Summary
BACKGROUND: The diagnosis of inflammatory bowel disease (IBD), particularly the differentiation between ulcerative colitis (UC) and Crohn's disease (CD), is difficult and delayed in many cases, despite invasive diagnostic tools. AIMS: To determine the presence and evaluate the diagnostic accuracy of the potential serological diagnostic markers perinuclear antineutrophil cytoplasmic antibodies (pANCA), autoantibodies to intestinal goblet cells (GAB) and autoantibodies to exocrine pancreas (PAB), together with combinations of these, in the diagnosis of IBD and differential diagnosis of UC and CD. METHODS: The presence of pANCA, GAB and PAB was determined in indirect immunofluorescence assay of serum samples from 71 patients with IBD (CD 43, UC 28) and 41 healthy controls. The antigen specificity of ANCA was determined using ELISA. RESULTS: Compared with the control group, we confirmed a statistically significant presence of pANCA (71.4%) and GAB (46.4%) in patients with UC and the presence of PAB only in patients with CD (30.2%) (P < 0.001). In healthy controls, neither PAB nor GAB was detected and pANCA was present in only 4.8%. The sensitivity, specificity and positive and negative predictive values in differentiation of IBD from healthy controls were as follows: pANCA+: 71%, 95%, 91%, 83%; GAB+: 46%, 100%, 100%, 73%; PAB+: 30%, 100%, 100%, 58%; combination of (pANCA+ or GAB+)/PAB–: 82%, 95%, 92%, 87%; and to distinguish UC from CD: pANCA+: 71%, 98%, 95%, 84%; GAB+: 46%, 98%, 93%, 74%; PAB+: 30%, 100%, 100%, 48%; (pANCA+ or GAB+)/PAB–: 82%, 98%, 96%, 89%. CONCLUSIONS: All three autoantibodies may be helpful tools in non-invasive diagnosis and differential diagnosis of UC and CD. Combination of the autoantibodies may be particularly helpful, as the diagnostic sensitivity is considerably improved.
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References
Glickman RM (1980) Inflammatory bowel disease. In: Isselbacher KJ, Adams RD, Braunwald E, Petersdorf RG, Wilson JD (eds) Harrison's principles of internal medicine, 9th edn. McGraw-Hill, New York, pp 1403–11
Kirschner BS (1995) Ulcerative colitis and Crohn's disease in children. Diagnosis and management. Ped Gastroenterol II 24: 99–117
Sanders DSA (1996) The differential diagnosis of Crohn's disease and ulcerative colitis. Baillière's Clin Gastroenterol 12: 19–33
Krause S, Meier R, Wegmann W, Spichtin H, Aenishänslin HW (1998) Difficulties in differentiating Crohn's disease and ulcerative colitis. Praxis 87: 1607–11
Khulusi S, Rhodes J (1997) Diagnostic dilemmas in colitis. J Roy Coll Phys London 31: 618–23
Cho JH, Brant SR (1998) Genetics and genetic markers in inflammatory bowel disease. Curr Opin Gastroenterol 14: 283–8
Koutrobakis I, Manousos ON, Mewwissen SGM, Pena AS (1996) Environmental risk factors in inflammatory bowel disease. Hepatogastroenterology 43: 381–93
Fiocchi C (1998) Inflammatory bowel disease: etiology and pathogenesis. Gastroenterol 115: 182–205
Schölmerich J (1996) Autoimmune Erkrankungen des Magen-Darm-Trakts. In: Peter HH, Pichler WJ (eds) Klinische Immunologie, 2. Aufl. Urban & Schwarzenberg, München Wien Baltimore, pp 532–46
Ginsburg CH, Ault KA, Falchuk ZM (1981) Monoclonal B lymphocytes in the peripheral blood of patients with inflammatory bowel disease. Gastroenterology 81: 1111–4
Das KM (1999) Relationship of extraintestinal involvements in inflammatory bowel disease: new insights into autoimmune pathogenesis. Digestive Dis Sci 44: 1–13
Broberger O, Perlmann P (1959) Autoantibodies in human ulcerative colitis. J Exp Med 110: 657–74
Shanahan F (1992) The role of autoantibodies and autoimmunity in chronic inflammatory disorders of the gut. Curr Opin Gastroenterol 8: 988–92
Stevens TR, Harley SL, Groom JS, Cambridge G, Leaker B, Blake DR, et al (1993) Anti-endothelial cell antibodies in inflammatory bowel disease. Dig Dis Sci 38: 426–32
Das KM, Dasgupta A, Mandal A, Geng X (1993) Autoimmunity to cytoskeletal protein tropomyosin: a clue to the pathogenetic mechanism for ulcerative colitis. Immunology 150: 2487–93
Abad E, Tueal C, Mirapeix E, Cuxart A (1997) Relationship between ANCA and clinical activity in inflammatory bowel disease: variation in prevalence of ANCA and evidence of heterogenity. J Autoimmun 10: 175–80
Terjung B, Herzog V, Worman HJ, Gestmann I, Bauer C, Sauerbruch T, et al (1998) Atypical antineutrophil cytoplasmic antibodies with perinuclear fluorescence in chronic inflammatory bowel diseases and hepatobiliary disorders colocalize with nuclear lamina proteins. Hepatology 28: 332–40
Stöcker W, Otte M, Ulrich S, Normann D, Stöcker K, Jantschek G (1984) Autoantikörper gegen exokrines Pankreas und gegen intestinale Becherzellen in der Diagnostik des Morbus Crohn und der Colitis ulcerosa. Dtsch Med Wschr 109: 1963–1969
