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 disea se activity in inflammatory bowel disease (IBD). In contrast; little is kno wn about prevalence. courser and clinical significance of intestinal leakag e of larger-size serum antiproteinases in these disorders. Subjects and methods: Firstly, 23 IBD patients: (Crohn's disease. CD, n = 1 7, and ulcerative colitis, UC? n = 6) were examined at 34 independent episo des (relapse, n = 16, remission; n = 18) for parallel serum and fecal alpha (2)-macroglobulin (AMG) and AAT concentrations by standard immunonephelomet ry. and compared to SO healthy controls. From these IBD patients, secondly, a random cohort of twelve individuals (9 CD, 3 UC) was prospectively follo wed 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 co nditions. While in healthy subjects fecal AMG was demonstrated at very low levels only (less than or equal to 0.07 mg/g dws), it was found in CD and U C 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 ther correlated to Crohn's Disease Activity Index in CD patients (p = 0.05), whi le not to Clinical Activity Index in UC individuals (p = 0.46). Post hoc ev aluation of follow-up data suggested two distinct groups of LED patients ei ther with or without consistently detectable fecal AMG excretion, with the first ones exhibiting a more active clinical course than the latter ones (p less than or equal to 0.02). Conclusions: AMG is excreted in feces of healthy subjects in traces only, w hile its stool concentration is: largely increased in IBD patients where it reflects clinical disease activity. This novel stool parameter may be of p otential value in the diagnostic and prognostic management of these individ uals.