类风湿关节炎患者不同亚群T滤泡辅助淋巴细胞的表达及血清IL-6、IL-17、TGF-β和MMP-3含量分析
Expression of T follicular helper lymphocytes with different subsets and analysis of serum IL-6, IL-17, TGF-β and MMP-3 contents in patients with rheumatoid arthritis.
作者信息
Sun W-K, Bai Y, Yi M-M, Wu L-J, Chen J-L, Wu D-M, Wu H-W, Wan L, Meng Y, Zhang Q-L
机构信息
School of Laboratory Medicine/Sichuan Provincial Engineering Laboratory for Prevention and Control Technology of Veterinary Drug Residue in Animal-origin Food, Chengdu Medical College, Chengdu, P.R. China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Jan;23(1):61-69. doi: 10.26355/eurrev_201901_16748.
OBJECTIVE
To investigate the expression levels of T follicular helper (Tfh) with different subsets in patients with rheumatoid arthritis (RA) and their serum interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-β (TGF-β) and matrix metalloproteinase 3 (MMP-3) contents.
PATIENTS AND METHODS
The medical records of 45 RA patients in the Department of Rheumatology and Immunology in the First Affiliated Hospital of Chengdu Medical College from January 2016 to April 2018 were retrospectively analyzed. They were divided into the RA high activity group (24 cases, group A) (DAS28 score ≥ 5.0) and RA low activity group (21 cases, group B) (3.2 < DAS28 score < 5.0). At the same time, 20 healthy subjects were selected as a control group. Flow cytometry was used to detect the expression levels of Tfh1, Tfh2 and Tfh17, enzyme-linked immunosorbent assay to detect serum IL-6, IL-17, IL-21 and MMP-3 concentrations. The correlation of Tfh cells with IL-6, IL-17, IL-21 and MMP-3 was analyzed.
RESULTS
Those of peripheral blood mononuclear cell (PBMC) Tfh2 and Tfh17 cells were significantly higher in group A than those in group B (p < 0.05). Compared with the control group, the concentrations of serum IL-6, IL-17 and MMP-3 significantly increased (p < 0.001), but that of serum TGF-β markedly decreased in group A and group B (p < 0.01). The concentrations of serum IL-6, IL-17 and MMP-3 were remarkably higher in group A than those in group B (p < 0.001), but that of serum TGF-β was significantly lower in group A than that in group B (p < 0.001). The expression level of PBMC Tfh2 cells, PBMC Tfh17 cells was positively correlated with serum IL-6, IL-17 and MMP-3. The expression levels of Tfh2 and Tfh17 cells are positively correlated with serum IL-6, IL-17 and MMP-3 concentrations, negatively correlated with serum TGF-β concentration.
CONCLUSIONS
Tfh2 and Tfh17 are expected to be new targets for immunotherapy in RA patients.
目的
探讨类风湿关节炎（RA）患者不同亚群滤泡辅助性T细胞（Tfh）的表达水平及其血清白细胞介素-6（IL-6）、白细胞介素-17（IL-17）、转化生长因子-β（TGF-β）和基质金属蛋白酶3（MMP-3）含量。
患者与方法
回顾性分析成都医学院第一附属医院风湿免疫科2016年1月至2018年4月收治的45例RA患者的病历资料。将其分为RA高活动组（24例，A组）（DAS28评分≥5.0）和RA低活动组（21例，B组）（3.2＜DAS28评分＜5.0）。同时，选取20例健康受试者作为对照组。采用流式细胞术检测Tfh1、Tfh2和Tfh17的表达水平，酶联免疫吸附测定法检测血清IL-6、IL-17、IL-21和MMP-3浓度。分析Tfh细胞与IL-6、IL-17、IL-21和MMP-3的相关性。
结果
A组外周血单个核细胞（PBMC）中Tfh2和Tfh17细胞水平显著高于B组（p＜0.05）。与对照组相比，A组和B组血清IL-6、IL-17和MMP-3浓度显著升高（p＜0.001），但血清TGF-β浓度显著降低（p＜0.01）。A组血清IL-6、IL-17和MMP-3浓度显著高于B组（p＜0.001），但A组血清TGF-β浓度显著低于B组（p＜0.001）。PBMC中Tfh2细胞、PBMC中Tfh17细胞的表达水平与血清IL-6、IL-17和MMP-3呈正相关。Tfh2和Tfh17细胞的表达水平与血清IL-6、IL-17和MMP-3浓度呈正相关，与血清TGF-β浓度呈负相关。
结论
Tfh2和Tfh17有望成为RA患者免疫治疗的新靶点。
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