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Villitis of unknown etiology and chronic deciduitis are not associated with human papilloma virus and enterovirus infection

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Abstract

Villitis of unknown etiology (VUE) and chronic deciduitis with plasma cells (CD) are supposed to be non infectious placental lesions caused by a pathologic immune reaction similar to a host versus graft mechanism. In some investigations, infection of human trophoblastic cells with human papilloma virus (HPV) has been described, and a relationship with miscarriage, preeclampsia, and chronic inflammatory placental lesions has been suspected. Infection with enterovirus, especially Coxsackievirus, has been observed in cases with spontaneous abortion and adverse perinatal outcome, respectively. We investigated 20 cases with VUE and 30 cases with chronic deciduitis with plasma cells. The placenta specimens were analyzed for expression of HPV capsid protein by immunohistochemistry, for presence of HPV DNA via polymerase chain reaction (PCR), and for presence of enterovirus mRNA using RT-PCR, respectively. VUE was associated with maternal diseases: atopic lesions in 21%, other autoimmune diseases in 15.5%, and obesity in 31.5%, respectively. Birth weight below the 10th percentile was detected in 63% of the cases with VUE. Chronic deciduitis was associated with preterm labor and preterm premature rupture of membranes (26%). Intrauterine fetal demise occurred in 5 cases with CD (18.5%). HPV DNA, HPV capsid protein, and enterovirus mRNA were not detected in all investigated VUE or CD cases. Our investigations show that a causal role for enterovirus and human papilloma virus in the development of VUE and CD is unlikely. Therefore, HPV vaccination is unlikely to reduce the incidence of VUE and CD in the future.

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Funding

This work was supported by the Dräger Foundation (Dräger Stiftung, Lübeck, Germany).

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Authors and Affiliations

  1. Department of Pathology, Diakonissenkrankenhaus Flensburg, Knuthstraße 1, 24939, Flensburg, Germany

    Henning Feist & Jeremias Wohlschlaeger

  2. Department of Pathology, Medical School Hannover, Hannover, Germany

    Kais Hussein & Angelika Stucki-Koch

  3. Department of Pathology, University of Essen, Essen, Germany

    Thomas Hager

  4. Department of Obstetrics and Gynecology, Diakonissenkrankenhaus Flensburg, Flensburg, Germany

    Thordis Blöcker

  5. Department of Virology, Medical School Hannover, Hannover, Germany

    Albert Heim

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  1. Henning Feist
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  2. Kais Hussein
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  3. Angelika Stucki-Koch
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  4. Jeremias Wohlschlaeger
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  5. Thomas Hager
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  7. Albert Heim
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Contributions

HF: Design of the study, immunohistochemistry, collection of clinical data, sample selection, interpretation of data, manuscript preparation

KH: Design of the study, PCR, interpretation of data, manuscript preparation

ASK: PCR, interpretation of data, manuscript preparation

JW: Collection of clinical data, sample selection, interpretation of data, manuscript preparation

TH: Interpretation of data, manuscript preparation

TB: Collection of clinical data, interpretation of data, manuscript preparation

AH: Design of the study, RT-PCR, interpretation of data, manuscript preparation

Corresponding author

Correspondence to Henning Feist.

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The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki.

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The authors declare that they have no conflicts of interest.

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Feist, H., Hussein, K., Stucki-Koch, A. et al. Villitis of unknown etiology and chronic deciduitis are not associated with human papilloma virus and enterovirus infection. Virchows Arch 477, 73–81 (2020). https://doi.org/10.1007/s00428-020-02765-0

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  • DOI: https://doi.org/10.1007/s00428-020-02765-0

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