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结组织显示了几种不同的免疫组织化学和分子生物学特征。胸腺淋巴滤泡被细基质纤维tenascin包围，但在相应的淋巴结中没有发现这些特征的区隔结构。在这些胸腺淋巴滤泡中，免疫组织化学，Fas抗原和p53蛋白（凋亡反应因子）的表达比胸腺其他区域少。此外，在胸腺淋巴滤泡中观察到密集但分散染色的bcl -2（凋亡抑制因子）阳性B细胞，尽管淋巴结中大部分没有阳性B细胞。通过RT-PCR方法分析，在mRNA水平上证实了抗原和蛋白的表达。有几种高度发展的胸腺淋巴样增生的患者，术前血清抗乙酰胆碱受体水平和抗体滴度均高于不发达或不发达的患者。淋巴滤泡黏附分子（LFA，ICAM）表达的记忆性和非记忆性B细胞在胸腺和淋巴结中均有相似的表达。胸腺和胸腺瘤上皮细胞使用抗ck - 17mab进行免疫化学检测。胸腺只有髓样上皮呈阳性染色。在胸腺瘤中，大约一半的病例具有阳性细胞。RT-PCR法也证实了CK-17 mRNA的表达。具有ck -17阳性细胞的胸腺瘤患者的血清抗ach - r抗体滴度高于缺乏阳性细胞的胸腺瘤患者，其残余胸腺中淋巴滤泡发育较多。ck -17阳性细胞型胸腺瘤既有多角形上皮细胞型，也有多角形梭形上皮细胞型，但与我们的预期相反，梭形上皮细胞型胸腺瘤没有阳性细胞。提示重症肌无力患者胸腺淋巴滤泡中部分产生抗体的B细胞可逃避细胞凋亡的进入。因此，它们可能存活下来并产生自身抗体。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。关于上皮细胞向胸腺瘤亚型的分化，形态学和免疫组化观察存在差异。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