Histopathological and immunophenotypic features of ipilimumab-associated colitis compared to ulcerative colitis

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Abstract

Background: Use of the immune checkpoint inhibitor ipilimumab is sometimes complicated by ipilimumab-associated colitis (Ipi-AC), an immune-mediated colitis that mimics inflammatory bowel disease. Objective: We sought to characterize the histopathologic and immunophenotypic features of Ipi-AC and to directly compare these features to ulcerative colitis (UC). Methods: This is a retrospective cohort study of 22 patients with Ipi-AC, 12 patients with treatment-naïve UC and five controls with diarrhoea but normal endoscopic findings. Immunohistopathologic features were described, and quantitative immunohistochemistry (IHC) was performed for CD4, CD8, CD20, CD138 and FOXP3. Results: Endoscopic findings in both the Ipi-AC and UC groups included ulcerated, oedematous and erythematous mucosa. Involvement of the GI tract was more diffuse in Ipi-AC. As compared to UC, a smaller proportion of Ipi-AC biopsies had basal plasmacytosis (14% for Ipi-AC vs. 92% for UC, P < 0.0001) and crypt distortion (23% for Ipi-AC vs. 75% for UC, P = 0.003), whereas Ipi-AC biopsies had more apoptotic bodies in the left colon (17.6 ± 15.3 for Ipi-AC vs. 8.2 ± 4.2 for UC, P = 0.011). Cryptitis, ulcerations and crypt abscesses were common in both groups. Biopsy specimens from Ipi-AC had a lower density of CD20-positive lymphocytes than UC (275.8 ± 253.3 cells mm-2 for Ipi-AC vs. 1173.3 ± 1158.2 cells mm-2 for UC, P = 0.022) but had a similar density of CD4, CD8, CD138 and FOXP3-positive cells. Conclusions: Ipi-AC is a distinct pathologic entity with notable clinical and histopathological differences compared to UC. These findings provide insights into the pathophysiology of immune-related adverse events (iAEs) from ipilimumab therapy.

Original languageEnglish (US)
JournalJournal of Internal Medicine
DOIs
StateAccepted/In press - Jan 1 2018

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Colitis
Ulcerative Colitis
ipilimumab
Biopsy
Inflammatory Bowel Diseases
Abscess
Gastrointestinal Tract
Diarrhea
Colon
Mucous Membrane
Cohort Studies

Keywords

  • Colitis
  • Immunotherapy
  • Inflammatory bowel disease
  • Ipilimumab

ASJC Scopus subject areas

  • Internal Medicine

Cite this

@article{e6659970634f43d09d9995fb15d80d6d,
title = "Histopathological and immunophenotypic features of ipilimumab-associated colitis compared to ulcerative colitis",
abstract = "Background: Use of the immune checkpoint inhibitor ipilimumab is sometimes complicated by ipilimumab-associated colitis (Ipi-AC), an immune-mediated colitis that mimics inflammatory bowel disease. Objective: We sought to characterize the histopathologic and immunophenotypic features of Ipi-AC and to directly compare these features to ulcerative colitis (UC). Methods: This is a retrospective cohort study of 22 patients with Ipi-AC, 12 patients with treatment-na{\"i}ve UC and five controls with diarrhoea but normal endoscopic findings. Immunohistopathologic features were described, and quantitative immunohistochemistry (IHC) was performed for CD4, CD8, CD20, CD138 and FOXP3. Results: Endoscopic findings in both the Ipi-AC and UC groups included ulcerated, oedematous and erythematous mucosa. Involvement of the GI tract was more diffuse in Ipi-AC. As compared to UC, a smaller proportion of Ipi-AC biopsies had basal plasmacytosis (14{\%} for Ipi-AC vs. 92{\%} for UC, P < 0.0001) and crypt distortion (23{\%} for Ipi-AC vs. 75{\%} for UC, P = 0.003), whereas Ipi-AC biopsies had more apoptotic bodies in the left colon (17.6 ± 15.3 for Ipi-AC vs. 8.2 ± 4.2 for UC, P = 0.011). Cryptitis, ulcerations and crypt abscesses were common in both groups. Biopsy specimens from Ipi-AC had a lower density of CD20-positive lymphocytes than UC (275.8 ± 253.3 cells mm-2 for Ipi-AC vs. 1173.3 ± 1158.2 cells mm-2 for UC, P = 0.022) but had a similar density of CD4, CD8, CD138 and FOXP3-positive cells. Conclusions: Ipi-AC is a distinct pathologic entity with notable clinical and histopathological differences compared to UC. These findings provide insights into the pathophysiology of immune-related adverse events (iAEs) from ipilimumab therapy.",
keywords = "Colitis, Immunotherapy, Inflammatory bowel disease, Ipilimumab",
author = "Brittany Adler and Pezhouh, {M. K.} and Amy Kim and L. Luan and Qingfeng Zhu and F. Gani and Mark Yarchoan and J. Chen and Lysandra Voltaggio and Alyssa Parian and Mark Lazarev and Lauwers, {G. Y.} and Pawlik, {T. M.} and Montgomery, {Elizabeth A} and Elizabeth Jaffee and Dung Le and Taube, {Janis M} and Anders, {Robert A}",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/joim.12744",
language = "English (US)",
journal = "Journal of Internal Medicine",
issn = "0954-6820",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Histopathological and immunophenotypic features of ipilimumab-associated colitis compared to ulcerative colitis

AU - Adler, Brittany

AU - Pezhouh, M. K.

