ulcerative colitis, primary sclerosing cholangitis, and Crohn's disease
نویسندگان
چکیده
Fifty two serum samples from patients with Crohn's disease, 24 from patients with ulcerative colitis, and 12 from patients with primary sclerosing cholangitis were analysed for the presence of anti-neutrophil cytoplasm antibodies (ANCA) of IgG and IgA class by means of enzyme linked immunosorbent assays using lactoferrin, myeloperoxidase, and antigen extracted from azurophil granules, 'a antigen' (that is, an antigen preparation containing proteinase 3) as substrates. A high frequency of positive tests for IgG anti-lactoferrin antibodies was found in sera from patients with ulcerative colitis (50%) and primary sclerosing cholangitis (50%). In Crohn's disease only 4 of 52 (8%) sera had anti-lactoferrin antibodies in all four instances the sera belonged to patients with disease involving the colon. AU patients with sclerosing cholangitis and positive tests for anti-lactoferrin had ulcerative colitis. Low levels of IgG antibodies against myeloperoxidase or a antigen were also found occasionally in sera from patients with ulcerative colitis and primary sclerosing cholangitis. IgA antibodies directed against lactoferrin and a antigen (but not myeloperoxidase) were seen in all three conditions. (Gut 1993; 34: 56-62) Department of Internal Medicine, Gastroenterology and Rheumatology Clinics and Department of Medical Microbiology, Transfusion Medicine and Clinical Immunology Laboratory, Faculty of Health Sciences, University Hospital, S-581 85 Linkoping, Sweden E Peen S Almer G Bodemar B-O Ryden C Sjolin K Teile T Skogh Correspondence to: Dr Thomas Skogh, Department of Internal Medicine, Rheumatology Clinic, Faculty of Health Sciences, University Hospital, Linkoping, S-581 85, Sweden. Accepted for publication 12 June 1991 Since the description of anti-neutrophil cytoplasm antibodies (ANCA) in active Wegener's granulomatosis,' the interest in anti-granulocyte antibodies has increased vastly. ANCA is now recognised as a family of autoantibodies directed against cytoplasmic antigens, mainly lysosomal enzymes, in polymorphonuclear neutrophil leukocytes (PMNL).2 In Wegener's granulomatosis, ANCA are typically directed against proteinase 3, a serine proteinase located in azurophilic granules of human PMNL.3 Antiproteinase 3 antibodies may also occur in isolated, rapidly progressive glomerulonephritis and occasionally in systemic vasculitic conditions other than Wegener's granulomatosis.2 Antibodies directed against other lysosomal enzymes in PMNL azurophilic granules, for example myeloperoxidase and elastase, also occur in primary systemic vasculitic diseases and rapidly progressive glomerulonephritis.34 After ethanol fixation ofPMNL, proteinase 3 remains within the cytoplasmic granules, whereas myeloperoxidase and elastase become extracted and locate close to or on the cell nucleus.24 At indirect immunofluorescent microscopical determination of ANCA, anti-proteinase 3 antibodies produce a typical pancytoplasmatic granular staining pattern (C-ANCA), whereas antimyeloperoxidase and anti-elastase antibodies give rise to a blurry perinuclear staining pattern (P-ANCA) or staining of the PMNL nuclei (granulocyte specific anti-nuclear antibodies, GS-ANA).24' A detergent extract of isolated azurophil granules (a antigen)-can be used for the detection of anti-proteinase 3 antibodies (C-ANCA) by means ofenzyme linked immunosorbent assay (ELISA) but does not allow detection of anti-myeloperoxidase.5 6 Also, antibodies against lactoferrin, an iron binding protein residing in specific granules of PNML,7 produce a P-ANCA pattern owing to perinuclear/nuclear localisation of lactoferrin after ethanol fixation.8 Apart from the artifactual GS-ANA staining pattern caused by antibodies directed against nucleophilic cytoplasmic antigens, it is possible that true GS-ANAs also exist.9 Apart from the occurrence in primary systemic vasculitides and rapidly progressive glomerulonephritis, P-ANCA/GS-ANA may be seen in other disease states, for example rheumatoid arthritis without signs of vasculitis,'0 inflammatory bowel disease, and primary sclerosing cholangitis."-'5 Recent evidence favours the idea that inflammatory bowel disease may be caused by mesenteric vasculitis. I'l8 In a preliminary study of 16 frozen sera from patients with Crohn's disease we found low levels of anti-a antigen antibodies, anti-myeloperoxidase antibodies, and anti-lactoferrin antibodies in some sera.'9 The present study was done to extend these observations and to include sera from patients with ulcerative colitis and primary sclerosing cholangitis. Patients and methods
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Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis.
The presence of perinuclear antibodies against neutrophils (pANCA) has been detected recently in sera of patients with inflammatory bowel disease and primary sclerosing cholangitis. In order to evaluate their clinical significance, sera from 126 patients with inflammatory bowel disease (80 Crohn's disease and 46 ulcerative colitis and 22 patients with primary sclerosing cholangitis were examine...
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