Prediction of steroid demand in the treatment of patients with ulcerative colitis by immunohistochemical analysis of the mucosal microenvironment and immune checkpoint: role of macrophages and regulatory markers in disease severity

Abstract

We aimed to characterize the mucosal immune microenvironment and immune checkpoint of Ulcerative colitis (UC) by immunohistochemistry with correlation to prognosis: requirement of second‐line steroid‐therapy within the 2‐years after diagnosis (SR). A series of 72 cases included 56 UC, 43 non‐SR (with first‐line treatment 5‐ASA) and 13 SR, 11 infectious colitis and 5 normal colonic biopsies. Normal mucosa was characterized by low infiltrates but high BTLA and TNFRSF14. Compared to normal, UC had increased pan‐immune‐markers of CD3, CD8, FOXP3, PD‐1, CD68, CD16, CD163, PTX3 and CD11C but had decreased BTLA (P < 0.05); by GSEA analysis comparable results were found in an independent UC gene‐expression‐data set (GSE38713). Compared to infectious, UC had higher CD4, CD8, PTX3 and CD11C but lower BTLA (P < 0.05). Compared to non‐SR, SR had lower FOXP3 + Tregs (Odds‐Ratio = 0.114, P = 0.002), PD‐1 (OR = 0.176, P = 0.002) and CD163/CD68 M2‐ratio (OR, 0.019, P = 0.019) but higher CD68 + pan‐macrophages (OR = 6.034, P = 0.002). Higher Baron endoscopic and Geboes histologic disease activity scores also correlated with SR. In summary, UC was characterized by increased pan‐immune‐markers, normal TNFRSF14 and low BTLA. SR had increased CD68 + pan‐macrophages but lower immune inhibitors of FOXP3 + Tregs, PD‐1 and CD163/CD68 M2‐macrophage ratio. In conclusion, alterations of the immune homeostasis mechanisms are relevant in the UC pathogenesis and steroid‐requiring situation.

Survivin and Programmed Death Ligand-1 as Possible Players in the Pathogenesis of Ulcerative Colitis: An Immunohistochemical Study

“…Mezache et al have appreciated the high density of PDL1-positive lamina propria cells in cases UC and suggested that the nature of these cells was mainly CD8 + T lymphocytes [9]. Brusa et al pointed to the fact that PDL1 will be highly expressed in actively proliferating T and B lymphocytes [22], the fact that may explain the high expression of it in the lamina propria of UC cases as a persistently immunologically activated media destroying the colonic glands epithelial layer [23].…”

Artificial Intelligence Analysis of Gene Expression Predicted the Overall Survival of Mantle Cell Lymphoma and a Large Pan-Cancer Series

“…The original series matrix files [ 50 ] provided by the LLMPP were used for the artificial neural network analysis. The gene expression values were collapsed to symbols applying the max probe values, using the GSEA software and the gene cluster text file (*.gct) [ 52 , 53 ].…”

High PTX3 expression is associated with a poor prognosis in diffuse large B‐cell lymphoma

“…Bivariate correlation was carried out using Pearson and Spearman’s tests. The significance level was set at .05 24‐29 …”