Structural heterogeneity of faecal alpha 1 antitrypsin shown by immunoblot analysis in patients with Crohn's disease.
Faecal alpha 1 antitrypsin was determined in 34 patients with Crohn's disease and in 19 healthy subjects by immune nephelometry. A structural analysis of faecal alpha 1 antitrypsin was carried out using immunoblot analysis under non-reducing conditions. Native serum alpha 1 antitrypsin migrated with an apparent molecular weight of 45 kDa. Proteolytic alpha 1 antitrypsin fragments (5-42 kDa) were specifically immunostained in 13/19 and 22/34 stool samples from control subjects and from patients with Crohn's disease respectively. There was a weak correlation (r = 0.47; p less than 0.02) between the molecular weight of fragmented alpha 1 antitrypsin and the faecal concentration in both groups, indicating that alpha 1 antitrypsin inhibits its own proteolysis by intestinal proteases in a dose dependent way. The incidence of polymeric forms (greater than 45 kDa) was similar in patients (10/34) and control subjects (5/19). In only one case in each group was the native serum form of alpha 1 antitrypsin found in faeces. We conclude that faecal alpha 1 antitrypsin differs structurally from the native serum form. Immunochemical measurements, therefore, reflect rather than represent faecal concentrations of alpha 1 antitrypsin. The controversial results in published reports may be partly explained by these findings. The molecular heterogeneity of faecal alpha 1 antitrypsin is not specifically associated with Crohn's disease.
Boege
F
F
Medizinische Poliklinik, University of Würzburg, FRG.
Fischbach
W
W
D000328:Adult; D003424:Crohn Disease / Q000378:metabolism*; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009391:Nephelometry and Turbidimetry; D011487:Protein Conformation; D000515:alpha 1-Antitrypsin / Q000032:analysis*
D000515:alpha 1-Antitrypsin