Journal of internal medicine · 2018
Histopathological and immunophenotypic features of ipilimumab-associated colitis compared to ulcerative colitis.
Сравнительное исследованиеСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Adler B L, Pezhouh M K, Kim A, Luan L, Zhu Q, Gani F, Yarchoan M, Chen J, Voltaggio L, Parian A, Lazarev M, Lauwers G Y, Pawlik T M, Montgomery E A, Jaffee E, Le D T, Taube J M, Anders R A
Аннотация
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.
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.