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. 1995 Oct;147(4):979–987.

Nuclear localization of the antigen detected by ulcerative colitis-associated perinuclear antineutrophil cytoplasmic antibodies.

P Billing 1, S Tahir 1, B Calfin 1, G Gagne 1, L Cobb 1, S Targan 1, A Vidrich 1
PMCID: PMC1871001  PMID: 7573373

Abstract

Antineutrophil cytoplasmic antibodies (ANCAs) identified in the serum of 50 to 80% of ulcerative colitis (UC) patients yield a perinuclear staining pattern (pANCA) with alcohol-fixed neutrophils. The ANCAs of UC are distinguishable from those described for Wegener's granulomatosis and other vasculitidies. These various non-UC ANCAs recognize neutrophil granule constituents, but the antigenic moiety specific for the UC pANCA remains unknown. Although the perinuclear nature of some ANCA reactions is an artifact of the alcohol fixation of neutrophils, which causes cytoplasmic granules to redistribute around the nucleus, the UC pANCA reaction has been found not to be similarly affected. We postulated a nuclear localization for the UC-associated pANCA antigen and used both confocal laser microscopy and immunoelectron microscopy to examine the neutrophil reaction of UC-associated pANCA-containing sera. Confocal microscopy revealed a nuclear reaction for 88% (22/25) of the sera with 72% (18/25) showing the reaction localizing to the inner side of the nuclear (membrane) periphery. Immunoelectron microscopy showed that the UC-associated pANCA reaction localized primarily over chromatin concentrated toward the nuclear periphery, although the sera did not recognize double-stranded DNA. These results confirm the nuclear localization of the UC-associated pANCA antigen.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Broekroelofs J., Mulder A. H., Nelis G. F., Westerveld B. D., Tervaert J. W., Kallenberg C. G. Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with inflammatory bowel disease (IBD). Relation to disease pattern and disease activity. Dig Dis Sci. 1994 Mar;39(3):545–549. doi: 10.1007/BF02088340. [DOI] [PubMed] [Google Scholar]
  2. Cambridge G., Rampton D. S., Stevens T. R., McCarthy D. A., Kamm M., Leaker B. Anti-neutrophil antibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut. 1992 May;33(5):668–674. doi: 10.1136/gut.33.5.668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Davies D. J., Moran J. E., Niall J. F., Ryan G. B. Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? 1982 Aug 28-Sep 4Br Med J (Clin Res Ed) 285(6342):606–606. doi: 10.1136/bmj.285.6342.606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Deusch K., Oberstadt K., Schaedel W., Weber M., Classen M. p-ANCA as a diagnostic marker in ulcerative colitis. Adv Exp Med Biol. 1993;336:527–531. doi: 10.1007/978-1-4757-9182-2_96. [DOI] [PubMed] [Google Scholar]
  5. Duerr R. H., Targan S. R., Landers C. J., Sutherland L. R., Shanahan F. Anti-neutrophil cytoplasmic antibodies in ulcerative colitis. Comparison with other colitides/diarrheal illnesses. Gastroenterology. 1991 Jun;100(6):1590–1596. doi: 10.1016/0016-5085(91)90657-7. [DOI] [PubMed] [Google Scholar]
  6. Falk R. J., Hogan S. L., Wilkman A. S., Terrell R. S., Lauritzen S., Charles L. A., Jennette J. C. Myeloperoxidase specific anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA). Neth J Med. 1990 Apr;36(3-4):121–125. [PubMed] [Google Scholar]
  7. Falk R. J., Jennette J. C. Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med. 1988 Jun 23;318(25):1651–1657. doi: 10.1056/NEJM198806233182504. [DOI] [PubMed] [Google Scholar]
  8. Falk R. J., Jennette J. C. Wegener's granulomatosis, systemic vasculitis, and antineutrophil cytoplasmic autoantibodies. Annu Rev Med. 1991;42:459–469. doi: 10.1146/annurev.me.42.020191.002331. [DOI] [PubMed] [Google Scholar]
  9. Goldschmeding R., van der Schoot C. E., ten Bokkel Huinink D., Hack C. E., van den Ende M. E., Kallenberg C. G., von dem Borne A. E. Wegener's granulomatosis autoantibodies identify a novel diisopropylfluorophosphate-binding protein in the lysosomes of normal human neutrophils. J Clin Invest. 1989 Nov;84(5):1577–1587. doi: 10.1172/JCI114335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gross W. L., Schmitt W. H., Csernok E. ANCA and associated diseases: immunodiagnostic and pathogenetic aspects. Clin Exp Immunol. 1993 Jan;91(1):1–12. doi: 10.1111/j.1365-2249.1993.tb03345.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hardarson S., Labrecque D. R., Mitros F. A., Neil G. A., Goeken J. A. Antineutrophil cytoplasmic antibody in inflammatory bowel and hepatobiliary diseases. High prevalence in ulcerative colitis, primary sclerosing cholangitis, and autoimmune hepatitis. Am J Clin Pathol. 1993 Mar;99(3):277–281. doi: 10.1093/ajcp/99.3.277. [DOI] [PubMed] [Google Scholar]
