Myasthenia gravis thymus -: Complement vulnerability of epithelial and myoid cells, complement attack on them, and correlations with autoantibody status
Myasthenia gravis thymus -: Complement vulnerability of epithelial and myoid cells, complement attack on them, and correlations with autoantibody status
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DOI：
10.2353/ajpath.2007.070240
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发表时间：
2007-09-01
影响因子：
6
通讯作者：
Willcox, Nick
中科院分区：
文献类型：
--
作者：
Leite, Maria I.;Jones, Margaret;Willcox, Nick
在早发性重症肌无力中，胸腺含有频繁的乙酰胆碱受体(AChR)特异性生发中心的淋巴结型浸润物。我们最近的证据/两步假说表明，胸腺髓质上皮细胞(表达分离的AChR亚单位)参与了浸润，胸腺肌样细胞(具有完整的AChR)参与了生发中心的形成。为了验证这一点，我们对一系列典型的全身性肌无力患者进行了补体攻击筛查。不管确切的血清学，有相当大的浸润物的胸腺出人意料地显示C5a受体和末端补体调节因子CD59在增生的上皮细胞上呈片状上调。后者还显示活化的C3b补体成分沉积，在渗入的B细胞、巨噬细胞，特别是滤泡树突状细胞上似乎更重。肌样细胞似乎对补体特别敏感；很少表达早期补体调节分子CD55、CD46或CR1，也没有检测到CD59(+)。事实上，当暴露在浸润液中，尤其是生发中心时，肌样细胞经常被标记为C1q、Ob(25%至48%)，甚至终末C9，其中一些表现出明显的损伤。这种对上皮细胞和肌样细胞的早期/持续性补体攻击有力地支持了我们的假设，特别是暴露的肌样细胞参与了生发中心的形成/自身抗体的多样化。值得注意的是，类似的变化将许多明显的AChR血清阴性患者置于与AChR血清阳性患者相同的谱中。
In early-onset myasthenia gravis, the thymus contains lymph node-type infiltrates with frequent acetylcholine receptor (AChR)-specific germinal centers. Our recent evidence/two-step hypothesis implicates hyperplastic medullary thymic epithelial cells (expressing isolated AChR subunits) in provoking infiltration and thymic myoid cells (with intact AChR) in germinal center formation. To test this, we screened for complement attack in a wide range of typical generalized myasthenia patients. Regardless of the exact serology, thymi with sizeable infiltrates unexpectedly showed patchy up-regulation of both C5a receptor and terminal complement regulator CD59 on hyperplastic epithelial cells. These latter also showed deposits of activated C3b complement component, which appeared even heavier on infiltrating B cells, macrophages, and especially follicular dendritic cells. Myoid cells appeared particularly vul-nerable to complement; few expressed the early complement regulators CD55, CD46, or CR1, and none were detectably CD59(+). indeed, when exposed to infiltrates, and especially to germinal centers, myoid cells frequently labeled for C1q, Ob (25 to 48%), or even the terminal C9, with some showing obvious damage. This early/persistent complement attack on both epithelial and myoid cells strongly supports our hypothesis, especially implicating exposed myoid cells in germinal center formation/autoantibody diversification. Remarkably, the similar changes place many apparent AChR-seronegative patients in the same spectrum as the AChR-seropositive patients.