Fecal excretion of alpha 2-macroglobulin: a novel marker for disease activity in patients with inflammatory bowel disease.

BACKGROUND: Quantification of fecal alpha 1-antitrypsin (AAT) excretion is established for estimation of enteric protein loss and assessment of disease activity in inflammatory bowel disease (IBD). In contrast, little is known about prevalence, course, and clinical significance of intestinal leakage of larger-size serum antiproteinases in these disorders.

SUBJECTS AND METHODS: Firstly, 23 IBD patients (Crohn's disease, CD, n = 17, and ulcerative colitis, UC, n = 6) were examined at 34 independent episodes (relapse, n = 16, remission, n = 18) for parallel serum and fecal alpha 2-macroglobulin (AMG) and AAT concentrations by standard immunonephelometry, and compared to 40 healthy controls. From these IBD patients, secondly, a random cohort of twelve individuals (9 CD, 3 UC) was prospectively followed for those parameters at about monthly intervals for 7-14 (median 10.5) months.

RESULTS: The threshold of detection for fecal AMG concentration was about 0.06 mg per gram dry weight stool (mg/g dws) under the present analytical conditions. While in healthy subjects fecal AMG was demonstrated at very low levels only (< or = 0.07 mg/g dws), it was found in CD and UC patients at elevated concentrations of < 0.06-3.18 (median 0.17) and < 0.06-1.91 (median 0.40) mg/g dws, respectively. Fecal AMG contents were more increased in active IBD compared to quiescent disease (p = 0.03), and they correlated to Crohn's Disease Activity Index in CD patients (p = 0.05), while not to Clinical Activity Index in UC individuals (p = 0.46). Post hoc evaluation of follow-up data suggested two distinct groups of IBD patients either with or without consistently detectable fecal AMG excretion, with the first ones exhibiting a more active clinical course than the latter ones (p < or = 0.02).

CONCLUSIONS: AMG is excreted in feces of healthy subjects in traces only, while its stool concentration is largely increased in IBD patients where it reflects clinical disease activity. This novel stool parameter may be of potential value in the diagnostic and prognostic management of these individuals.