Antineutrophil cytoplasmic antibodies (ANCA): current perspectives

  • C. G. M. Kallenberg


The idiopathic systemic vasculitides constitute a group of disorders characterized by more or less widespread inflammation of vessel walls generally without an underlying cause or an associated condition. The idiopathic vasculitides are traditionally grouped according to the size of the vessels involved and the histopathology of the inflammatory process. Such a classification is shown in Table 4.1. A recent modification of this scheme based on a more strict application of histopathological criteria with respect to the size of the vessels involved [1], is given in Table 4.2. The definitions and classification of the vasculitides demonstrate that histopathological findings are essential for making a diagnosis of a distinct vasculitic disorder. In clinical practice, however, pathognomonic histopathological findings are hard to obtain in most patients suspected of vasculitis, even in cases where multiple biopsies have been performed [2]. For this and other reasons, classification criteria have been designed by the American College of Rheumatologists (ACR) that are mainly based on clinical signs and symptoms [3]. These criteria can be used for the classification of patients who have al.ready have been proved to have vasculitis.


Primary Sclerosing Cholangitis Systemic Vasculitis Takayasu Arteritis Antineutrophil Cytoplasmic Antibody Crescentic Glomerulonephritis 
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  1. 1.
    Jennette, J.C., Falk, R.J., Andrassy, K. et al. (1994) Nomenclature of systemic vasculitides. Proposal of an International Consensus Conference. Arthritis Rheum., 37, 187–92.PubMedCrossRefGoogle Scholar
  2. 2.
    Cohen Tervaert, J.W., Limburg, P.C., Elema, J.D. et al. (1991) Detection of autoantibodies against myeloid lysosomal enzymes: a useful adjunct to classification of patients with biopsy-proven necrotizing arteritis. Am. J. Med., 91, 59–66.CrossRefGoogle Scholar
  3. 3.
    Leavitt, R.Y., Fauci, A.S., Bloch, D.A. et al. (1990) The American College of Rheumatology 1990 criteria for the classification of Wegener’s Granulomatosis. Arthritis Rheum., 33, 1101–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Davies, D.J., Moran, J.E., Niall, J.F. and Ryan, G.B. (1982) Segmental necrotizing glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? Br. Med. J., 285, 606.CrossRefGoogle Scholar
  5. 5.
    Van der Woude, F.J., Rasmussen, N., Lobatto, S. et al. (1985) Autoantibodies to neutrophils and monocytes: a new tool for diagnosis and a marker of disease activity in Wegener’s Granulomatosis. Lancet, ii, 425–9.CrossRefGoogle Scholar
  6. 6.
    Wiik, A. (1989) Delineation for a standard procedure for indirect immunofluorescence detection of ANCA. APMIS, 97 (Suppl. 6), S12–S13.Google Scholar
  7. 7.
    Cohen Tervaert, J.W., van der Woude, F.J., Fauci, A.S. et al. (1989) Association between active Wegener’s Granulomatosis and anticytoplasmic antibodies. Arch. Intern. Med., 149, 2461–5.CrossRefGoogle Scholar
  8. 8.
    Kallenberg, C.G.M., Mulder, A.H.L. and Cohen Tervaert, J.W. (1992) Antineutrophil cytoplasmic antibodies: a still growing class of autoantibodies in inflammatory disorders. Am. J. Med., 93, 675–82.PubMedCrossRefGoogle Scholar
  9. 9.
    Falk, R.J. and Jennette, J.C. (1988) Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N. Engl. J. Med., 318, 1651–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Peter, H.H., Metzger, D., Rump, A. and Röther, E. (1993) ANCA in diseases other than systemic vasculitis. Clin. Exp. Immunol., 91 (Suppl. 1), S12–S14.Google Scholar
  11. 11.
    Goldschmeding, F., Van der Schoot, C.E., Ten Bokkel Huinink, D. et al. (1989) Wegener’s Granulomatosis autoantibodies identify a novel diisopropylfluor-ophosphate-binding protein in the lysosomes of normal human neutrophils. J. Clin. Invest., 84, 1577–87.PubMedCrossRefGoogle Scholar
  12. 12.
