Alpha1-antitrypsin phenotypes and anti-neutrophil cytoplasmic auto-antibodies in inflammatory bowel disease

Objectives Apha1-antitrypsin (alpha 1-AT) is encoded by a highly polymorphi c gene with over 75 codominantly expressed alleles at the protease inhibito r (Pi) locus classified as normal, deficient, dysfunctional or null. The ai m of this study was to determine in patients with inflammatory bowel diseas e: (i) the prevalence of anti-neutrophil cytoplasmic auto-antibodies (ANCA) and their antigen specificities; (ii) alpha 1-AT Pi phenotypes; and (iii) possible associations between ANCA, disease activity and deficient alpha 1- AT alleles. Design Study of 95 consecutive patients with ulcerative colitis (UC) and 63 patients with Crohn's disease (CD). Methods Diagnosis and disease activity were determined by clinical, endosco pic and histological criteria, ANCA by indirect immunofluorescence (IIF) an d Pi phenotyping by isoelectric focusing were performed for all patients, P ositive IIF sera were tested in antigen-specific enzyme-linked immunosorben t assay: proteinase 3 (PR3), myeloperoxidase (MPO), lactoferrin (LF), lysoz yme, human leucocyte elastase (HLE), cathepsin G and bactericidal/permeabil ity increasing protein (BPI). Results Sixty-one patients with UC (64.2%) and only 11 with CD (17.5%) had ANCA (P < 0.001), Antigen specificities were PR3 (7/61), MPO (3/61), LF (6/ 61), HLE (1/63) and BPI (10/61) in UC, and PR3 (2/11) and BPI (2/11) in CD. Three PiZ alleles were found, matching the prevalence in the normal French control population. No relationship was found between the presence of ANCA , antibody specificity, disease activity and deficient alpha 1-AT alleles. Conclusion ANCA are more frequent in UC than CD and do not correlate with d isease activity. ANCA and protease/ antiprotease imbalance do not appear to modulate the clinical course of inflammatory bowel disease, Eur J Gastroen terol Hepatol 11:1293-1298 (C) 1999 Lippincott Williams & Wilkins.