Anti-high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1/HMGB2) antibodies and anti-Saccharomyces cerevisiae antibodies (ASCA): accuracy in differentially diagnosing UC and CD and correlation with inflammatory bowel disease phenotype
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The development of a supportive diagnostic method has long been required to differentially diagnose ulcerative colitis (UC) and Crohn’s disease (CD). Several antibodies circulate in the sera of patients with inflammatory bowel disease. We previously identified the high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1 and HMGB2) as novel antigens of perinuclear type anti-neutrophil cytoplasmic antibodies (pANCA) and discovered anti-HMGB1/HMGB2 antibodies in sera from patients with UC. Here, we evaluated the ability of anti-HMGB1/HMGB2 antibodies combined with anti-Saccharomyces cerevisiae antibodies (ASCA) to differentially diagnose UC and CD.
We measured titers of anti-HMGB1/HMGB2 antibodies and ASCA in the sera of 213 patients with UC and 93 with CD, using enzyme-linked immunosorbent assays.
Among the patients with UC, 26.8% were positive for anti-HMGB1/HMGB2 antibodies, with 85.0% specificity towards CD and a positive predictive value of 80.3%. Corticosteroids significantly suppressed the titer of anti-HMGB1/HMGB2 antibodies. Among the patients with CD, 24.7% were positive for ASCA, with 96.2% specificity towards UC and a positive predictive value of 74.2%. Interestingly, the positivity rate of anti-HMGB/HMGB2 antibodies was higher (35.7%) in patients with the ileitis type of CD than in patients with CD in the colon (6.2%; significant difference, P < 0.01). The specificity of anti-HMGB1/HMGB2 antibodies in UC for CD in the colon was 93.8%.
CD in the colon and UC can be differentially diagnosed using anti-HMGB/HMGB2 antibodies combined with ASCA.
- Hibi T, Ohara M, Kobayashi K, Brown WR, Toda K, Takaishi H, et al. Enzyme linked immunosorbent assay (ELISA) and immunoprecipitation studies on anti-goblet cell antibody using a mucin producing cell line in patients with inflammatory bowel disease. Gut. 1994;35:224–30. CrossRef
- Takaishi H, Ohara S, Hotta K, Yajima T, Kanai T, Inoue N, et al. Circulating autoantibodies against purified colonic mucin in ulcerative colitis. J Gastroenterol. 2000;35:20–7. CrossRef
- Das KM, Dasgupta A, Mandal A, Geng X. Autoimmunity to cytoskeletal protein tropomyosin. A clue to the pathogenetic mechanism for ulcerative colitis. J Immunol. 1993;150:2487–93.
- Duerr RH, Targan SR, Landers CJ, Sutherland LR, Shanahan F. Anti-neutrophil cytoplasmic antibodies in ulcerative colitis. Comparison with other colitides/diarrheal illnesses. Gastroenterology. 1991;100:1590–6.
- Lassoued S, Sixou L, Oksman F, Pages M, Fournie A. Antineutrophil cytoplasmic antibodies and antibodies to myeloperoxidase in rheumatoid arthritis. Arthritis Rheum. 1991;34:1069–70. CrossRef
- Halbwachs-Mecarelli L, Nusbaum P, Noel LH, Reumaux D, Erlinger S, Grunfeld JP, et al. Antineutrophil cytoplasmic antibodies (ANCA) directed against cathepsin G in ulcerative colitis, Crohn’s disease and primary sclerosing cholangitis. Clin Exp Immunol. 1992;90:79–84. CrossRef
- Goldschmeding R, van der Schoot CE, ten Bokkel Huinink D, Hack CE, van den Ende ME, Kallenberg CG, et al. Wegener’s granulomatosis autoantibodies identify a novel diisopropylfluorophosphate-binding protein in the lysosomes of normal human neutrophils. J Clin Invest. 1989;84:1577–87. CrossRef
- Sobajima J, Ozaki S, Osakada F, Uesugi H, Shirakawa H, Yoshida M, et al. Novel autoantigens of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) in ulcerative colitis: non-histone chromosomal proteins, HMG1 and HMG2. Clin Exp Immunol. 1997;107:135–40. CrossRef
- Lotze MT, Tracey KJ. High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol. 2005;5:331–42. CrossRef
- Muller S, Ronfani L, Bianchi ME. Regulated expression and subcellular localization of HMGB1, a chromatin protein with a cytokine function. J Intern Med. 2004;255:332–43. CrossRef
- Waga S, Mizuno S, Yoshida M. Chromosomal protein HMG1 removes the transcriptional block caused by the cruciform in supercoiled DNA. J Biol Chem. 1990;265:19424–8.