    Niles, J.L., McCluskey, R.T., Ahmad, M.F. and Arnaout, M.A. (1989) Wegener’s Granulomatosis autoantigen is a novel serine proteinase. Blood, 74, 1888–93.PubMedGoogle Scholar
  13. 13.
    Lüdemann, J., Utecht, B. and Gross, W.I. (1990) Anti-neutrophil cytoplasm antibodies in Wegener’s Granulomatosis recognize an elastinolytic enzyme. J. Exp. Med., 171, 357–62.PubMedCrossRefGoogle Scholar
  14. 14.
    Goldschmeding, R., Cohen Tervaert, J.W., van der Schoot, C.E. et al. (1989) ANCA, anti-myeloperoxidase, and anti-elastase: three members of a novel class of autoantibodies against myeloid lysosomal enzymes. APMIS, 97 (S6), 48–9.Google Scholar
  15. 15.
    Cohen Tervaert, J.W., Mulder, A.H.L., Stegeman, C.A. et al. (1993) The occurrence of autoantibodies to human leukocyte elastase in Wegener’s Granulomatosis and other inflammatory disorders. Ann. Rheum. Dis., 52, 115–20.CrossRefGoogle Scholar
  16. 16.
    Charles, L.A., Falk, R.J. and Jennette, J.C. (1989) Reactivity of anti-neutrophil cytoplasmic autoantibodies with HL-60 cells. Clin. Immunol. Immunopathol., 53, 243–53.PubMedCrossRefGoogle Scholar
  17. 17.
    Mulder, A.H.L., Horst, G., van Leeuwen, M.A. et al. (1993) Anti-neutrophil cytoplasmic antibodies in rheumatoid arthritis: characterization and clinical correlations. Arthritis Rheum., 36, 1054–60.PubMedCrossRefGoogle Scholar
  18. 18.
    Coremans, E.M., Hagen, E.C., Daha, M.R. et al. (1992) Antilactoferrin antibodies in patients with rheumatoid arthritis are associated with vasculitis. Arthritis Rheum., 35, 1466–75.PubMedCrossRefGoogle Scholar
  19. 19.
    Mulder, A.H.L., Broekroelofs, J., Horst, G. et al. (1994) Antineutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease: characterization and clinical correlates. Clin. Exp. Immunol., 95, 490–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Coremans, I.E.M., Hagen, E.C., Daha, M.R. et al. (1993) Anti-lactoferrin antibodies in patients with Felty’s syndrome. Clin. Exp. Immunol., 93 (Suppl. 1), S33.Google Scholar
  21. 21.
    Lee, S.S., Lawton J.W.M. and Chan, C.E. (1992) Antilactoferrin antibody in systemic lupus erythematosus. Brit. J. Rheumatol., 31, 669–73.CrossRefGoogle Scholar
  22. 22.
    Peen, E., Aimer, S., Bodemar, G. et al. (1993) Anti-lactoferrin antibodies and other types of ANCA in ulcerative colitis, primary sclerosing cholangitis and Crohn’s disease. Gut, 34, 56–62.PubMedCrossRefGoogle Scholar
  23. 23.
    Sinico, R.A., Pozzi, C., Radice, A. et al. (1993) Clinical significance of anti-neutrophil cytoplasmic autoantibodies with specificity for lactoferrin in renal diseases. Am. J. Kidney Dis., 22, 253–60.PubMedGoogle Scholar
  24. 24.
    Halbwachs-Mecarelli, L.H., Nusbaum, L.H., Reumaux, D. et al. (1992) Anti-neutrophil cytoplasmic antibodies (ANCA) directed against Cathepsin G in ulcerative colitis, Crohn’s disease and primary sclerosing cholangitis. Clin. Exp. Immunol., 90, 79–84.PubMedCrossRefGoogle Scholar
  25. 25.
    Kaneko, K., Suzuki, Y., Yamashiro, Y. and Yabuta, S. (1993) Is p-ANCA in ulcerative colitis directed against β glucuronidase? Lancet, 341, 320.PubMedCrossRefGoogle Scholar
  26. 26.
    Nölle, B., Specks, U., Lüdemann, J. et al. (1989) Anticytoplasmic antibodies: their immunodiagnostic value in Wegener’s Granulomatosis. Ann. Intern. Med., 111, 28–40.PubMedCrossRefGoogle Scholar
  27. 27.
