Molecular biological and clinocopathological study on the thymuses and lymph nodes of patients with myasthenia gravis

重症肌无力患者的胸腺和淋巴组织表现出明显的免疫组织化学和分子生物学特征。胸腺淋巴滤泡周围有细小的基质纤维Tenascin，但在相应的淋巴结内未发现这些Charcteisti区域化结构。免疫组织化学显示，在这些胸腺淋巴滤泡中，Fas抗原和P53蛋白的表达频率低于胸腺的其他区域。此外，在胸腺淋巴滤泡中可见少数密集但散在染色的bc1-2(凋亡抑制因子)阳性B细胞，而在淋巴结中多数未见阳性B细胞。结果：1.RT-PCR方法分析证实了该抗原和蛋白在mRNA水平的表达。有几个高度发展的胸腺淋巴组织增生症的患者，术前血清抗Ach-R和…水平保持较高水平血清抗体滴度明显高于低度增生组和无增生组。胸腺和淋巴结中均可识别表达淋巴滤泡黏附分子(LFA、ICAM)的记忆B细胞和非记忆B细胞。用抗细胞角蛋白系列单抗中的抗CK-17mAB对胸腺和胸腺瘤的上皮细胞进行了免疫组化显示。胸腺仅髓上皮染色阳性。在胸腺瘤中，约有一半的病例有阳性细胞。RT-PCR法检测CK-17mRNA的表达。CK-17阳性胸腺瘤患者残留胸腺中抗Ach-R抗体滴度高于缺乏阳性细胞者，残留胸腺中淋巴滤泡发育较多。CK-17阳性细胞胸腺瘤均为多角形和多角形纺锤形上皮细胞型别，而梭形上皮型胸腺瘤不含阳性细胞。因此，它们可能存活下来，产生自身抗体。含有CK-17阳性上皮细胞的胸腺瘤似乎具有促进胸腺B细胞产生自身抗体的能力。对于胸腺瘤的上皮细胞分化亚型，在形态和免疫组织化学观察上有所不同。较少

Several distinct immunohistochemical and molecular biological characeristics were shown using the thymic and lymph node tissues of patients with myasthenia gravis.1. Thymic lymphoid follicles were surrounded by a fine matrix fiber tenascin, but these charcteisti compartmentalized structure was not found in the corresponding lymph nodes. In these thymic lymphoid follicles, immunohistochemically, expression of Fas antigen and p53 protein (apoptosis reacted factors) were less frequent than that in the other region of the thymus. Furthermore, Several densely but scatterd stained bc1-2 (apoptosis-depressing factor) positive B cells were observed in the thymic lymphoid follicles, although there were mostly no positive B cells in the lymph nodes. Expression of the antigen and protein were also confirmed at mRNA level through analysis using RT-PCR method.2. Patients, who had several highly developed thymic lymphoid hyperplasia, have preoperatively maintained higher level of serum anti-Ach-R an … More tibody titer than that of patients with poorly developed hyperplasia or without it.3. Population of memory and non-memory B cells of expression of adhesion molecules (LFA,ICAM) of the lymphoid follicles were similary recognized in both the thymus and lymph node.4. Epitheital cells from the thymuses and thymomas were immunochemically shown using anti-CK-17mAB among several anti-cytokeratin mAB Series. In the thymus, only medullary epithelium was positively stained. In thymomas, about half of the cases possessed positive cells. CK-17 mRNA expression in these cases were also confirmed by RT-PCR method. Patients with thymomas possessing CK-17-positive cessl showed higher level of seurm anti-Ach-R antibody titer and more developing lymphoid follicles in the residual thymuses than those lacking positive cells.CK-17-positive cell thymomas were both polygonal and polygonal-spindle shaped epithelial cell thypes, but contrary to out expection, spindle shaped epithelial cell type thymoma contained no positve cells.These results indicate that some antibody producing B cells in the thymic lymphold follicles associated with myasthenia gravis could escape the entry of apoptosis. Thus, they might survive to produce auto-antibody. Thymomas containing CK-17-positive epithelial cells seem to have a promoting ability of thymic B cells to make auto-antibodies. Regarding epithelial cell differentiation toward subtype of thymomas, there were a discrepancy in the morphological and immunohistochemical observations. Less