Grimm Johannes, Nell Juliane, Hillenbrand Andreas, Henne-Bruns Doris, Schmidberger Julian, Kratzer Wolfgang, Gruener Beate, Graeter Tilmann, Reinehr Michael, Weber Achim, Deplazes Peter, Möller Peter, Beck Annika, Barth Thomas F E
Institute of Pathology, University Ulm, Ulm, Germany.
Department of General and Visceral Surgery, University Hospital Ulm, Ulm, Germany.
PLoS Negl Trop Dis. 2020 Dec 28;14(12):e0008921. doi: 10.1371/journal.pntd.0008921. eCollection 2020 Dec.
Alveolar (AE) and cystic echinococcosis (CE) in humans are caused by the metacestode of the tapeworms Echinococcus multilocularis and Echinococcus granulosus sensu lato (s.l.). Immunohistochemistry with the monoclonal antibodies (mAb) Em2G11, specific for AE, and the mAb EmG3, specific for AE and CE, is an important pillar of the histological diagnosis of these two infections. Our aim was to further evaluate mAb EmG3 in a diagnostic setting and to analyze in detail the localization, distribution, and impact of small particles of Echinococcus multilocularis (spems) and small particles of Echinococcus granulosus s.l. (spegs) on lymph nodes.
METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the mAb EmG3 in a cohort of formalin-fixed, paraffin embedded (FFPE) specimens of AE (n = 360) and CE (n = 178). These samples originated from 156 AE-patients and 77 CE-patients. mAb EmG3 showed a specific staining of the metacestode stadium of E. multilocularis and E. granulosus s.l. and had a higher sensitivity for spems than mAb Em2G11. Furthermore, we detected spegs in the surrounding host tissue and in almost all tested lymph nodes (39/41) of infected patients. 38/47 lymph nodes of AE showed a positive reaction for spems with mAb EmG3, whereas 29/47 tested positive when stained with mAb Em2G11. Spegs were detected in the germinal centers, co-located with CD23-positive follicular dendritic cells, and were present in the sinuses. Likewise, lymph nodes with spems and spegs in AE and CE were significantly enlarged in size in comparison to the control group.
CONCLUSIONS/SIGNIFICANCE: mAb EmG3 is specific for AE and CE and is a valuable tool in the histological diagnosis of echinococcosis. Based on the observed staining patterns, we hypothesize that the interaction between parasite and host is not restricted to the main lesion since spegs are detected in lymph nodes. Moreover, in AE the number of spems-affected lymph nodes is higher than previously assumed. The enlargement of lymph nodes with spems and spegs points to an immunological interaction with the small immunogenic particles (spems and spegs) of Echinococcus spp.
人类肺泡型(AE)和囊型棘球蚴病(CE)由多房棘球绦虫和广义细粒棘球绦虫的中绦期幼虫引起。使用针对AE的单克隆抗体(mAb)Em2G11和针对AE及CE的mAb EmG3进行免疫组织化学检测,是这两种感染组织学诊断的重要支柱。我们的目的是在诊断环境中进一步评估mAb EmG3,并详细分析多房棘球绦虫小颗粒(spems)和广义细粒棘球绦虫小颗粒(spegs)在淋巴结中的定位、分布及影响。
方法/主要发现:我们在一组甲醛固定、石蜡包埋(FFPE)的AE标本(n = 360)和CE标本(n = 178)中评估了mAb EmG3。这些样本来自156例AE患者和77例CE患者。mAb EmG3对多房棘球绦虫和广义细粒棘球绦虫的中绦期幼虫显示出特异性染色,并且对spems的敏感性高于mAb Em2G11。此外,我们在受感染患者的周围宿主组织以及几乎所有测试的淋巴结(39/41)中检测到了spegs。AE患者的47个淋巴结中有38个对mAb EmG3检测spems呈阳性反应,而用mAb Em2G11染色时,47个中有29个检测呈阳性。在生发中心检测到spegs,它们与CD23阳性滤泡树突状细胞共定位,并且存在于窦中。同样,与对照组相比,AE和CE中存在spems和spegs的淋巴结在大小上显著增大。
结论/意义:mAb EmG3对AE和CE具有特异性,是棘球蚴病组织学诊断中的一种有价值的工具。基于观察到的染色模式,我们推测寄生虫与宿主之间的相互作用并不局限于主要病变部位,因为在淋巴结中检测到了spegs。此外,在AE中,受spems影响的淋巴结数量比之前认为的要多。存在spems和spegs的淋巴结肿大表明与棘球绦虫属的小免疫原性颗粒(spems和spegs)存在免疫相互作用。