AU - Kim, Amy

AU - Luan, L.

AU - Zhu, Qingfeng

AU - Gani, F.

AU - Yarchoan, Mark

AU - Chen, J.

AU - Voltaggio, Lysandra

AU - Parian, Alyssa

AU - Lazarev, Mark

AU - Lauwers, G. Y.

AU - Pawlik, T. M.

AU - Montgomery, Elizabeth A

AU - Jaffee, Elizabeth

AU - Le, Dung

AU - Taube, Janis M

AU - Anders, Robert A

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Use of the immune checkpoint inhibitor ipilimumab is sometimes complicated by ipilimumab-associated colitis (Ipi-AC), an immune-mediated colitis that mimics inflammatory bowel disease. Objective: We sought to characterize the histopathologic and immunophenotypic features of Ipi-AC and to directly compare these features to ulcerative colitis (UC). Methods: This is a retrospective cohort study of 22 patients with Ipi-AC, 12 patients with treatment-naïve UC and five controls with diarrhoea but normal endoscopic findings. Immunohistopathologic features were described, and quantitative immunohistochemistry (IHC) was performed for CD4, CD8, CD20, CD138 and FOXP3. Results: Endoscopic findings in both the Ipi-AC and UC groups included ulcerated, oedematous and erythematous mucosa. Involvement of the GI tract was more diffuse in Ipi-AC. As compared to UC, a smaller proportion of Ipi-AC biopsies had basal plasmacytosis (14% for Ipi-AC vs. 92% for UC, P < 0.0001) and crypt distortion (23% for Ipi-AC vs. 75% for UC, P = 0.003), whereas Ipi-AC biopsies had more apoptotic bodies in the left colon (17.6 ± 15.3 for Ipi-AC vs. 8.2 ± 4.2 for UC, P = 0.011). Cryptitis, ulcerations and crypt abscesses were common in both groups. Biopsy specimens from Ipi-AC had a lower density of CD20-positive lymphocytes than UC (275.8 ± 253.3 cells mm-2 for Ipi-AC vs. 1173.3 ± 1158.2 cells mm-2 for UC, P = 0.022) but had a similar density of CD4, CD8, CD138 and FOXP3-positive cells. Conclusions: Ipi-AC is a distinct pathologic entity with notable clinical and histopathological differences compared to UC. These findings provide insights into the pathophysiology of immune-related adverse events (iAEs) from ipilimumab therapy.

AB - Background: Use of the immune checkpoint inhibitor ipilimumab is sometimes complicated by ipilimumab-associated colitis (Ipi-AC), an immune-mediated colitis that mimics inflammatory bowel disease. Objective: We sought to characterize the histopathologic and immunophenotypic features of Ipi-AC and to directly compare these features to ulcerative colitis (UC). Methods: This is a retrospective cohort study of 22 patients with Ipi-AC, 12 patients with treatment-naïve UC and five controls with diarrhoea but normal endoscopic findings. Immunohistopathologic features were described, and quantitative immunohistochemistry (IHC) was performed for CD4, CD8, CD20, CD138 and FOXP3. Results: Endoscopic findings in both the Ipi-AC and UC groups included ulcerated, oedematous and erythematous mucosa. Involvement of the GI tract was more diffuse in Ipi-AC. As compared to UC, a smaller proportion of Ipi-AC biopsies had basal plasmacytosis (14% for Ipi-AC vs. 92% for UC, P < 0.0001) and crypt distortion (23% for Ipi-AC vs. 75% for UC, P = 0.003), whereas Ipi-AC biopsies had more apoptotic bodies in the left colon (17.6 ± 15.3 for Ipi-AC vs. 8.2 ± 4.2 for UC, P = 0.011). Cryptitis, ulcerations and crypt abscesses were common in both groups. Biopsy specimens from Ipi-AC had a lower density of CD20-positive lymphocytes than UC (275.8 ± 253.3 cells mm-2 for Ipi-AC vs. 1173.3 ± 1158.2 cells mm-2 for UC, P = 0.022) but had a similar density of CD4, CD8, CD138 and FOXP3-positive cells. Conclusions: Ipi-AC is a distinct pathologic entity with notable clinical and histopathological differences compared to UC. These findings provide insights into the pathophysiology of immune-related adverse events (iAEs) from ipilimumab therapy.

KW - Colitis

KW - Immunotherapy

KW - Inflammatory bowel disease

KW - Ipilimumab

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U2 - 10.1111/joim.12744

DO - 10.1111/joim.12744

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C2 - 29464806

AN - SCOPUS:85044192634

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

SN - 0954-6820

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