    Weber, M.F.A., Andrassy, K., Pullig, O. et al. (1992) Antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies in Goodpasture’s syndrome and in Wegener’s granulomatosis. J. Am. Soc. Nephrol., 2, 1227–34.PubMedGoogle Scholar
  28. 28.
    Cohen Tervaert, J.W., Goldschmeding, R., Elema, J.D. et al. (1990) Association of autoantibodies to myeloperoxidase with different forms of vasculitis. Arthritis Rheum., 33, 1264–72.CrossRefGoogle Scholar
  29. 29.
    Kallenberg, C.G.M. and Cohen Tervaert, J.W. (1992) Anti-neutrophilic cytoplasmic antibodies: new tools in the diagnosis and follow-up of necrotizing glomerulonephritis, in International Yearbook of Nephrology (eds V.E. Andreucci and L.G. Fine), pp. 313–36.Google Scholar
  30. 30.
    Cohen Tervaert, J.W., Goldschmeding, R., Elema, J.D. et al. (1990) Autoantibodies against myeloid lysosomal enzymes in crescentic glomerulonephritis. Kidney Int., 37, 799–806.CrossRefGoogle Scholar
  31. 31.
    Savage, C.O.S., Winearls, C.G., Evans, D.J. et al. (1985) Microscopic polyarteritis: presentation, pathology and prognosis. Q. J. Med., 56, 467–83.PubMedGoogle Scholar
  32. 32.
    Pudifin, D.J., Duursma, J., Gathiram, V. and Jackson, T.F.G.H. (1993) Serum from patients with invasive amoebiasis has anti-neutrophil cytoplasmic antibody activity. Clin. Exp. Immunol., 93 (Suppl. 1), S33.Google Scholar
  33. 33.
    Dolman, K.M., Gans, R.O.B., Vervaart, T.H.J., et al. (1993) Vasculitic disorders and anti-neutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy. Lancet, 342, 651–2.PubMedCrossRefGoogle Scholar
  34. 34.
    Egner, W. and Chapel, H.M. (1990) Titration of antibodies against neutrophil cytoplasmic antigens is useful in monitoring disease activity in systemic vasculitides. Clin. Exp. Immunol., 82, 244–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Cohen Tervaert, J.W., Huitema, M.G., Hené, R.J. et al. (1990) Prevention of relapses in Wegener’s granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre. Lancet, 336, 709–11.CrossRefGoogle Scholar
  36. 36.
    Kerr, G.R., Fleischer, T.H.A., Hallahan, C.W. et al. (1993) Limited prognostic value of changes in antineutrophil cytoplasmic antibody titer in patients with Wegener’s granulomatosis. Arthritis Rheum., 36, 365–71.PubMedCrossRefGoogle Scholar
  37. 37.
    Cohen Tervaert, J.W., Stegeman, C.A., Huitema, M.G. and Kallenberg, C.G.M. (1994) Comments on article by Kerr et al. Arthritis Rheum., 37, 596–7.CrossRefGoogle Scholar
  38. 38.
    Stegeman, C.A., Cohen Tervaert, J.W., Sluiter, W.J. et al. (1994) Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener’s Granulomatosis. Ann. Intern. Med., 120, 12–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Cohen Tervaert, J.W., Goldschmeding, R., Von dem Borne, A.E.G.K.R. and Kallenberg, C.G.M. (1991) Anti-myeloperoxidase antibodies in the Churg-Strauss syndrome. Thorax, 46, 70–1.CrossRefGoogle Scholar
  40. 40.
    Jayne, D.R.W., Marshall, P.D., Jones, S.J. and Lockwood, C.M. (1990) Autoantibodies to GBM and neutrophil cytoplasm in rapidly progressive glomerulonephritis. Kidney Int., 37, 965–70.PubMedCrossRefGoogle Scholar
  41. 41.
    Bosch, X., Mirapeix, E., Font, J. et al. (1991) Prognostic implication of antineutrophil cytoplasmic autoantibodies with myeloperoxidase specificity in anti-glomerular basement membrane disease. Clin. Nephrol., 36, 107–13.PubMedGoogle Scholar
  42. 42.
