Cytotoxic mAb from rheumatic carditis recognizes heart valves and laminin
Cytotoxic mAb from rheumatic carditis recognizes heart valves and laminin
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DOI：
10.1172/jci7132
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发表时间：
2000-07-01
影响因子：
15.9
通讯作者：
Cunningham, MW
中科院分区：
文献类型：
--
作者：
Galvin, JE;Hemric, ME;Cunningham, MW
风湿热（RF）患者血清中存在与N-乙酰-β-D-葡萄糖胺（GlcNAc）和肌球蛋白交叉反应的抗链球菌抗体。然而，它们在组织损伤中的作用尚不清楚。在这项研究中，我们表明，抗GlcNAc/抗肌球蛋白单克隆抗体3.B6风湿性心脏炎患者的人内皮细胞系的细胞毒性，并与人瓣膜内皮细胞和基底膜。人心肌肌球蛋白、层粘连蛋白、GlcNAc均能抑制mAb 3.B6与瓣膜的反应性。mAb 3.B6表位定位于人心肌肌球蛋白片段中，包括重链肌球蛋白（HMM）、S1亚片段和两个轻链肌球蛋白（LMM）肽，其含有氨基酸序列KEALISSLTRGKLTYTQQ（LMM 1）和SERVQLLHSQNTSLINQK（LMM 33）。mAb 3.B6的一个新特征是其与细胞外基质蛋白层粘连蛋白的反应性，这可以解释其与瓣膜表面的反应性。与LMM 33同源的层粘连蛋白A链肽（HTQNT）抑制mAb 3.B6与人瓣膜的反应性。这些数据支持风湿性心脏炎中交叉反应抗体导致瓣膜内皮和底层基质损伤的假设。
Anti-streptococcal antibodies cross-reactive with N-acetyl-beta D-glucosamine (GlcNAc) and myosin are present in the sera of patients with rheumatic fever (RF). However, their role in tissue injury is not clear. In this study, we show that anti-GlcNAc/anti-myosin mAb 3.B6 from a rheumatic carditis patient was cytotoxic for human endothelial cell lines and reacted with human valvular endothelium and underlying basement membrane. Reactivity of mAb 3.B6 with the valve was inhibited by human cardiac myosin > laminin, GlcNAc. The mAb 3.B6 epitopes were localized in fragments of human cardiac myosin, including heavy meromyosin (HMM), the S1 subfragment, and two light meromyosin (LMM) peptides containing amino acid sequences KEALISSLTRGKLTYTQQ (LMM 1) and SERVQLLHSQNTSLINQK (LMM 33). A novel feature of mAb 3.B6 was its reactivity with the extracellular matrix protein laminin, which may explain its reactivity with the valve surface. A laminin A-chain peptide (HTQNT) that includes homology to LMM33 inhibited the reactivity of mAb 3.B6 with human valve. These data support the hypothesis that cross-reactive antibodies in rheumatic carditis cause injury at the endothelium and underlying matrix of the valve.