类风湿关节炎不同组织学变体中的血清细胞因子。

Serum cytokines in different histological variants of rheumatoid arthritis.

作者信息

Klimiuk P A, Sierakowski S, Latosiewicz R, Cylwik B, Skowronski J, Chwiecko J

机构信息

Department of Rheumatology and Internal Diseases, Department of Orthopedic Surgery, and Department of Pathological Anatomy, Medical University of Bialystok, Bialystok, Poland.

出版信息

J Rheumatol. 2001 Jun;28(6):1211-7.

PMID:11409111

Abstract

OBJECTIVE

Rheumatoid arthritis (RA) is characterized by an invasive and tissue destructive infiltrate of lymphocytes, macrophages, and synoviocytes formed in the joints. Its etiopathogenesis and the role of the particular morphological components of synovitis remain unclear. There is evidence that its histological heterogeneity is correlated with synovium cytokine transcription. We investigated whether the serum cytokine profile is associated with the morphological appearance of the disease.

METHODS

Tissue and serum samples were collected from 25 patients with clinically active RA and 25 with osteoarthritis (OA) as a control group. After histological analysis RA synovial biopsies were divided into 2 distinct types; 16 samples were characterized by diffuse lymphocyte infiltrates with no additional microanatomical organization. Lymphocytic aggregates with germinal center-like structures were found in 9 specimens. Serum concentrations of interferon-gamma (IFN-gamma), interleukin 12 (IL-12, p70 heterodimer), tumor necrosis factor-alpha (TNF-alpha), and IL-15 were measured by ELISA.

RESULTS

Low concentrations of IFN-gamma (p < 0.01) and IL-12 (NS) were found in RA patients' serum compared with OA controls. RA patients with follicular synovitis had lower serum concentration of IFN-gamma (p < 0.05) and IL-12 (p < 0.05) than patients with diffuse infiltrates. High concentration of TNF-alpha and IL-15 characterized RA patient serum in comparison with controls (respectively, p < 0.001 and p < 0.01). In the serum of RA patients with follicular synovitis TNF-alpha was a dominant cytokine (p < 0.01) compared to patients with diffuse disease. At TNF-alpha level > or = 44 pg/ml, 5 (56%) of 9 patients with follicular RA had such elevated values vs one of 16 diffuse patients (< 10%; p < 0.02). Only serum concentrations of TNF-alpha could effectively differentiate between patients with OA and subgroups of RA. Analysis of clinical data suggested that activity of rheumatoid disease in patients with follicular synovitis was more severe than in those with diffuse infiltrates.

CONCLUSION

The association between distinct histological appearance of rheumatoid synovitis and serum cytokine profile and diverse clinical activity of disease seems to confirm its heterogeneity.

摘要

目的

类风湿关节炎（RA）的特征是在关节处形成淋巴细胞、巨噬细胞和滑膜细胞的侵袭性及组织破坏性浸润。其发病机制以及滑膜炎特定形态学成分的作用仍不清楚。有证据表明其组织学异质性与滑膜细胞因子转录相关。我们研究了血清细胞因子谱是否与该疾病的形态学表现相关。

方法

从25例临床活动期RA患者和25例骨关节炎（OA）患者（作为对照组）中采集组织和血清样本。经过组织学分析，RA滑膜活检标本分为2种不同类型；16个样本的特征是弥漫性淋巴细胞浸润，无额外的微观解剖结构组织。在9个标本中发现有生发中心样结构的淋巴细胞聚集。通过酶联免疫吸附测定法（ELISA）测量血清中γ干扰素（IFN-γ）、白细胞介素12（IL-12，p70异二聚体）、肿瘤坏死因子-α（TNF-α）和IL-15的浓度。

结果

与OA对照组相比，RA患者血清中IFN-γ浓度较低（p < 0.01），IL-12浓度无显著差异（NS）。与弥漫性浸润患者相比，滤泡性滑膜炎的RA患者血清中IFN-γ浓度较低（p < 0.05），IL-12浓度也较低（p < 0.05）。与对照组相比，RA患者血清中TNF-α和IL-15浓度较高（分别为p < 0.001和p < 0.01）。与弥漫性疾病患者相比，在滤泡性滑膜炎的RA患者血清中TNF-α是主要细胞因子（p < 0.01）。在TNF-α水平≥44 pg/ml时，9例滤泡性RA患者中有5例（56%）有如此升高的值，而16例弥漫性患者中有1例（< 10%；p < 0.02）。只有血清TNF-α浓度能够有效区分OA患者和RA亚组。临床数据分析表明，滤泡性滑膜炎患者的类风湿疾病活动度比弥漫性浸润患者更严重。