DEFB4A/hBD2, a non-invasive serum biomarker for detection of ulcerative colitis

The ulcerative colitis (UC) is a chronic episodic relapsing, and remitting inflammatory bowel disease with increasing frequency worldwide. Along with colonoscopy, faecal calprotectin (FCP) > 150 µg/g, elevated faecal Lactoferrin or elevated CRP are now considered for diagnosis and to take treatment decision. But there are a group of patients showing either symptomatic remission with high biomarkers or active disease having no biomarker. Hence, identification of biomarker with better diagnostic potential is still required for UC patients. To determine the deregulated genes in UC, microarray analysis was employed with colonic tissue of UC and irritable bowel syndrome (IBS) as control. Pathway enrichment analysis with differentially expressed (DE) genes revealed anti-microbial peptide mediated immune response pathways might play pivotal role in UC. Subsequently, qRT-PCR validation depicted that among the DE genes, DefensinsB4A (DEFB4A/hBD2) showed highest significant alterations in UC compared to IBS control. The data was also validated by immunohistochemistry with colonic tissue from IBS and active UC, and subsequently ELISA with healthy control (HC), active UC, and UC in remission. Crohn’s disease patient was considered as other inflammatory disease. A significantly high level of DEFB4A/hBD2 was noted in the serum of active UC patients compared to HC (p < 0.001) and it was significantly reduced in patients in remission (p < 0.001). ROC analysis revealed that DEFB4A/hBD2 with more than 220.74 pg/ml level can differentiate active UC patient from HC and active UC from patients in remission with 89% and 90% sensitivity, and 95% and 77% specificity respectively. The positive predictive values were 85.4% and 83% respectively while negative predictive value was 79% in both and 95% confidence intervals were (0.88–0.98) and (0.81–0.97) respectively. These findings suggest that DEFB4A/hBD2 could serve as a potential serum diagnostic marker for active UC patients; a decrease in its level indicates remission, though further validation with a larger sample size is needed.