Wang, Zhongya

Aims Accurate determination of histological activity in ulcerative colitis (UC) is essential given its diagnostic and prognostic importance. Data on the relationship between histology and immune cell markers are limited. We aimed to evaluate the association between histological disease activity and immune cell marker concentration in colonic biopsies from patients with UC. Methods Sigmoid colon biopsies from 20 patients with UC were retrospectively assessed using the Robarts Histopathology Index (RHI). Targeted mass spectrometry determined the concentration of 18 immune cell markers (cluster of differentiation (CD) 4, CD8, CD19, CD20, CD40, CD56, CD68, CD103, forkhead box p3 (FOXP3), human leucocyte antigen, DR alpha chain (HLA-DRA), interleukin 10 (IL-10), IL-23 subunit alpha (IL-23A), IL-23 receptor (IL-23R), IL-2 receptor alpha chain (IL-2RA), Ki67, lymphocyte-activation gene 3 (LAG-3), programmed cell death protein 1 (PD-1) and PD ligand 1 (PD-L1)). The association between RHI score and immune cell marker concentration was quantified using Spearman’s rank correlation coefficient (ρ) and related 95% CIs. Results Fourteen of the 18 immune cell marker proteins were detected, with tissue concentration ranging from 0.003 to 11.53 fmol/µg. The overall RHI score was positively correlated with CD19, CD20, CD40, FOXP3, LAG-3, PD-1 and PD-L1 concentration (ρ=0.596–0.799) and negatively correlated with CD56 concentration (ρ=−0.460). There was no significant association between RHI score and CD4, CD8, CD68, CD103, HLA-DRA or Ki67 concentration. Conclusions This study provides insight into the correlation between immune cell marker expression and histological disease activity and the possible molecular and immunological determinants underlying microscopic disease activity in UC.

SummaryBackgroundThe optimal ulcerative colitis biopsy protocol is unclear.AimTo evaluate the number of biopsies required to accurately assess microscopic disease activity in ulcerative colitisMethodsBiopsies from patients with ≥4 rectosigmoid samples, and clinical and endoscopic data, were retrospectively obtained from a prospective biobank. Histology and endoscopic videos were read blindly. A 4‐biopsy Robarts Histopathology Index (RHI) reference score, consisting of the worst item‐level ratings from four biopsies, was compared to 1‐, 2‐ and 3‐biopsy estimates. Agreement was determined using bivariate errors‐in‐variable regression analysis (acceptance interval: ±8.25). Endoscopic activity and disease location subgroup analyses were also performed.ResultsForty‐six patients had ≥4 rectosigmoid biopsies available (N = 287). The 2‐biopsy (tolerance interval: −7.66, 4.79) and 3‐biopsy (tolerance interval: −4.86, 3.46) RHI scores demonstrated acceptable agreement with 4‐biopsy scores. One‐biopsy scores demonstrated unacceptable agreement (tolerance interval: −13.99, 7.78). Mean RHI scores using the 2‐, 3‐ and 4‐biopsy approaches were similar (6.1 ± 9.6 P = 0.36; 6.8 ± 10.5, P = 0.7; 7.5 ± 11.2), whereas the 1‐biopsy estimate was lower (4.4 ± 8.1, P = 0.06). Histological remission rates were identical for the 2‐, 3‐ and 4‐biopsy methods (65.2%, P = 1.0). Subgroup analysis demonstrated that three biopsies were required in patients with endoscopically active disease. Sampling additional colonic locations yielded lower histological remission rates compared to rectosigmoid sampling alone (33.3% vs 61.9%, P = 0.1).ConclusionsA minimum of two — conservatively, three — biopsies are required to reliably assess disease activity in a single colonic segment using the RHI. Further studies are needed of endoscopically active patients and sampling locations. These results have implications for biopsy strategies in clinical trials and practice.