The subset composition of follicular T helpers and B lymphocytes in patients with ankylosing spondylitis depending on HLA-B27 status

P. Shesternya, A. A. Savchenko, I. V. Kudryavtsev, A. A. Masterova, A. Borisov
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Abstract

Immune relationships involved in a wide range of immunopathological conditions, including ankylosing spondylitis (AS), are formed due to the characteristics of the subset composition of follicular T helper cells (Tfh) and B lymphocytes. Expression of the HLA-B27 antigen can change the reactivity of cells of the immune system and, accordingly, their interaction and participation in the immunopathogenesis of AS. The aim of this study was to investigate the characteristics of the subset composition of Tfh and B cells in HLA-B27-positive and negative patients with AS. Material and methods. 66 patients (17 women and 49 men) aged 20–58 years with a diagnosis of AS were examined. Molecular genetic research on HLA-B27 expression was carried out using the quantitative PCR method with real-time detection. The subset composition of Tfh and B cells was studied using flow cytometry. Results. An increase in the amount of Tfh2 in the blood is observed in all patients with AS. The number of Tfh1 was reduced in HLA-B27-positive AS patients, but Tfh17 cell content was increased. Changes in the subset composition of B lymphocytes, which were found only in patients with an HLA-B27-positive form of the disease, manifest themselves primarily as an imbalance in the distribution of B cell memory. Only negative correlations of Tfh1 and Tfh17 content with “double-negative” B cell and plasmablast precursors percentage are detected in HLA-B27-negative AS patients. Tfh1 cell number correlate negatively with naïve and activated naïve B cell content in HLA-B27-positive disease, Tfh2 cell percentage – with memory B cell fraction number. CCR6+ Tfh and Tfh17 have positive regulatory effects on plasmablast precursors. Conclusions. The subset composition of Tfh characterizes the dominance in the immunopathogenesis of AS of the direction of the regulatory influence of follicular T helper cells on B lymphocytes regardless of the carriage of the HLA-B27 gene in AS patients. High levels of Tfh type 17 are also detected in HLA-B27-positive patients. The relationships between the subsets of Tfh and B cells in HLA-B27-negative AS patients characterize the presence of processes aimed at inhibiting B cells. The influence of Tfh1 is aimed at suppression of B-cell immunity in HLA-B27-positive AS while Tfh2 and Tfh17 stimulate B-cell mechanisms.
强直性脊柱炎患者滤泡 T 辅助细胞和 B 淋巴细胞的亚群组成取决于 HLA-B27 状态
由于滤泡 T 辅助细胞(Tfh)和 B 淋巴细胞亚群组成的特点,形成了与包括强直性脊柱炎(AS)在内的多种免疫病理状况有关的免疫关系。HLA-B27 抗原的表达可改变免疫系统细胞的反应性,从而改变它们之间的相互作用,并参与强直性脊柱炎的免疫发病机制。本研究旨在探讨HLA-B27阳性和阴性强直性脊柱炎患者Tfh和B细胞亚群组成的特点。材料与方法研究对象为 66 名确诊为强直性脊柱炎的 20-58 岁患者(17 名女性和 49 名男性)。采用实时检测的定量 PCR 方法对 HLA-B27 表达进行了分子遗传学研究。使用流式细胞术研究了 Tfh 细胞和 B 细胞的亚群组成。结果显示所有强直性脊柱炎患者血液中的 Tfh2 数量都有所增加。在HLA-B27阳性的强直性脊柱炎患者中,Tfh1的数量减少了,但Tfh17细胞的含量却增加了。B淋巴细胞亚群组成的变化只出现在HLA-B27阳性的强直性脊柱炎患者中,主要表现为B细胞记忆分布的不平衡。在HLA-B27阴性的强直性脊柱炎患者中,Tfh1和Tfh17的含量与 "双阴性 "B细胞和浆细胞前体的百分比仅呈负相关。在HLA-B27阳性疾病中,Tfh1细胞数量与幼稚和活化幼稚B细胞含量呈负相关,Tfh2细胞百分比与记忆B细胞分数数量呈负相关。CCR6+ Tfh和Tfh17对浆细胞前体有积极的调节作用。结论无论强直性脊柱炎患者是否携带HLA-B27基因,Tfh亚群的组成都表明,在强直性脊柱炎的免疫发病机制中,滤泡T辅助细胞对B淋巴细胞的调控作用方向占主导地位。在 HLA-B27 阳性的患者中还检测到高水平的 17 型 Tfh。在HLA-B27阴性的强直性脊柱炎患者中,Tfh亚群与B细胞之间的关系表明存在旨在抑制B细胞的过程。在 HLA-B27 阳性强直性脊柱炎患者中,Tfh1 的影响旨在抑制 B 细胞免疫,而 Tfh2 和 Tfh17 则刺激 B 细胞机制。
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