Table 3.
Top 15 proteins associated with escalation in treatment [anti-TNF/ciclosporin and/or surgery] and their associated biology based on the available literature
| Protein | p value | Log2 HR | Holm p value | Family/group | Cell of origin | Function/relevance in IBD |
|---|---|---|---|---|---|---|
| ITGAV | 1.01 × 10–8 | −−2.12 | 3.16 × 10–6 | Integrin signalling | NA | Known GWAS locus22 |
| IL-1RA | 7.46 × 10–8 | 1.01 | 2.33 × 10–5 | IL-1 | Macrophages and monocytes | Anti-IL1 drug in phase 2 trial in UC [ISRCTN43717130] |
| EpCAM | 5.59 × 10–7 | −1.03 | 1.74 × 10–4 | NA | Epithelial cells | Intercellular adhesion molecule, maintaining intestinal immune balance23 |
| IL-6 | 9.85 × 10–7 | 0.45 | 3.05 × 10–4 | IL-6 family | Th cells and macrophages | Pro-inflammatory response via IL1β and TNF |
| OSM | 1.45 × 10–6 | 0.89 | 4.49 × 10–4 | IL-6 | Th cells and macrophages | Pro-inflammatory response and anti-TNF non-response24 |
| HGF | 2.51 × 10–6 | 0.82 | 7.74 × 10–4 | Cytokine | Mesenchymal cells | Angiogenesis promotion and elevated levels in IBD25 |
| IL-18 | 1.01 × 10–5 | 1.18 | 3.10 × 10–3 | IL-1 family | Epithelial cells | IL-18 polymorphism associated with anti-TNF response26 |
| PSGL1 | 1.07 × 10–5 | −2.94 | 3.28 × 10–3 | Selectin family | Leukocyte and endothelial surfaces | Anti-PSGL-1 drug in Phase 1 trial to treat CD [NIH #8307272] |
| ADM | 1.16 × 10–5 | 1.02 | 3.53 × 10–3 | Calcitonin peptide superfamily | Epithelial cells | Case series of mucosal healing in refractory UC with AM therapy27 |
| CSF-1 | 1.20 × 10–5 | 1.04 | 3.64 × 10–3 | IL-34/CSF-1 family | Various immune cells | Pro-inflammatory macrophage-induced response28 |
| TNF-R1 | 1.89 × 10–5 | 1.21 | 5.74 × 10–3 | TNF family | Macrophages and dendritic cells | Pro-inflammatory TNF-mediated response |
| CCL23 | 5.38 × 10–5 | 0.81 | 0.016 | CC chemokines | Epithelial and immune cells | Neutrophil activation and leukocyte migration29 |
| IL-8 | 6.98 × 10–5 | 0.52 | 0.021 | CXC-chemokines | Epithelial cells, macrophages, monocytes | Neutrophil recruitment and pro-inflammatory response |
| CPM | 7.64 × 10–5 | −1.69 | 0.023 | Carboxy peptidases | Activated macrophages | Activated macrophage differentiating marker30 |
| IL-17D | 1.22 × 10–4 | −2.25 | 0.036 | IL-17 family | Th-17 cells | Th-17-driven pro-inflammatory cytokine |
Holm p represents p values adjusted for multiple testing. Log2 HR [hazard ratio] is the relative risk associated with a one-unit increase in expression of the relevant protein.