Tissue cytokine patterns distinguish variants of rheumatoid synovitis.
Tissue cytokine patterns distinguish variants of rheumatoid synovitis.
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发表时间：
1997-11
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通讯作者：
P. Klimiuk;J. Goronzy;J. Björnsson;R. Beckenbaugh;C. Weyand
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作者：
P. Klimiuk;J. Goronzy;J. Björnsson;R. Beckenbaugh;C. Weyand
类风湿性关节炎（RA）是一种慢性炎症性疾病，主要表现在滑膜。组织浸润由T细胞、B细胞和巨噬细胞组成，但组织病理学表现差异很大，很少有病理特征。类风湿滑膜炎表型异质性的机制尚不清楚。为了探讨类风湿性滑膜炎的显微形态与细胞因子的原位产生之间是否存在相关性，我们对21例连续临床活动性RA患者的组织样本进行了检查。根据淋巴细胞浸润的组织，滑膜活检分为三个不同的亚组。10例以弥漫性淋巴浸润为特征，无进一步的微排列。在7个样本中，检测到有生发中心形成的淋巴样卵泡，在4个样本中，发现有肉芽肿形成。在所有标本中，用聚合酶链反应和液相杂交半定量检测干扰素(IFN)- γ、白细胞介素(IL)-4、IL-1 β、肿瘤坏死因子(TNF)- α、IL-10和转化生长因子- β 1的细胞因子转录。每种形态上定义的滑膜炎变体都显示出独特的细胞因子谱。ifn - γ、IL-4、IL-1 β和tnf - α的低水平转录是弥漫性滑膜炎的典型特征。在滤泡性滑膜炎中，ifn - γ是主要的细胞因子，IL-4几乎检测不到，而IL-10含量丰富。肉芽肿性滑膜炎表现出ifn - γ、IL-4、IL-1 β和tnf - α的高转录，可以与其他表型明显区分。为了研究滑膜病变的差异是否与宿主因素有关，我们比较了患者的临床参数。弥漫性滑膜炎见于大多数血清阴性RA患者，是病情最轻的一种。相反，类风湿性关节炎关节外扩散伴结节形成通常与肉芽肿性滑膜炎有关。总之，RA患者在滑膜浸润的组织和活动方面显示出可重复的模式。显微解剖与组织细胞因子产生的相关性表明，几种病理机制可以调节滑膜免疫反应的表达。
Rheumatoid arthritis (RA) is a chronic inflammatory disease with primary manifestations in the synovial membrane. Tissue infiltrates are composed of T cells, B cells, and macrophages, but histopathological appearances vary widely and are rarely pathognomonic. Mechanisms underlying the phenotypic heterogeneity of rheumatoid synovitis are not known. To explore whether a correlation exists between the microscopic patterns of rheumatoid synovitis and in situ production of cytokines, tissue samples from 21 consecutive patients with clinically active RA were examined. Based upon the organization of the lymphocyte infiltrate, the synovial biopsies were categorized into three distinct subsets. Ten samples were characterized by diffuse lymphoid infiltrates without further microarrangement. In seven samples, lymphoid follicles with germinal center formation were detected, and in four specimens, granuloma formation was identified. In all specimens, cytokine transcription of interferon (IFN)-gamma, interleukin (IL)-4, IL-1 beta, tumor necrosis factor (TNF)-alpha, IL-10, and transforming growth factor-beta 1 was semiquantified with polymerase chain reaction and liquid phase hybridization. Each of the morphologically defined variants of synovitis displayed a unique cytokine profile. Low-level transcription of IFN-gamma, IL-4, IL-1 beta, and TNF-alpha was typical of diffuse synovitis. In follicular synovitis, IFN-gamma was the dominant cytokine, IL-4 was virtually undetectable, and IL-10 was abundant. Granulomatous synovitis demonstrated high transcription of IFN-gamma, IL-4, IL-1 beta, and TNF-alpha and could be clearly distinguished from the other phenotypes. To investigate whether differences in the synovial lesions were related to host factors, patients were compared for clinical parameters. Diffuse synovitis was seen in most of the patients with seronegative RA, the mildest form of the disease. In contrast, extra-articular spreading of RA with nodule formation was typically associated with granulomatous synovitis. In summary, RA patients display reproducible patterns in the organization and activity of synovial infiltrates. The correlation of microanatomy with tissue cytokine production suggests that several pathomechanisms can modulate the expression of the immune response in the synovial membrane.