- Shirakawa H, Tsuda K, Yoshida M. Primary structure of non-histone chromosomal protein HMG2 revealed by the nucleotide sequence. Biochemistry. 1990;29:4419–23. CrossRef
- Melloni E, Sparatore B, Patrone M, Pessino A, Passalacqua M, Pontremoli S. Extracellular release of the ‘differentiation enhancing factor’, a HMG1 protein type, is an early step in murine erythroleukemia cell differentiation. FEBS Lett. 1995;368:466–70. CrossRef
- Passalacqua M, Zicca A, Sparatore B, Patrone M, Melloni E, Pontremoli S. Secretion and binding of HMG1 protein to the external surface of the membrane are required for murine erythroleukemia cell differentiation. FEBS Lett. 1997;400:275–9. CrossRef
- Weir HM, Kraulis PJ, Hill CS, Raine AR, Laue ED, Thomas JO. Structure of the HMG box motif in the B-domain of HMG1. EMBO J. 1993;12:1311–9.
- Sobajima J, Ozaki S, Uesugi H, Osakada F, Inoue M, Fukuda Y, et al. High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis. Gut. 1999;44:867–73. CrossRef
- Andersson U, Erlandsson-Harris H. HMGB1 is a potent trigger of arthritis. J Intern Med. 2004;255:344–50. CrossRef
- Uesugi H, Ozaki S, Sobajima J, Osakada F, Shirakawa H, Yoshida M, et al. Prevalence and characterization of novel pANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic diseases. J Rheumatol. 1998;25:703–9.
- Sobajima J, Ozaki S, Uesugi H, Osakada F, Shirakawa H, Yoshida M, et al. Prevalence and characterization of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) directed against HMG1 and HMG2 in ulcerative colitis (UC). Clin Exp Immunol. 1998;111:402–7. CrossRef
- Sonnenberg A. Occupational mortality of inflammatory bowel disease. Digestion. 1990;46:10–8. CrossRef
- Main J, McKenzie H, Yeaman GR, Kerr MA, Robson D, Pennington CR, et al. Antibody to Saccharomyces cerevisiae (bakers’ yeast) in Crohn’s disease. BMJ. 1988;297:1105–6. CrossRef
- Sendid B, Colombel JF, Jacquinot PM, Faille C, Fruit J, Cortot A, et al. Specific antibody response to oligomannosidic epitopes in Crohn’s disease. Clin Diagn Lab Immunol. 1996;3:219–26.
- Joossens S, Reinisch W, Vermeire S, Sendid B, Poulain D, Peeters M, Geboes K, Bossuyt X, Vandewalle P, Oberhuber G, Vogelsang H, Rutgeerts P, Colombel JF. The value of serologic markers in indeterminate colitis: a prospective follow-up study. Gastroenterology. 2002;122:1242–7. CrossRef
- Quinton JF, Sendid B, Reumaux D, Duthilleul P, Cortot A, Grandbastien B, et al. Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut. 1998;42:788–91. CrossRef
- Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2–6. (discussion 16–9). CrossRef
- Marion JF, Rubin PH, Present DH. Differential diagnosis of chronic ulcerative colitis and Crohn’s disease. In: Kirsner JB, editor. Inflammatory bowel disease. 5th ed. Philadelphia: WB Sauders; 2000.
- Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994;330:1841–5. CrossRef
- Winship DH, Summers RW, Singleton JW, Best WR, Becktel JM, Lenk LF, et al. National Cooperative Crohn’s Disease Study: study design and conduct of the study. Gastroenterology. 1979;77:829–42.
- Wiik A. Delineation of a standard procedure for indirect immunofluorescence detection of ANCA. APMIS Suppl. 1989;6:12–3.
- Charles LA, Falk RJ, Jennette JC. Reactivity of antineutrophil cytoplasmic autoantibodies with mononuclear phagocytes. J Leukoc Biol. 1992;51:65–8.
- Barclay GR, McKenzie H, Pennington J, Parratt D, Pennington CR. The effect of dietary yeast on the activity of stable chronic Crohn’s disease. Scand J Gastroenterol. 1992;27:196–200. CrossRef
- Hisabe T, Matsui T, Sakurai T, Murakami Y, Tanabe H, Matake H, et al. Anti-Saccharomyces cerevisiae antibodies in Japanese patients with inflammatory bowel disease: diagnostic accuracy and clinical value. J Gastroenterol. 2003;38:121–6. CrossRef
- Sugi K, Saitoh O, Matsuse R, Tabata K, Uchida K, Kojima K, et al. Antineutrophil cytoplasmic antibodies in Japanese patients with inflammatory bowel disease: prevalence and recognition of putative antigens. Am J Gastroenterol. 1999;94:1304–12. CrossRef
- Giaffer MH, Clark A, Holdsworth CD. Antibodies to Saccharomyces cerevisiae in patients with Crohn’s disease and their possible pathogenic importance. Gut. 1992;33:1071–5. CrossRef
- Standaert-Vitse A, Jouault T, Vandewalle P, Mille C, Seddik M, Sendid B, et al. Candida albicans is an immunogen for anti-Saccharomyces cerevisiae antibody markers of Crohn’s disease. Gastroenterology. 2006;130:1764–75. CrossRef
- Oshitani N, Hato F, Matsumoto T, Jinno Y, Sawa Y, Hara J, et al. Decreased anti-Saccharomyces cerevisiae antibody titer by mesalazine in patients with Crohn’s disease. J Gastroenterol Hepatol. 2000;15:1400–3. CrossRef
- Israeli E, Grotto I, Gilburd B, Balicer RD, Goldin E, Wiik A, et al. Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease. Gut. 2005;54:1232–6. CrossRef
- Cohavy O, Bruckner D, Gordon LK, Misra R, Wei B, Eggena ME, et al. Colonic bacteria express an ulcerative colitis pANCA-related protein epitope. Infect Immun. 2000;68:1542–8. CrossRef
- Fleshner PR, Vasiliauskas EA, Kam LY, Fleshner NE, Gaiennie J, Abreu-Martin MT, et al. High level perinuclear antineutrophil cytoplasmic antibody (pANCA) in ulcerative colitis patients before colectomy predicts the development of chronic pouchitis after ileal pouch-anal anastomosis. Gut. 2001;49:671–7. CrossRef
- Anti-high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1/HMGB2) antibodies and anti-Saccharomyces cerevisiae antibodies (ASCA): accuracy in differentially diagnosing UC and CD and correlation with inflammatory bowel disease phenotype
Journal of Gastroenterology
Volume 47, Issue 9 , pp 969-977
- Cover Date
- Print ISSN
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- Springer Japan
- Additional Links
- Anti-high mobility group box 1 and box 2 non-histone chromosomal proteins
- Anti-Saccharomyces cerevisiae antibodies
- Ulcerative colitis
- Crohn’s disease
- Industry Sectors
- Author Affiliations
- 1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
- 2. Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan
- 3. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan
- 4. Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan