Strong and selective glomerular localization of CD134 ligand and TNF receptor-1 in proliferative lupus nephritis
Strong and selective glomerular localization of CD134 ligand and TNF receptor-1 in proliferative lupus nephritis
复制标题
DOI：
10.1681/asn.v1181426
复制
发表时间：
2000-08-01
影响因子：
13.6
通讯作者：
Weening, JJ
中科院分区：
文献类型：
--
作者：
Aten, J;Roos, A;Weening, JJ
CD134(OX40)是肿瘤坏死因子受体(TNFR)家族的一员，可在活化的T淋巴细胞上表达。CD134与其配体(CD134L)的相互作用参与共刺激T、B淋巴细胞活化，并参与T细胞与内皮细胞的黏附。为了探讨这种相互作用在系统性红斑狼疮(SLE)发病机制中的可能作用，对SLE患者外周血白细胞CD134和CD134L的表达进行了研究，发现SLE患者和对照组之间无显著差异。用含有CD134的重组人CD134嵌合分子检测CD134L，对狼疮性肾炎或其他肾脏疾病患者的肾活检组织进行免疫组织化学检测，发现CD134L在所有增殖性狼疮性肾炎患者中大量存在，呈颗粒状分布，主要分布在肾小球毛细血管壁上皮侧。激光共聚焦扫描显微镜显示与上皮下免疫沉积共存。在所检查的其他肾脏疾病中，包括非增殖性狼疮性肾炎，肾小球CD134L的染色均未检测到类似的模式。血管内皮细胞CD134L在不同类型的小血管炎中均有表达。CD134表达于血管周围浸润性白细胞和部分肾小管上皮细胞，但不表达于肾小球驻留细胞。对其他几个肿瘤坏死因子(R)家族成员的免疫组织学研究显示，在增生性狼疮性肾炎中，TNFR1的分布与观察到的CD134L相似。相反，TNFR2的肾小球表达在所有受检病例中都是相似的。CD134L和TNFR1在增生性狼疮性肾炎肾小球中的表达及其与上皮下免疫沉积的关系，可能对狼疮性肾炎的发病机制和诊断有一定的意义。
CD134 (OX40) is a member of the tumor necrosis factor (TNF) receptor (TNFR) family that can be expressed on activated T lymphocytes. Interaction between CD134 and its ligand (CD134L) is involved in costimulation of T and B lymphocyte activation, and in T cell adhesion to endothelium. To examine the possible role of this interaction in the pathogenesis of systemic lupus erythematosus (SLE), expression of CD134 and CD134L on peripheral blood leukocytes was studied, and no significant differences between SLE patients and control individuals were found. Immunohistology on renal biopsies from patients with lupus nephritis or other renal disorders, using a recombinant human CD134-containing chimeric molecule to detect CD134L, demonstrated the abundant presence of CD134L in all cases of proliferative lupus nephritis in a granular distribution predominantly along the epithelial side of the glomerular capillary wall. Confocal laser scanning microscopy indicated colocalization with subepithelial immune deposits. In none of the other renal disorders examined, including nonproliferative forms of lupus nephritis, was glomerular staining for CD134L detected in a similar pattern. Endothelial CD134L expression was frequently observed in different types of vasculitis. CD134 was detected on perivascular infiltrating leukocytes and on part of the tubular epithelium, but not on glomerular resident cells. Immunohistology for several other TNF(R) family members revealed in proliferative lupus nephritis a similar distribution for TNFR1 as was observed for CD134L. In contrast, glomerular expression of TNFR2 was similar in all cases examined. The glomerular presence of CD134L and TNFR1 in proliferative lupus nephritis in association with subepithelial immune deposits may be of pathogenetic significance and have diagnostic value.