IMMUNOGLOBULIN-M ANTIBODIES PRESENT IN THE ACUTE PHASE OF KAWASAKI SYNDROME LYSE CULTURED VASCULAR ENDOTHELIAL-CELLS STIMULATED BY GAMMA INTERFERON
IMMUNOGLOBULIN-M ANTIBODIES PRESENT IN THE ACUTE PHASE OF KAWASAKI SYNDROME LYSE CULTURED VASCULAR ENDOTHELIAL-CELLS STIMULATED BY GAMMA INTERFERON
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DOI：
10.1172/jci112454
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发表时间：
1986-05-01
影响因子：
15.9
通讯作者：
POBER, JS
中科院分区：
文献类型：
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作者：
LEUNG, DYM;COLLINS, T;POBER, JS
川崎综合征(KS)以弥漫性血管炎和显著的T细胞和B细胞活化为特征。本研究测定了16例活动期KS患者、15例KS恢复期患者和19例年龄匹配的对照组血清对111In标记的人脐静脉内皮细胞(HUVE)的补体依赖性细胞毒活性。KS患者血清和对照组血清对标准条件下培养的HUVE细胞均无细胞毒作用。由于激活的T细胞(如存在于急性KS的T细胞)分泌γ-干扰素，我们还检测了急性KS的血清对预先与γ-干扰素孵育的HUVE细胞的影响。我们在此报告，急性KS患者血清中的免疫球蛋白M(IgM)抗体可显著(P<；0.01)杀死经γ-干扰素处理的HUVE细胞。用白细胞介素2、γ-干扰素或β-干扰素预处理不能使HUVE易与急性KS血清溶解。观察到的效果不是通过免疫复合体介导的。急性KS中的细胞毒抗体似乎是针对γ-干扰素处理的HUVE细胞上存在的诱导性单态抗原决定簇，而不是针对对照或伽玛-干扰素处理的自体人真皮成纤维细胞(HDF)。同样，急性KS血清也能诱导γ-干扰素处理的人隐静脉内皮细胞(HSVE)的裂解，但不能诱导γ-干扰素处理的人隐静脉平滑肌(HSVSM)细胞的裂解。由于γ-干扰素诱导HDF、HUVE、HSVE和HSVSM细胞表达相同水平的I类和II类主要组织相容性复合体(MHC)抗原，我们的结果提示，急性KS的抗内皮细胞抗体针对的是γ-干扰素诱导的分子，而不是MHC决定簇。人类B细胞或单核细胞未能吸收抗内皮细胞活性，进一步证实了这些观察结果。由于大多数血管炎，包括急性KS，都以显著的免疫激活和淋巴因子的分泌为特征，针对γ-干扰素诱导的内皮细胞抗原的抗体可能是血管损伤的一般机制。
Kawasaki syndrome (KS) is characterized by diffuse vasculitis and marked T cell and B cell activation. In this study, sera from 16 patients with acture KS, 15 patients in the covalescent phase of KS, and 19 age-matched controls were assessed for complement dependent cytotoxic activity against 111In-labeled human umbilical vein endothelial (HUVE) cells. Neither sera from patients with KS nor sera from controls had cytotoxic effects on HUVE cells cultivated under standard conditions. Since activated T cells such as those present in acute KS secrete gamma interferon (.gamma.-IFN), we also examined the effects of sera from acute KS on HUVE cells preincubated with .gamma.-IFN. We report here that immunoglobulin M (IgM) antibodies in sera from patients with acute KS cause significant (P < 0.01) killing of .gamma.-IFN-treated HUVE cells. Pretreatment with interleukin 2, .gamma.-IFN, or .beta.-IFN failed to render HUVE susceptible to lysis with acute KS sera. The observed effects were not mediated via immune complexes. The cytotoxic antibodies in acute KS seem to be directed against inducible monomorphic antigenic determinants present on .gamma.-IFN-treated HUVE cells but not on control or .gamma.-IFN treated autologous human dermal fibroblasts (HDF). Similarly, acute KS sera also induced lysis of .gamma.-IFN-treated human saphenous vein endothelial (HSVE) cells but not .gamma.-IFN treated human saphenous vein smooth muscle (HSVSM) cells. Since .gamma.-IFN induces the same level of class I and class II major histocompatibility complex (MHC) antigen expression on HDF, HUVE, HSVE, and HSVSM cells, our results suggest that the anti-endothelial cell antibodies in acute KS are directed to .gamma.-IFN-inducible molecules other than MHC determinants. These observations are further substantiated by the failure of human B cells or monocytes to absorb the anti-endothelial cell activity. Since most vasculitides, including acute KS, are characterized both by marked immune activation and the secretion of lymphokines, antibodies directed to .gamma.-IFN-inducible endothelial cell antigens may represent a general mechanism for vascular injury.