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dc.contributor.authorOble, Darryl A.
dc.contributor.authorMino-Kenudson, Mari
dc.contributor.authorGoldsmith, Jeffrey David
dc.contributor.authorHodi, Frank Stephen
dc.contributor.authorSeliem, Rania M.
dc.contributor.authorDranoff, Glenn
dc.contributor.authorMihm, Martin Charles
dc.contributor.authorHasserjian, Robert Paul
dc.contributor.authorLauwers, Gregory Y.
dc.date.accessioned2017-10-20T21:04:04Z
dc.date.issued2008
dc.identifier.citationOble, Darryl A., Mari Mino-Kenudson, Jeffrey Goldsmith, F. Stephen Hodi, Rania M. Seliem, Glenn Dranoff, Martin Mihm, Robert Hasserjian, and Gregory Y. Lauwers. 2008. Alpha-CTLA-4 mAb-associated panenteritis: A histologic and immunohistochemical analysis. The American Journal of Surgical Pathology 32(8): 1130–1137. doi:10.1097/PAS.0b013e31817150e3en_US
dc.identifier.issn0147-5185en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:34268567
dc.description.abstractMonoclonal antibodies (mAbs) against the cytotoxic T lymphocyte antigen-4 (CTLA-4) molecule are used as an adjuvant to experimental tumor immunization protocols in the treatment of malignant melanomas and ovarian cancers. Aside from noted early therapeutic successes, a spectrum of adverse effects, including severe gastroenteritis, has been reported. We report herein our observations of 5 patients who developed severe gastrointestinal toxicity affecting the gastric, small intestinal, and colonic mucosa. The endoscopic findings were variable, ranging from normal to diffusely erythematous and ulcerated mucosa. The constant histologic findings included a lymphoplasmacytic expansion of the lamina propria with increase in intraepithelial lymphocytes. Increased epithelial apoptosis was also a distinctive feature. Cryptitis and glandular inflammation were observed in the colon, ileum, and stomach, whereas villous blunting was present in the ileal and duodenal mucosa. Immunohistochemical analysis revealed a marked increase of all T-cell subsets (CD3+, CD4+, and CD8+) and of CD4CD25 regulatory T cells. We conclude that the panenteritis associated with injection of alpha-CTLA-4 mAbs demonstrates histology resembling autoimmune enteropathy. Furthermore, although the pathogenesis of immune dysregulation after the infusion of alpha-CTLA-4 mAbs remains unclear, we suspect that the increased number of regulatory T cells in the gastrointestinal mucosa may play a role in the pathogenicity.en_US
dc.language.isoen_USen_US
dc.publisherOvid Technologies (Wolters Kluwer Health)en_US
dc.relation.isversionofdoi:10.1097/PAS.0b013e31817150e3en_US
dash.licenseMETA_ONLY
dc.subjectcytotoxic T lymphocyte antigen-4en_US
dc.subjectmonoclonal antibodyen_US
dc.subjectautoimmune enteropathyen_US
dc.subjectiatrogenicen_US
dc.subjectimmunotherapyen_US
dc.subjectdiarrheaen_US
dc.titleAlpha-CTLA-4 mAb-associated Panenteritis: A Histologic and Immunohistochemical Analysisen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalThe American Journal of Surgical Pathologyen_US
dash.depositing.authorLauwers, Gregory Y.
dash.embargo.until10000-01-01
dc.identifier.doi10.1097/PAS.0b013e31817150e3*
workflow.legacycommentsnoap.darken_US
dash.contributor.affiliatedGoldsmith, Jeffrey
dash.contributor.affiliatedMihm, Martin
dash.contributor.affiliatedHodi, Frank
dash.contributor.affiliatedDranoff, Glenn
dash.contributor.affiliatedHasserjian, Robert
dash.contributor.affiliatedLauwers, Gregory Y.
dash.contributor.affiliatedMino-Kenudson, Mari


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