Johannes Grimm1, Juliane Nell1, Andreas Hillenbrand2, Doris Henne-Bruns2, Julian Schmidberger3, Wolfgang Kratzer3, Beate Gruener4, Tilmann Graeter5, Michael Reinehr6, Achim Weber6, Peter Deplazes7, Peter Möller1, Annika Beck1, Thomas F E Barth1. 1. Institute of Pathology, University Ulm, Ulm, Germany. 2. Department of General and Visceral Surgery, University Hospital Ulm, Ulm, Germany. 3. Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany. 4. Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany. 5. Department of Diagnostic and Interventional Radiology, University Hospital Ulm, Ulm, Germany. 6. Department of Pathology and Molecular Pathology, University Zurich and University Hospital Zurich, Zurich, Switzerland. 7. Institute of Parasitology, University of Zurich, Zurich, Switzerland.
Abstract
BACKGROUND: 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.
BACKGROUND: 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 infectedpatients. 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 Echinococcusspp.
Authors: Michael Reinehr; Charlotte Micheloud; Felix Grimm; Philipp A Kronenberg; Johannes Grimm; Annika Beck; Juliane Nell; Cordula Meyer Zu Schwabedissen; Eva Furrer; Beat Müllhaupt; Thomas F E Barth; Peter Deplazes; Achim Weber Journal: Am J Surg Pathol Date: 2020-01 Impact factor: 6.394
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Authors: K Maeda; G F Burton; D A Padgett; D H Conrad; T F Huff; A Masuda; A K Szakal; J G Tew Journal: J Immunol Date: 1992-04-15 Impact factor: 5.422
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Authors: Thomas F E Barth; Tobias S Herrmann; Dennis Tappe; Lorenz Stark; Beate Grüner; Klaus Buttenschoen; Andreas Hillenbrand; Markus Juchems; Doris Henne-Bruns; Petra Kern; Hanns M Seitz; Peter Möller; Robert L Rausch; Peter Kern; Peter Deplazes Journal: PLoS Negl Trop Dis Date: 2012-10-25