  12. Hardin J. A., Thomas J. O. Antibodies to histones in systemic lupus erythematosus: localization of prominent autoantigens on histones H1 and H2B. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7410–7414. doi: 10.1073/pnas.80.24.7410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jennette J. C., Charles L. A., Falk R. J. Antineutrophil cytoplasmic autoantibodies: disease associations, molecular biology, and pathophysiology. Int Rev Exp Pathol. 1991;32:193–221. doi: 10.1016/b978-0-12-364932-4.50009-5. [DOI] [PubMed] [Google Scholar]
  14. Kallenberg C. G., Tervaert J. W., van der Woude F. J., Goldschmeding R., von dem Borne A. E., Weening J. J. Autoimmunity to lysosomal enzymes: new clues to vasculitis and glomerulonephritis? Immunol Today. 1991 Feb;12(2):61–64. doi: 10.1016/0167-5699(91)90159-q. [DOI] [PubMed] [Google Scholar]
  15. Lesavre P., Noël L. H., Gayno S., Nusbaum P., Reumaux D., Erlinger S., Grünfeld J. P., Halbwachs-Mecarelli L. Atypical autoantigen targets of perinuclear antineutrophil cytoplasm antibodies (P-ANCA): specificity and clinical associations. J Autoimmun. 1993 Apr;6(2):185–195. doi: 10.1006/jaut.1993.1016. [DOI] [PubMed] [Google Scholar]
  16. Mulder A. H., Broekroelofs J., Horst G., Limburg P. C., Nelis G. F., Kallenberg C. G. Anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease: characterization and clinical correlates. Clin Exp Immunol. 1994 Mar;95(3):490–497. doi: 10.1111/j.1365-2249.1994.tb07024.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nölle B., Specks U., Lüdemann J., Rohrbach M. S., DeRemee R. A., Gross W. L. Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener granulomatosis. Ann Intern Med. 1989 Jul 1;111(1):28–40. doi: 10.7326/0003-4819-111-1-28. [DOI] [PubMed] [Google Scholar]
  18. Oudkerk Pool M., Ellerbroek P. M., Ridwan B. U., Goldschmeding R., von Blomberg B. M., Peña A. S., Dolman K. M., Bril H., Dekker W., Nauta J. J. Serum antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease are mainly associated with ulcerative colitis. A correlation study between perinuclear antineutrophil cytoplasmic autoantibodies and clinical parameters, medical, and surgical treatment. Gut. 1993 Jan;34(1):46–50. doi: 10.1136/gut.34.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pryzwansky K. B., Martin L. E., Spitznagel J. K. Immunocytochemical localization of myeloperoxidase, lactoferrin, lysozyme and neutral proteases in human monocytes and neutrophilic granulocytes. J Reticuloendothel Soc. 1978 Sep;24(3):295–310. [PubMed] [Google Scholar]
  20. Rump J. A., Schölmerich J., Gross V., Roth M., Helfesrieder R., Rautmann A., Lüdemann J., Gross W. L., Peter H. H. A new type of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in active ulcerative colitis but not in Crohn's disease. Immunobiology. 1990 Nov;181(4-5):406–413. doi: 10.1016/S0171-2985(11)80509-7. [DOI] [PubMed] [Google Scholar]
  21. 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. 1990 Aug;86(2):202–210. doi: 10.1016/s0091-6749(05)80067-3. [DOI] [PubMed] [Google Scholar]
  22. Seibold F., Slametschka D., Gregor M., Weber P. Neutrophil autoantibodies: a genetic marker in primary sclerosing cholangitis and ulcerative colitis. Gastroenterology. 1994 Aug;107(2):532–536. doi: 10.1016/0016-5085(94)90181-3. [DOI] [PubMed] [Google Scholar]
  23. Seibold F., Weber P., Klein R., Berg P. A., Wiedmann K. H. Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis. Gut. 1992 May;33(5):657–662. doi: 10.1136/gut.33.5.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Shanahan F., Duerr R. H., Rotter J. I., Yang H., Sutherland L. R., McElree C., Landers C. J., Targan S. R. Neutrophil autoantibodies in ulcerative colitis: familial aggregation and genetic heterogeneity. Gastroenterology. 1992 Aug;103(2):456–461. doi: 10.1016/0016-5085(92)90834-l. [DOI] [PubMed] [Google Scholar]
  25. Shanahan F., Landers C., Duerr R., Targan S. R. Neutrophil autoantibodies as disease markers for ulcerative colitis. Immunol Res. 1991;10(3-4):479–484. doi: 10.1007/BF02919745. [DOI] [PubMed] [Google Scholar]
  26. Sung J. Y., Chan F. K., Lawton J., Leung J. C., Liew C. T., Leung N. W., Hsu R., Lai K. N. Anti-neutrophil cytoplasmic antibodies (ANCA) and inflammatory bowel diseases in Chinese. Dig Dis Sci. 1994 Apr;39(4):886–892. doi: 10.1007/BF02087438. [DOI] [PubMed] [Google Scholar]
  27. Tervaert J. W., Mulder L., Stegeman C., Elema J., Huitema M., The H., Kallenberg C. Occurrence of autoantibodies to human leucocyte elastase in Wegener's granulomatosis and other inflammatory disorders. Ann Rheum Dis. 1993 Feb;52(2):115–120. doi: 10.1136/ard.52.2.115. [DOI] [PMC free article] [PubMed] [Google Scholar]

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