摘要：
目的 探讨免疫组织化学指标在心脏淀粉样变性分型中的意义和价值.方法 收集中国医学科学院阜外医院1990年1月至2017年4月临床怀疑淀粉样变性的病例,行心内膜心肌活检组织和心脏移植的受体心脏,经组织学检查和刚果红染色为阳性的病例,免疫组织化学方法检测常见淀粉样物质包括甲状腺转运蛋白(TTR),免疫球蛋白 λ 轻链、κ 轻链,载脂蛋白(Apo)AⅠ、Apo AⅡ、Apo AⅣ,淀粉样物质A(AA)和β2微球蛋白在心肌活检组织中的表达.淀粉样物质的分布方式分为弥漫性细胞周间质沉积、分散性细胞周间质沉积、结节状间质沉积、心内膜沉积、动脉沉积和静脉沉积,比较不同淀粉样物质分布方式的差异.结果 共有19例患者的20份心肌组织应用免疫组织化学方法检测到淀粉样物质沉积,另外2例虽然刚果红染色阳性但应用现有抗体未检测到淀粉样物质,根据淀粉样物质的表达方式将19例分为3种,第1种(5例):心肌间质仅检测到一种淀粉样物质.第2种(6例):心肌间质检测到多种淀粉样物质,但其中一种淀粉样物质表达强度强,其余较弱或一种淀粉样物质与伴侣蛋白(Apo AⅣ)共表达.第3种(8例):心肌间质有多种淀粉样物质沉积而且表达强度均相同.前两组病例可以进行分型,分别为AL-λ、ATTR、AL-κ和AApo AⅠ型淀粉样变性.第3种表达方式因为特异性差无法进行分型,需要进行质谱或基因分析.淀粉样物质呈细胞周分布者多发生在免疫球蛋白轻链型淀粉样变性(包括AL-λ和AL-κ),较少发生于ATTR型.6例淀粉样物质在血管沉积,4例为ATTR型,2例为AL和TTR共同阳性而无法分型者.免疫组织化学方法对心脏淀粉样变性分型成功比例为11/19.结论 采用免疫组织化学方法用于心脏淀粉样变性分型时可以结合淀粉样物质的表达和分布方式、有无伴侣蛋白并结合患者其他器官的受累情况和实验室检查,可以作为心脏淀粉样变性的初步分型工具.%Objective To evaluate the sensitivity and specificity of immunohistochemistry(IHC)in the classification of cardiac amyloidosis on endomyocardial biopsy(EMB)and heart allograft. Methods Twenty cardiac tissues from 19 patients at Fuwai Hospital from January, 1990 to April, 2017 with histopathologic features of amyloidosis and Congo red staining positivity were included. IHC was performed with monoclonal antibodies against AA amyloid and polyclonal antibodies against transthyretin(ATTR), λ-light chain(AL-λ),κ-light chain(AL-κ),ApoAⅠ,ApoAⅡ,ApoAⅣand β2-microglobin. The extent of interstitial staining was evaluated by light microscopy,and three patterns were recognized;these included diffuse pericellular pattern, discrete pericellular pattern, and nodular pattern. Two patterns of vascular deposition were also noted,including arterial pattern and venous pattern. Endocardial involvement was also assessed and recorded. Results Nineteen cases were divided into three groups according to the pattern of proteins expression in specimens. The first group(5 cases)only showed single protein expression on EMB. The second group(6 cases)showed more than one protein expression,but one of them was intensely stained or any staining of any protein together with ApoA Ⅳ co-staining. The third group(8 cases)also showed more than one protein expression and all of them had intense staining. Amyloid deposits were successfully subtyped as AL-λ,ATTR,AL-κ and ApoAⅠby IHC in the former two groups with the sensitivity of 11/19. In the third group, amyloid deposits could not be subtyped by immunohistochemistry due to their poor specificity. The pericellular pattern tended to favor AL over ATTR amyloidosis and vascular deposition tended to favor ATTR. Conclusions Amyloid deposits can be reliably subtyped in diagnostic cardiac specimens using IHC. The co-deposition of chaperon proteins, the distribution of amyloid proteins and clinical features are also auxiliary to subtype cardiac amyloidosis.
