Subclinical gut inflammation in spondyloarthritis is associated with a pro-angiogenic intestinal mucosal phenotype

Background Vascular endothelial growth factor (VEGF-A) and placental growth factor (PlGF) are major regulators of pathological angiogenesis, which is a prominent feature of both Crohn's disease (CD) and peripheral synovitis in spondyloarthritis. Objective To investigate the presence of VEGF-A and PlGF in the gut of spondyloarthritis patients and to link this finding with subclinical gut inflammation in these patients. Methods Intestinal biopsies from healthy controls, CD patients, spondyloarthritis patients with or without subclinical gut inflammation and rheumatoid arthritis (RA) patients were stained for VEGF-A, PlGF, CD31 and vascular cell adhesion molecule 1 (VCAM-1) and digitally analysed. Results Spondyloarthritis patients with subclinical gut inflammation had markedly increased intestinal VEGF-A expression (p<0.001), mucosal vascularisation (p<0.001) and VCAM-1 expression (p<0.01) compared with healthy controls and RA patients, which, unlike in CD patients, was also seen when the gut inflammation was in a quiescent state. PlGF expression was highly increased in the subclinically inflamed gut of spondyloarthritis (p<0.01 compared with healthy controls), but not at all in CD. Conclusion A pro-angiogenic intestinal phenotype is observed in spondyloarthritis patients with quiescent chronic gut inflammation. This favours an environment for enhanced trafficking of immune cells in this subpopulation.