A COMMON PITUITARY AUTOANTIBODY IN TWO PATIENTS WITH IMMUNE CHECKPOINT INHIBITOR-MEDIATED HYPOPHYSITIS: ZCCHC8

AACE Clinical Case Reports
Amanda LeiterEmily J Gallagher

Abstract

Hypophysitis is an increasingly recognized adverse effect of immune checkpoint inhibitor (ICI) therapy for malignancy. However, the mechanisms through which ICIs induce hypophysitis are largely unknown. We aim to describe 2 cases of ICI-mediated hypophysitis and perform autoantibody profiling on serial samples from these patients to determine if common autoantibodies could be identified. We describe 2 cases of patients with metastatic urothelial cancer who received ICI therapy and subsequently developed severe fatigue, prompting a hormonal workup consistent with hypopituitarism. Patient 1 received the ICI ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4) and patient 2 received the ICI pembrolizumab (anti-programmed cell death protein 1). Both patients had serial seromic immune biomarker profiling using high-density protein arrays before and after developing hypophysitis. Once a common autoantibody was found, zinc finger CCHC-type containing 8 (ZCCHC8), we used immunohistochemistry to assess its presence in pituitary tissue. Of a limited number of increased autoantibodies detected, those to ZCCHC8 were the only common antibodies to increase at least 3-fold post-hypophysitis in both patients. Using immunohistochemistr...Continue Reading

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Citations

Jan 5, 2021·Expert Opinion on Biological Therapy·Maria V DeligiorgiDimitrios T Trafalis
Sep 1, 2021·Expert Review of Clinical Immunology·Francesco FrascaRosaria Maddalena Ruggeri

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