Abstract
pANCA (perinuclear antineutrophil cytoplasmic antibodies) occur at a high frequency in patients with ulcerative colitis. The purpose of this study was to investigate the frequency of pANCA in different mouse models of colitis and to determine whether there is any cross-reactivity of pANCA with bacterial antigens. Sera from 146 colitic mice and controls and from 30 patients with ulcerative colitis were tested for the presence of pANCA by indirect immunofluorescence with or without prior absorption with homogenized murine cecal bacteria. pANCA was found in 24 of 36 IL10–/– mice. In contrast to the human pANCA, both nuclear and perinuclear staining was found. Absorption of either human or mouse pANCA-positive sera with enteric bacterial antigens greatly reduced or abolished the specific perinuclear staining of pANCA. We conclude that pANCA occurs not only in humans but also in IL10–/– mice with colitis and likely represents a cross-reactivity with enteric bacterial antigens.
Similar content being viewed by others
REFERENCES
Broberger O, Perlmann P: Autoantibodies in human ulcerative colitis. J Exp Med 110:657–674, 1959
Harrison WJ: Autoantibodies against intestinal and gastric mucous cells in ulcerative colitis. Lancet 1:1346–1350, 1965
Perlmann P, Hammarstrom S, Lagercrantz R, Gustafson BE: Antigen from colon of germfree rats and antibodies in human ulcerative colitis. Ann NY Acad Sci 124:377–384, 1965
Marcussen H: Fluorescent anti-colonic and E. coli antibodies in ulcerative colitis. Scand J Gastroenterol 13:277–281, 1978
Noelle B, Specks U, Luedemann J, Rohrbach MS, DeRemee RA, Gross WL: Anticytoplasmic autoantibodies: Their immundiagnostic value in Wegener granulomatosis. Ann Intern Med 111:28–40, 1989
Seibold F, Weber P, Klein R, Berg PA, Wiedmann KH: Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis. Gut 33:657–662, 1992
Saxon A, Shanahan F, Landers C, Ganz T, Targan S: A distinct subset of antineutrophil cytoplasmic antibodies is associated with inflammatory bowel disease. J Allergy Clin Immunol 86:202–210, 1990
Shanahan F, Duerr R, Rotter JI, Yang H, Sutherland LR, McElree C, Landers CJ, Targan SR: Neutrophil antibodies in ulcerative colitis: Familial aggregation and genetic heterogeneity. Gastroenterology 103:456–461, 1992
Seibold F, Slametschka D, Gregor M, Weber P: Neutrophil autoantibodies: A genetic marker in primary sclerosing cholangitis and ulcerative colitis. Gastroenterology 107:532–536, 1994
Lee CW, Lennard-Jones JE, Cambridge G: Antineutrophil antibodies in familial inflammatory bowel disease. Gastroenterology 108:428–433, 1995
Hollander GA, Simpson SJ, Mizoguchi E, Nichogiannopoulou A, She J, Gutierrez-Ramos JC, Bhan AK, Burakoff SJ, Wang B, Terhorst C: Severe colitis in mice with aberrant thymic selection. Immunity 3:27–38, 1995
Hammer RE, Maika SD, Richardson RA, Tang YP, Taurog JD: Spontaneous inflammatory disease in transgenic rats expressing HLA B27 and human β2m: An animal model of HLA B27 associated human disorders. Cell 63:1099–1112, 1990
Sadlack B, Merz H, Schorle H, Schimpl A, Feller AC, Horak I: Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 75:253–261, 1993
Kühn R, Köhler J, Rennick D, Rajewsk K, Müller W: Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75:263–274, 1993
Powrie F, Leach MW, Mauze S, Menon S, Caddle LB, Coffman RL: Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity 1:553–562, 1994
Sundberg JP, Elson CO, Bedigian H, Birkenmeier EH: Spontaneous, heritable colitis in a new substrain of C3H/HeJ. Gastroenterology 107:1726–1735, 1994
Targan SR, Landers CJ, King NW, Podolsky DJ, Shanahan F: Ulcerative colitis-linked antineutrophil cytoplasmic antibody in the cotton-top tamarin model of colitis. Gastroenterology 102:1493–1498, 1992
Duerr RH, Targan SR, Landers CJ, LaRusso NF, Lindsay KL, Wiesner RH, Shanahan F: Neutrophil cytoplasmic antibodies: A link between primary sclerosing cholangitis and ulcerative colitis. Gastroenterology 100:1385–1391, 1991
Rump AJ, Schoelmerich J, Gross V, et al.: A new type of perinuclear anti-neutrophil cytoplasmic antibody (pANCA) in active ulcerative colitis but not in Crohn's disease. Immunobiology 181:406–413, 1990
Peen E, Almer S, Bodemar G, Ryden BO, Sjölin C, Tejle K, Shogh T: Anti-lactoferrin antibodies and other types of ANCA in ulcerative colitis, primary sclerosing cholangitis and Crohn's disease. Gut 34:56–62, 1993
Broekroelofs J, Mulder AHL, Nelis GF, Westerveld BD, Cohen Tervaert JW, Kallenberg CGM: Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with inflammatory bowel disease (IBD). Dig Dis Sci 39:545–549, 1994
Seibold F, Weber P, Schoening A, Moerk H, Goppel S, Scheurlen M: Neutrophil antibodies (pANCA) in chronic liver disease and inflammatory bowel disease: Do they react with different antigens? Eur J Gastroenterol 8:1095–1100, 1996
Halbwachs-Mecarelli L, Nusbaum P, Noel LH, Reumaux D, Erlinger S, Grunfeld JP, Lesavre P: Antineutrophil cytoplasmic antibodies (ANCA) directed against cathepsin G in ulcerative colitis, Crohn's disease and primary sclerosing cholangitis. Clin Exp Immunol 90:79–84, 1992
Mulder AHL, Horst G, Haagsma EB, Limburg PC, Kleibeuker JH, Kallenberg CGM: Prevalence and characterization of neutrophil cytoplasmic antibodies in autoimmune liver disease. Hepatology 17:411–417, 1993
Winfield J, Jarjour W: Do stress proteins play a role in arthritis and autoimmunity? Immunol Rev 121:193–220, 1991
Brandwein SL, McCabe RP, Cong Y, Waites KB, Ridwan BU, Dean PA, Obkusa T, Birkenmeier EH, Sundberg JP, Elson CO: Spontaneously colitic C3H/HeJBir mice demonstrate selective antibody reactivity to antigens of the enteric bacterial flora. J Immunol 159:44–52, 1997
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Seibold, F., Brandwein, S., Simpson, S. et al. pANCA Represents a Cross-Reactivity to Enteric Bacterial Antigens. J Clin Immunol 18, 153–160 (1998). https://doi.org/10.1023/A:1023203118100
Issue Date:
DOI: https://doi.org/10.1023/A:1023203118100