Proteomic characterisations of ulcerative colitis endoscopic biopsies associate with clinically relevant histological measurements of disease severity

Aims and methods Accurate protein measurements using formalin-fixed biopsies are needed to improve disease characterisation. This feasibility study used targeted and global mass spectrometry (MS) to interrogate a spectrum of disease severities using 19 ulcerative colitis (UC) biopsies. Results Targeted assays for CD8, CD19, CD132 (interleukin-2 receptor subunit gamma/common cytokine receptor gamma chain), FOXP3 (forkhead box P3) and IL17RA (interleukin 17 receptor A) were successful; however, assays for IL17A (interleukin 17A), IL23 (p19) (interleukin 23, alpha subunit p19) and IL23R (interleukin 23 receptor) did not permit target detection. Global proteome analysis (4200 total proteins) was performed to identify pathways associated with UC progression. Positive correlation was observed between histological scores indicating active colitis and neutrophil-related measurements (R-2=0.42-0.72); inverse relationships were detected with cell junction targets (R-2=0.49-0.71) and beta-catenin (R-2=0.51-0.55) attributed to crypt disruption. An exploratory accuracy assessment with Geboes Score and Robarts Histopathology Index cut-offs produced sensitivities/specificities of 72.7%/75.0% and 100.0%/81.8%, respectively. Conclusions Pathologist-guided MS assessments provide a complementary approach to histological scoring systems. Additional studies are indicated to verify the utility of this novel approach.

Automated summary

This study successfully used targeted mass spectrometry to analyze the expression of various cells and proteins in 19 ulcerative colitis (UC) biopsies, and performed global proteome analysis to identify pathways associated with UC progression. Positive correlations were observed between histological scores of active colitis and certain measurements, while inverse relationships were detected with other targets due to crypt disruption. An exploratory accuracy assessment showed promising sensitivities and specificities with established cut-offs. Further studies are needed to verify the utility of this novel approach.