Hibi T, Ohara M, Kobayashi K, Brown WR, Toda K, Takaishi H, et al (1994) Enzyme linked immunosorbent assay (ELISA) and immunoprecipitation studies on anti-goblet cell antibody using a mucin producing cell line patients with inflammatory bowel disease. Gut 35: 224–30
Folwaczny C, Noehl N, Tschöp K, Endres SP, Heldwein W, Loeschke K, et al (1997) Goblet cell autoantibodies in patients with inflammatory bowel disease and their first-degree relatives. Gastroenterol 133: 101–6
Takaishi H, Ohara S, Hotta K, Yajima T, Kanai T, Inoue N, et al (2000) Circulating autoantibodies against purified colonic mucin in ulcerative colitis. J Gastroenterol 35: 20–7
Stöcker W, Otte M, Ulrich S, Normann D, Finkbeiner H, Stöcker K, et al (1987) Autoimmunity to pancreatic juice in Crohn's disease. J Gastroenterol 22[Suppl 139]: 41–52
Sasse EA (1996) Reference intervals and clinical decision limits. In: Kaplan LA, Pesce AJ (eds) Clinical chemistry: theory, analysis, correlation, 3rd edn. Mosby-Year Book Inc., St Louis, pp 365–81
Falk RJ, Jenette JC (1988) Antineutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and crescentic glomerulonephritis. N Engl J Med 318: 1651–7
Peeters M, Joossens S, Vermeire SV, Vlietinck R, Bossuyt X, Rutgeerts P (2001) Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease. Am J Gastroenterol 96: 730–4
Roozendaal C, Pogany K, Horst G, Jagt TG, Kleibeuker JH, Nelis GF, et al (1999) Does analysis of the antigenic specificities of anti-neutrophil cytoplasmic antibodies contribute to their clinical significance in the inflammatory bowel diseases? Scand J Gastroenterol 34: 1123–31
Radice A, Vecchi M, Bianchi MB, Sinico RA (2000) Contribution of immunofluorescence to the identification and characterization of anti-neutrophil cytoplasmic autoantibodies. The role of different fixatives. Clin Exp Rheumatol 18: 707–12
Eggena M, Cohavy O, Parseghian MH, Hamkalo BA, Clemens D, Targan SR, et al (2000) Identification of histone H1 as a cognate antigen of the ulcerative colitis-associated marker antibody pANCA. J Autoimmun 14: 83–97
Sobajima J, Ozaki S, Osakada F, Uesugi H, Shirakawa H, Yoshida M, et al (1997) Novel autoantigens of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) in ulcerative colitis: non-histone chromosomal proteins, HMG1 and HMG2. Clin Exp Immunol 107: 135–40
Mallolas J, Esteve M, Rius E, Cabré E, Gassull MA (2000) Antineutrophil antibodies associated with ulcerative colitis interact with the antigen(s) during the process of apoptosis. Gut 47: 74–8
Wiik A (2002) Neutrophil-specific autoantibodies in chronic inflammatory bowel diseases. Autoimmun Rev 1: 67–72
Sobajima J, Ozaki S, Okazaki T, Osakada F, Sumita S, Mori K, et al (1996) Anti-neutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis: anti-cathepsin G and a novel antibody correlate with a refractory type. Clin Exp Immunol 105: 120–4
Yang P, Bohr J, Tysk C, Danielsson D, Järnerot G (1996) Antineutrophil cytoplasmic antibodies in inflammatory bowel disease and collagenous colitis: no association with lactoferrin, β-glucorinidase, myeloperoxidase, or proteinase 3. Inflamm Dis 2: 173–7
Kuwana T, Sato Y, Saka M, Kondo Y, Miyata M, Obara K, et al (2000) Anti-cathepsin G antibodies in the sera of patients with ulcerative colitis. J Gastroenterol 35: 682–9
Seibold F, Weber P, Jenss H, Wiedmann KH (1991) Antibodies to a trypsin sensitive pancreatic antigen in chronic inflammatory bowel disease: specific markers for a subgroup of patient with Crohn's disease. Gut 32: 1192–7
Goischke EM, Zilly W (1992) Klinische Bedeutung organspezifische Antikörper bei Colitis ulcerosa und Morbus Crohn. Z Gastroenterol 30: 319–24
Seibold F, Mörk H, Tanza S, Müller, Holzhüter C, Weber P, et al (1997) Pancreatic autoantibodies in Crohn's disease: a family study. Gut 40: 481–4
Quinton JF, Sendid B, Reumaux D, Duthilleul P, Cortot A, Grandbastien B, et al (1998) Anti-Saccharomices cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut 42: 788–91
Ruemmele FM, Targan SR, Levy G, et al (1998) Diagnostic accuracy of serological assays in pediatric inflammatory bowel disease. Gastroenterol 115: 822–9
Dietrich W, Ehnis T, Bauer M, Donner P, Volta U, Ricken EO, et al (1997) Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 3: 797–801
Unger F (2008) Health is wealth – Toward a European lead market in health care. Acta Medico-Biotechnica 1: 11–8
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Homšak, E., Mičetić-Turk, D. & Božič, B. Autoantibodies pANCA, GAB and PAB in inflammatory bowel disease: prevalence, characteristics and diagnostic value. Wien Klin Wochenschr 122 (Suppl 2), 19–25 (2010). https://doi.org/10.1007/s00508-010-1344-y
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DOI: https://doi.org/10.1007/s00508-010-1344-y