseases[J].Immunity, 2019,50(5): 1132-1148.
[14] Wang Y, Guo H, Liang Z, et al. Sirolimus therapy restores the PD-1+ICOS+Tfh: CD45RA-Foxp3highactivated Tfr cell balance in primary Sjögren's syndrome[J].Molecular Immunology, 2022,147: 90-100.
[15] Jin L, Yu D, Li X, et al. CD4+CXCR5+ follicular helper T cells in salivary gland promote B cells maturation in patients with primary Sjögren's syndrome[J].Int J Clin Exp Pathol, 2014,7(5): 1988-1996.
[16] Szabó K, Papp G, Szántó A, et al. A comprehensive investigation on the distribution of circulating follicular T helper cells and B cell subsets in primary Sjögren's syndrome and systemic lupus erythematosus[J].Clinical and Experimental Immunology, 2016,183(1): 76-89.
[17] Chen W, Yang F, Xu G, et al. Follicular helper T cells and follicular regulatory T cells in the immunopathology of primary Sjögren's syndrome[J].Journal of Leukocyte Biology, 2021,109(2): 437-447.
[18] Costantino AB, Acosta CDV, Onetti L, et al. Follicular helper T cells in peripheral blood of patients with rheumatoid arthritis[J].Reumatol Clin, 2017,13(6): 338-343.
[19] Kim JW, Lee J, Hong SM, et al. Circulating CCR7loPD-1hifollicular helper T cells indicate disease activity and glandular inflammation in patients with primary sjögren'ssyndrome[J].Immune Netw, 2019,19(4): e26.
[20] Shulman Z, Gitlin AD, Targ S, et al. T follicular helper cell dynamics in germinal centers[J].Science, 2013,341(6146):673-677.
[21] Nguyen QP, Deng TZ, Witherden DA, et al. Origins of CD4+ circulating and tissue-resident memory T-cells[J].Immunology, 2019,157(1): 3-12.
[22] Walker LSK. The link between circulating follicular helper T cells and autoimmunity[J].Nat Rev Immunol, 2022,22(9): 567-575.
[23] Schroeder AR, Zhu F, Hu H. Stepwise Tfh cell differentiation revisited: new advances and long-standing questions[J].Faculty Reviews, 2021,10: 3.
[24] Fonseca VR, Agua-Doce A, Maceiras AR, et al. Human blood Tfr cells are indicators of ongoing humoral activity not fully licensed with suppressive function[J].Sci Immunol, 2017,2(14): eaan1487.
[25] Fonseca VR, Romão VC, Agua-Doce A, et al. The ratio of blood T follicular regulatory cells to T follicular helper cells marks ectopic lymphoid structure formation while activated follicular helper T cells indicate disease activity in primary sjögren'ssyndrome[J].Arthritis & Rheumatology (Hoboken, N.J.), 2018,70(5): 774-784.
