Immune checkpoint inhibitor-associated celiac disease

Area of Science:

• Gastroenterology
• Immunology
• Oncology

Background:

• Immune checkpoint inhibitors (ICIs) can unmask celiac disease (CeD).
• Rare cases of ICI-associated celiac disease (ICI-CeD) have been reported.
• This study characterizes ICI-CeD versus ICI-associated duodenitis (ICI-Duo) and usual CeD.

Purpose of the Study:

• To compare clinicopathological and immunophenotypic features of ICI-CeD, ICI-Duo, and CeD.
• To differentiate treatment strategies for ICI-CeD and ICI-Duo.

Main Methods:

• Retrospective review of 8 ICI-CeD cases (2015-2019).
• Comparison with 9 ICI-Duo, 28 CeD, and 5 normal controls.
• Immunohistochemistry for T-cell subsets (CD3, CD8, γδ), PD-L1, and PD-1; quantification of intraepithelial lymphocytes (IELs).

Main Results:

• ICI-CeD and ICI-Duo share similar clinical (diarrhea, abdominal pain) and histological findings.
• ICI-CeD shows serological features of CeD (tTG-IgA) and responds to gluten-free diet (GFD).
• ICI-CeD IEL immunophenotyping differs from CeD but resembles ICI-Duo; PD-L1 expression is higher in ICI-CeD/ICI-Duo than CeD.

Conclusions:

• ICI-CeD is clinically and histologically similar to ICI-Duo, suggesting a variant of ICI-Duo.
• ICI-CeD differs from ICI-Duo in treatment response, often improving with GFD alone.
• Treatment for ICI-CeD should consider GFD, while ICI-Duo typically requires immunosuppression.