    Niles, J.L., Pan, G., Collins, A.B. et al. (1991) Antigen-specific radio-immu-noassay for anti-neutrophil cytoplasmic antibodies in the diagnosis of rapidly progressive glomerulonephritis. J. Am. Soc. Nephrol., 2, 27–36.PubMedGoogle Scholar
  43. 43.
    Gueirard, P., Delpech, A., Gilbert, D. et al. (1991) Anti-myeloperoxidase antibodies: immunological characteristics and clinical associations. J. Autoimm., 4, 517–27.CrossRefGoogle Scholar
  44. 44.
    Gallichio, M.C. and Savige, J.A. (1991) Detection of anti-myeloperoxidase and anti-elastase antibodies in vasculitis and infections. Clin. Exp. Immunol., 84, 232–7.CrossRefGoogle Scholar
  45. 45.
    Nässberger, L., Sjöholm, A.G., Jonsson, H. et al. (1990) Autoantibodies against neutrophil cytoplasm components in systemic lupus erythematosus and in hydralazine-induced lupus. Clin. Exp. Immunol., 81, 380–3.PubMedCrossRefGoogle Scholar
  46. 46.
    Mulder, A.H.L., Horst, G., Haagsma, E.B. et al. (1993) Prevalence and characterization of anti-neutrophil cytoplasmic antibodies in autoimmune liver diseases. Hepatology, 17, 411–17.PubMedCrossRefGoogle Scholar
  47. 47.
    Kallenberg, C.G.M., Cohen Tervaert, J.W. and Limburg, P.C. (1991) ELISA for the detection of antibodies against neutrophil cytoplasm antigens, in Techniques in diagnostic pathology, Vol. 2 (eds G.R. Bullock, D. van Velzen, M.J. Warhol and P. Herbrink), Academic Press, London, pp. 43–60.Google Scholar
  48. 48.
    Cohen Tervaert, J.W. and Kallenberg, C.G.M. (1993) Neurologic manifestations of systemic vasculitides, in Neurologic aspects of rheumatic diseases. Rheumatic Disease Clinics of North America (ed. K.B. Elkon), Vol. 19, WB Saunders, Philadelphia, pp. 913–40.Google Scholar
  49. 49.
    Kallenberg, C.G.M., Brouwer, E., Weening, J.J. and Cohen Tervaert, J.W. (1994) Anti-neutrophil cytoplasmic antibodies: current diagnostic and pathophysiological potential. Kidney Int., 46, 1–15.PubMedCrossRefGoogle Scholar
  50. 50.
    Falk, R.J., Terrell, R.S., Charles, L.A. and Jennette, J.C. (1990) Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc. Nat. Acad. Sci. USA, 87, 4115–9.CrossRefGoogle Scholar
  51. 51.
    Charles, L.A., Caldas, M.L.R., Falk, R.J. et al. (1991) Antibodies against granule proteins activate neutrophils in vitro. J. Leuk. Biol., 50, 539–46.Google Scholar
  52. 52.
    Mulder, A.H.L., Horst, G., Limburg, P.C. and Kallenberg, C.G.M. (1993) Activation of neutrophils by anti-neutrophil cytoplasmic antibodies is FcR-dependent. Clin. Exp. Immunol., 93 (Suppl. 1), S16.Google Scholar
  53. 53.
    Van de Wiel, A., Dolman, K.M., van der Meer-Gerritsen, C.H. et al. (1992) Interference of Wegener’s Granulomatosis autoantibodies with neutrophil proteinase 3 activity. Clin. Exp. Immunol., 90, 409–14.PubMedCrossRefGoogle Scholar
  54. 54.
    Dolman, K.M., Stegeman, C.A., van de Wiel, B.A. et al. (1993) Relevance of classic anti-neutrophil cytoplasmic autoantibody (c-ANCA)-mediated inhibition of proteinase 3-α1-antitrypsin complexation to disease activity in Wegener’s Granulomatosis. Clin. Exp. Immunol., 93, 405–10.PubMedCrossRefGoogle Scholar
  55. 55.
    Brouwer, E., Huitema, M.G., Klok, P.A. et al., (1993) Anti-myeloperoxidase associated proliferative glomerulonephritis: an animal model. J. Exp. Med., 177, 905–14.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media Dordrecht 1996

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  • C. G. M. Kallenberg

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