Neopterin Concentration as an Index of Disease Activity in Crohn’s Disease and Ulcerative Colitis

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Neopterin, a pyrazino-[2,3-d]-pyrimidine compound, is a metabolite of cyclic guanosine monophosphate that is released by activated T lymphocytes and macrophages after induction by γ interferon. We sought to determine whether neopterin concentration in stool, serum, or urine is a useful marker of disease activity in patients with Crohn's disease or ulcerative colitis. We prospectively studied 70 outpatients (33 M, 37 F, aged 39.2 ± 14.0 y) with Crohn's disease (33 clinically in remission, 37 active), 52 outpatients (29 M, 23 F, aged 39.8 ± 12.2 y) with ulcerative colitis (29 clinically in remission, 23 active), and 141 healthy control subjects. Fecal, serum, and urine samples were analyzed for neopterin concentration and other analytes of interest. The following clinical indices were calculated at enrollment: for Crohn's disease, the Capetown Index and Harvey Bradshaw Index; for ulcerative colitis, Simple Clinical Colitis Activity Index, Disease Activity Index, and endoscopic disease severity (rated on a scale of 0 to 3). Crohn's disease was considered active if the Harvey Bradshaw Index was ≥ 5, and ulcerative colitis was considered active if the Simple Clinical Colitis Activity Index was >3. Among Crohn's disease patients, fecal neopterin was higher in those with either clinically active (96.0 ng/g) or inactive (87.2 ng/g) disease than in control subjects (12.0 ng/g; P<0.05; inactive or active disease vs. controls). For ulcerative colitis patients, fecal neopterin concentration was higher in those with active (135.2 ng/g) disease than in those with inactive disease (62.7 ng/g; P<0.05) or healthy controls (12.0 ng/g; P<0.05). Neither serum nor urine neopterin concentrations were increased in patients with active inflammatory bowel disease. Nonsignificant trends toward greater fecal neopterin concentration were observed with increased colonic disease involvement, although not with endoscopic severity or clinical disease activity indices. Fecal neopterin concentration is increased in patients with clinically active or inactive Crohn's disease and in patients with clinically active ulcerative colitis when compared with controls, and therefore represents a new biomarker for disease activity.