Alpha1-antitrypsin phenotypes and anti-neutrophil cytoplasmic auto-antibodies in inflammatory bowel disease.
OBJECTIVE
Alpha1-antitrypsin (alpha1-AT) is encoded by a highly polymorphic gene with over 75 codominantly expressed alleles at the protease inhibitor (Pi) locus classified as normal, deficient, dysfunctional or null. The aim of this study was to determine in patients with inflammatory bowel disease: (i) the prevalence of anti-neutrophil cytoplasmic auto-antibodies (ANCA) and their antigen specificities; (ii) alpha1-AT Pi phenotypes; and (iii) possible associations between ANCA, disease activity and deficient alpha1-AT alleles.


METHODS
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, endoscopic and histological criteria. ANCA by indirect immunofluorescence (IIF) and Pi phenotyping by isoelectric focusing were performed for all patients. Positive IIF sera were tested in antigen-specific enzyme-linked immunosorbent assay: proteinase 3 (PR3), myeloperoxidase (MPO), lactoferrin (LF), lysozyme, human leucocyte elastase (HLE), cathepsin G and bactericidal/permeability 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 alpha1-AT alleles.


CONCLUSIONS
ANCA are more frequent in UC than CD and do not correlate with disease activity. ANCA and protease/antiprotease imbalance do not appear to modulate the clinical course of inflammatory bowel disease.
Taddei
C
C
Department of Nephrology-Clinical Immunology, Hôtel Dieu, Nantes, France.
Audrain
M A
MA
Reumaux
D
D
Sesboüe
R
R
Testa
A
A
Galmiche
J P
JP
Duthilleul
P
P
Colombel
J F
JF
Esnault
V L
VL
D000483:Alleles; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D000918:Antibody Specificity / Q000276:immunology; D001665:Binding Sites / Q000235:genetics; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology*; D007525:Isoelectric Focusing; D010641:Phenotype; D012720:Severity of Illness Index; D000515:alpha 1-Antitrypsin / Q000235:genetics*
D019268:Antibodies, Antineutrophil Cytoplasmic; D000515:alpha 1-Antitrypsin