The role of anti-endothelial cell antibody-mediated microvascular injury in the evolution of pulmonary fibrosis in the setting of collagen vascular disease
The role of anti-endothelial cell antibody-mediated microvascular injury in the evolution of pulmonary fibrosis in the setting of collagen vascular disease
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DOI：
10.1309/cnqdmhlh2wgkl32t
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发表时间：
2007-02-01
影响因子：
3.5
通讯作者：
Cowden, Daniel J.
中科院分区：
文献类型：
--
作者：
Magro, Cynthia M.;Marsh, Clay B.;Cowden, Daniel J.
我们遇到了16例结缔组织病并发肺纤维化的患者。进行常规光镜、超微结构和直接免疫荧光分析，并使用间接免疫荧光和Western blot检测循环抗体，包括内皮细胞衍生的抗体。基础疾病为皮肌炎、硬皮病、混合性结缔组织病、硬皮肌炎、干燥综合征、类风湿关节炎和抗罗相关系统性红斑狼疮。所有病例均出现一种或多种Ro、RNP Jo 1、OJ和/或核仁抗原抗体，半数病例出现抗磷脂抗体。所有活检均显示微血管损伤伴肝实质纤维化；在一些病例中，微血管损伤的超微结构表现得到证实。纤维增生类型为非特异性间质性肺炎和普通间质性肺炎。我们注意到间隔微血管中有IgG、IgA和/或补体。在6例可获得的血清样本中，间接免疫荧光内皮细胞抗体研究呈阳性，Western blot研究显示血清样本对许多内皮细胞裂解液衍生蛋白具有反应性。肺纤维化是公认的全身性结缔组织疾病的并发症，在结缔组织疾病综合征中发生，并在病理上确定了其他部位的免疫微血管损伤。类似的抗体介导的内皮细胞损伤机制可能是组织损伤和纤维化修复反应的基础。
We encountered 16 patients with connective tissue disease in whom pulmonary fibrosis developed. Routine light microscopic, ultrastructural, and direct immunofluorescent analyses were conducted, and circulating antibodies, including those of endothelial cell derivation, were assessed using indirect immunofluorescence and Western blot assays. Underlying diseases were dermatomyositis, scleroderma, mixed connective tissue disease, sclerodermatomyositis, Sjogren syndrome, rheumatoid arthritis, and anti-Ro-associated systemic lupus erythematosus. Antibodies to one or more Ro, RNP Jo 1, OJ, and/or nucleolar antigens were seen in all cases and antiphospholipid antibodies in half All biopsies revealed microvascular injury in concert with intraparenchymal fibrosis; in some cases, there were corroborative ultrastructural findings of microvascular injury. Patterns of fibroplasia represented nonspecific interstitial pneumonitis and usual interstitial pneumonitis. We noted IgG, IgA, and/or complement in the septal microvasculature. In 6 cases with available serum samples, indirect immunofluorescent endothelial cell antibody studies were positive and Western blot studies showed reactivity of serum samples to numerous endothelial cell lysate-derived proteins. Pulmonary fibrosis, a recognized complication of systemic connective tissue disease, develops in connective tissue disease syndromes with pathogenetically established immune-based microvascular injury at other sites. A similar mechanism of antibody-mediated endothelial cell injury may be the basis of the tissue injury and fibrosing reparative response.