Cañete Juan D, Santiago Begoña, Cantaert Tineke, Sanmartí Raimon, Palacin Antonio, Celis Raquel, Graell Eduard, Gil-Torregrosa Beatriz, Baeten Dominique, Pablos José L
Servicio de Reumatología, Hospital 12 de Octubre, 28041 Madrid, Spain.
Ann Rheum Dis. 2007 Jun;66(6):720-6. doi: 10.1136/ard.2006.062042. Epub 2007 Jan 12.
Ectopic lymphoid neogenesis (LN) occurs in rheumatoid synovium, where it is thought to drive local antigen-dependent B cell development and autoantibody production. This process involves the expression of specific homing chemokines and the development of high endothelial venules (HEV).
To investigate whether these mechanisms occur in psoriatic arthritis (PsA) synovium, where autoantibodies have not been described and the organisation and function of B cells is not clear, and to analyse their clinical correlates.
Arthroscopic synovial biopsy specimens from patients with PsA before and after tumour necrosis factor alpha blockade were characterised by immunohistochemical analysis for T/B cell segregation, peripheral lymph node addressin (PNAd)-positive HEV, and the expression of CXCL13, CCL21 and CXCL12 chemokines in relation to the size of lymphoid aggregates.
Lymphoid aggregates of variable sizes were observed in 25 of 27 PsA synovial tissues. T/B cell segregation was often observed, and was correlated with the size of lymphoid aggregates. A close relationship between the presence of large and highly organised aggregates, the development of PNAd+ HEV, and the expression of CXCL13 and CCL21 was found. Large organised aggregates with all LN features were found in 13 of 27 tissues. LN in PsA synovitis was not related to the duration, pattern or severity of the disease. The synovial LN pattern remained stable over time in persistent synovitis, but a complete response to treatment was associated with a regression of the LN features.
LN occurs frequently in inflamed PsA synovial tissues. Highly organised follicles display the characteristic features of PNAd+ HEV and CXCL13 and CCL21 expression, demonstrating that the microanatomical bases for germinal centre formation are present in PsA. The regression of LN on effective treatment indicates that the pathogenic and clinical relevance of these structures in PsA merits further investigation.
异位淋巴组织新生(LN)发生于类风湿性滑膜炎,被认为可驱动局部抗原依赖性B细胞发育及自身抗体产生。此过程涉及特定归巢趋化因子的表达及高内皮微静脉(HEV)的发育。
研究这些机制是否存在于银屑病关节炎(PsA)滑膜,该疾病中尚未描述自身抗体,且B细胞的组织和功能尚不清楚,并分析其临床相关性。
对肿瘤坏死因子α阻断前后的PsA患者的关节镜滑膜活检标本进行免疫组织化学分析,以确定T/B细胞分离、外周淋巴结地址素(PNAd)阳性HEV以及CXCL13、CCL21和CXCL12趋化因子的表达与淋巴样聚集大小的关系。
27例PsA滑膜组织中有25例观察到大小不一的淋巴样聚集。常观察到T/B细胞分离,且与淋巴样聚集大小相关。发现大型且高度组织化的聚集、PNAd+HEV的发育以及CXCL13和CCL21的表达之间存在密切关系。27例组织中有13例发现具有所有LN特征的大型有组织聚集。PsA滑膜炎中的LN与疾病持续时间、模式或严重程度无关。在持续性滑膜炎中,滑膜LN模式随时间保持稳定,但对治疗的完全反应与LN特征的消退相关。
LN在炎症性PsA滑膜组织中频繁发生。高度组织化的滤泡显示出PNAd+HEV以及CXCL13和CCL21表达的特征,表明PsA中存在生发中心形成的微观解剖基础。LN在有效治疗后消退表明这些结构在PsA中的致病和临床相关性值得进一步研究。