Evaluation of Serological Markers in Alveolar Echinococcosis Emphasizing the Correlation of PET-CTI Tracer Uptake with RecEm18 and Echinococcus-Specific IgG

Hotz, Julian Frederic; Peters, Lynn; Kapp-Schwörer, Silke; Theis, Frauke; Eberhardt, Nina; Essig, Andreas; Grüner, Beate; Hagemann, Jürgen Benjamin

doi:10.3390/pathogens11020239

Cited by 10 publications

(9 citation statements)

References 26 publications

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“…However, antibody tests are less reliable in inoperable patients and in patients after incomplete resection [ 12 ]. Furthermore, EM2-plus or Em18 ELISA are used to determine the viability of alveolar echinococcosis [ 13 , 14 ] and hence guide treatment decisions during the course of incompletely resected or inoperable disease [ 15 ]. They, however, seem insufficiently discriminant to substantiate a decision on treatment withdrawal [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

Follow-up PET/CT of alveolar echinococcosis: Comparison of metabolic activity and immunodiagnostic testing

et al. 2022

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Purpose To investigate the potential role of follow-up 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in therapy control of inoperable patients with alveolar echinococcosis. Materials and methods In this single-center retrospective cohort study, 48 PET/CT of 16 patients with confirmed alveolar echinococcosis were analysed. FDG-uptake of the most active echinococcosis manifestation was measured (i.e., maximum standardized uptake value (SUVmax) and in relation to background activity in normal liver tissue (SUVratio)) and compared to immunodiagnostic testing. For clinical patient follow-up, patient demographics, laboratory data, including E. granulosus hydatid fluid (EgHF) antibody units (AU) as well as clinical and treatment information were assessed for all patients at the time of PET/CT, and at the last recorded clinical visit. Results Metabolic activity of PET/CT measured in the echinococcosis manifestation was significantly correlated with EgHF AU (p < 0.001). The differences in metabolic activity of echinococcosis manifestations between two consecutive PET/CT examinations of the same patient and differences in EgHF AU in the respective time intervals displayed a significant positive correlation (p = 0.01). A trend for a more rapid decline in SUVratio liver over time was found in patients who stopped benzimidazole therapy versus patients who did not stop therapy (p = 0.059). Conclusion In inoperable patients with alveolar echinococcosis, the course of metabolic activity in follow-up PET/CT is associated to the course EgHF antibody levels. Both parameters may potentially be used to evaluate the course of the disease and potentially predict the duration of benzimidazole therapy.

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Section: Discussionmentioning

confidence: 99%

Follow-up PET/CT of alveolar echinococcosis: Comparison of metabolic activity and immunodiagnostic testing

et al. 2022

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“…IgG screening ELISA (Institut Virion/Serion GmbH, Würzburg, Germany) were carried out on a fully automated DS2 ELISA platform (Dynex Technologies, Chantilly, USA), as described in [ 10 ]. Em2+ ELISA (Bordier Affinity Products SA, Crissier, Switzerland) was interpreted qualitatively (positive/negative) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Laboratory assessment is essential both for the initial diagnosis and for defining response to therapy. Initially, a genus-specific ELISA serves to detect antibodies to Echinococcus spp., which are also utilized to assess the therapeutic success together with imaging markers [ 8 , 9 , 10 ]. The results of further subsequent ELISAs detecting E. multilocularis -specific antibodies to Em2+ or EM18 correlate with active disease and can therefore serve to monitor disease activity.…”

Section: Introductionmentioning

confidence: 99%

18F-FDG-PET/MR in Alveolar Echinococcosis: Multiparametric Imaging in a Real-World Setting

et al. 2022

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Recent improvements in alveolar echinococcosis (AE) therapy can provide long-term disease control, and even allow structured treatment interruption in selected cases. Imaging has a pivotal role in monitoring disease activity, with 18-fluoro-deoxyglucose positron emission and computed tomography (18F-FDG-PET/CT) in particular having proven beneficial for assessing disease activity. Repetitive regular examinations to monitor therapy response, however, can lead to substantial radiation burden. Therefore, by combining metabolic information and excellent tissue contrast in magnetic resonance imaging (MRI), PET/MR appears ideally suited for this task. Here, we retrospectively analyzed 51 AE patients that underwent 18F-FDG-PET/MR. Patients had a ‘confirmed/probable’ diagnosis in 22/29 cases according to the WHO classification. FDG uptake, diffusion restriction, and MRI morphology were evaluated. We found significant differences in FDG uptake between responders to benzimidazole therapy and progressive manifestations (SUVavg 2.7 ± 1.3 vs. 5.4 ± 2.2, p < 0.001) as well as between Kodama Types 1 and 3 (F = 9.9, p < 0.003). No significant differences were detected for ADC values or MRI morphology concerning response and no correlations were present between FDG uptake and ADC values. The mean radiation dose was 5.9–6.5 mSv. We conclude that the combination of metabolic information and MRI morphology at a low radiation dose proposes PET/MR as a suitable imaging modality for AE assessment. Longitudinal studies are needed to define the role of this imaging modality.

