Adenosine Deaminase as a Useful Biomarker for Diagnosis and Monitoring of Inflammatory Bowel Disease

Abstract

Background: Inflammatory bowel disease (IBD) is a multifactorial immunologically mediated disorder characterized by repeated cycles of exacerbations and remissions. Diagnosis and monitoring of ulcerative colitis (UC) and Crohn's disease (CD) as common types of IBD require the usage of unpleasant invasive methods such as colonoscopy and cross-sectional imaging. Development of a non-invasive biomarker panel including different inflammatory parameters for evaluation of various aspects of gut inflammation and disease course is a priority task. In addition to the well-known inflammatory markers serum C-reactive protein (CRP) and fecal calprotectin (FC), adenosine deaminase (ADA) could be a promising candidate-biomarker. ADA has been shown to increase in several inflammatory conditions, but little is known about its significance in IBD. This preliminary research aims to study the serum levels of ADA in IBD patients and to evaluate its ability to adequately reflect the gut inflammatory process.

Methods: Fifty-four IBD patients (40 with UC and 14 with CD) and 50 controls were enrolled in the study. Routine laboratory parameters such as white blood cells (WBC) count, erythrocyte sedimentation rate (ESR), and CRP were used. The specific biomarker for intestinal inflammation FC was measured by sandwich immunoassay (BÜHLMANN) and ADA activity - by two-step enzyme method (BioSystems).

Results: The median [IQR: 25th - 75th percentile] ADA values in IBD patients were significantly higher than those in the controls (18.7 U/L [15.4 - 22.5] vs. 9.10 U/L [7.1 - 11.2] respectively; p < 0.0001). A significant difference was obtained when comparing median ADA values in patients with active disease (20.4 [17.8 - 25.3] U/L) with those in patients with mild form of the disease or in remission (15.3 [13.0 - 16.0]; p < 0.0001). A strong positive correlation between ADA and FC (r = 0.63; p < 0.0001) and moderate positive correlation between ADA and CRP (r = 0.46; p < 0.001) were observed. ROC-curve analysis revealed good ability of ADA to discriminate not only IBD patients from healthy individuals, but also patients with active disease and those in remission/mild form.

Conclusions: The present study revealed that ADA levels were significantly increased in IBD patients. Together with FC and CRP, ADA could be used as an effective biomarker for assessment of intestinal inflammation and as a potential indicator for disease activity.