Alexander E L, Provost T T, Sanders M E, Frank M M, Joiner K A
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21239.
Am J Med. 1988 Oct;85(4):513-8. doi: 10.1016/s0002-9343(88)80087-1.
Central nervous system disease and vasculitis are extraglandular manifestations of Sjögren's syndrome. In our experience, central nervous system disease develops in approximately 70 percent of patients with Sjögren's syndrome and biopsy documented peripheral vasculitis. In order to further investigate the pathogenesis of central nervous system disease and its relationship to peripheral vasculitis in Sjögren's syndrome, we examined sera of patients with Sjögren's syndrome with and without focal central nervous system involvement for evidence of terminal complement pathway activation.
Patients were classified as having active focal central nervous system involvement only when they had focal neurologic deficits on physical examination, plus at least one abnormal neurodiagnostic test result. Two thirds of these patients also had cognitive or psychiatric dysfunction. Patients were classified as having peripheral vasculitis if they had clinical and histopathologic documentation of vascular inflammation. Serum SC5b-9 was measured by a sensitive enzyme-linked immunoabsorbent assay. Total hemolytic complement assay, measurement of serum C3 and C4 by radial immunodiffusion, and determination of immune complexes were performed.
Fluid-phase terminal complement complexes (SC5b-9) were detected in the sera of 25 of 30 (83 percent) patients with focal central nervous system involvement, but in only seven of 21 (33 percent) patients with Sjögren's syndrome without focal central nervous system disease (p = 0.00084 by Yates' chi-square analysis). Four of these seven patients without focal central nervous system disease, but who had serum SC5b-9, had psychiatric or cognitive dysfunction. SC5b-9 was also detected in sera from 14 of 15 (93 percent) patients with active biopsy-documented peripheral vasculitis in contrast to 18 of 36 (50 percent) patients without clinical evidence of peripheral vasculitis (p = 0.0094). Serum SC5b-9 was a more sensitive indicator of complement activation than circulating immune complex or complement assays.
These findings suggest that terminal complement activation may participate in the pathophysiology of both central nervous system and peripheral vasculitis in Sjögren's syndrome. Serum SC5b-9 appears to be a useful diagnostic indicator of vascular inflammation in Sjögren's syndrome and appears to identify those patients at risk for central nervous system complications.
中枢神经系统疾病和血管炎是干燥综合征的腺外表现。根据我们的经验，在约70%的干燥综合征且活检证实有外周血管炎的患者中会发生中枢神经系统疾病。为了进一步研究干燥综合征中枢神经系统疾病的发病机制及其与外周血管炎的关系，我们检测了有和没有局灶性中枢神经系统受累的干燥综合征患者血清中终末补体途径激活的证据。
仅当患者体格检查有局灶性神经功能缺损且至少一项神经诊断检查结果异常时，才被分类为有活动性局灶性中枢神经系统受累。这些患者中有三分之二还存在认知或精神功能障碍。如果患者有血管炎症的临床和组织病理学记录，则被分类为有外周血管炎。血清SC5b - 9通过灵敏的酶联免疫吸附测定法进行检测。进行总溶血补体测定、通过放射免疫扩散法测定血清C3和C4以及测定免疫复合物。
在30例有局灶性中枢神经系统受累的患者中，25例（83%）血清中检测到液相终末补体复合物（SC5b - 9），而在21例没有局灶性中枢神经系统疾病的干燥综合征患者中，只有7例（33%）检测到（经耶茨卡方分析，p = 0.00084）。这7例没有局灶性中枢神经系统疾病但血清中有SC5b - 9的患者中，有4例存在精神或认知功能障碍。与36例没有外周血管炎临床证据的患者中的18例（50%）相比，在15例活检证实有活动性外周血管炎的患者中，14例（93%）血清中也检测到SC5b - 9（p = 0.0094）。血清SC5b - 9比循环免疫复合物或补体检测更能敏感地指示补体激活。
这些发现提示终末补体激活可能参与干燥综合征中枢神经系统和外周血管炎的病理生理过程。血清SC5b - 9似乎是干燥综合征血管炎症的有用诊断指标，且似乎能识别有中枢神经系统并发症风险的患者。