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“…These two antigens are immunologically most likely identical and can be used for a serological parasite-viability assessment after long-term therapy with albendazole in AE patients. A negative II/3-10 or Em18 antibody serology is correlated to a positive treatment outcome and clinical remission in combination with PET-CT ( Ammann et al., 2015 ; Deibel et al., 2022 ; Gottstein et al., 2019 ; Hotz et al., 2022 ). In immunohistochemistry with polyclonal rabbit antibodies directed against the II/3 antigen, the germinal layer and protoscoleces can be visualized.…”

Section: Introductionmentioning

confidence: 99%

Monoclonal antibody-based localization of major diagnostic antigens in metacestode tissue, excretory/secretory products, and extracellular vesicles of Echinococcus species

Kronenberg

Reinehr

Eichenberger

et al. 2023

Front. Cell. Infect. Microbiol.

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Alveolar (AE) and cystic echinococcosis (CE) are severe parasitic zoonoses caused by the larval stages of Echinococcus multilocularis and E. granulosus sensu lato, respectively. A panel of 7 monoclonal antibodies (mAbs) was selected against major diagnostic epitopes of both species. The binding capacity of the mAbs to Echinococcus spp. excretory/secretory products (ESP) was analyzed by sandwich-ELISA, where mAb Em2G11 and mAb EmG3 detected in vitro extravesicular ESP of both E. multilocularis and E. granulosus s.s. These findings were subsequently confirmed by the detection of circulating ESP in a subset of serum samples from infected hosts including humans. Extracellular vesicles (EVs) were purified, and the binding to mAbs was analyzed by sandwich-ELISA. Transmission electron microscopy (TEM) was used to confirm the binding of mAb EmG3 to EVs from intravesicular fluid of Echinococcus spp. vesicles. The specificity of the mAbs in ELISA corresponded to the immunohistochemical staining (IHC-S) patterns performed on human AE and CE liver sections. Antigenic small particles designated as ‘‘spems’’ for E. multilocularis and ‘‘spegs’’ for E. granulosus s.l. were stained by the mAb EmG3IgM, mAb EmG3IgG1, mAb AgB, and mAb 2B2, while mAb Em2G11 reacted with spems and mAb Eg2 with spegs only. The laminated layer (LL) of both species was strongly visualized by using mAb EmG3IgM, mAb EmG3IgG1, mAb AgB, and mAb 2B2. The LL was specifically stained by mAb Em2G11 in E. multilocularis and by mAb Eg2 in E. granulosus s.l. In the germinal layer (GL), including the protoscoleces, a wide staining pattern with all structures of both species was observed with mAb EmG3IgG1, mAb EmG3IgM, mAb AgB, mAb 2B2, and mAb Em18. In the GL and protoscoleces, the mAb Eg2 displayed a strong E. granulosus s.l. specific binding, while mAb Em2G11 exhibited a weak granular E. multilocularis specific reaction. The most notable staining pattern in IHC-S was found with mAb Em18, which solely bound to the GL and protoscoleces of Echinococcus species and potentially to primary cells. To conclude, mAbs represent valuable tools for the visualization of major antigens in the most important Echinococcus species, as well as providing insights into parasite-host interactions and pathogenesis.

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Evaluation of Serological Markers in Alveolar Echinococcosis Emphasizing the Correlation of PET-CTI Tracer Uptake with RecEm18 and Echinococcus-Specific IgG

Cited by 10 publications

References 26 publications

Follow-up PET/CT of alveolar echinococcosis: Comparison of metabolic activity and immunodiagnostic testing

Follow-up PET/CT of alveolar echinococcosis: Comparison of metabolic activity and immunodiagnostic testing

18F-FDG-PET/MR in Alveolar Echinococcosis: Multiparametric Imaging in a Real-World Setting

Monoclonal antibody-based localization of major diagnostic antigens in metacestode tissue, excretory/secretory products, and extracellular vesicles of Echinococcus species

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