Perspectives in Clinical Nephrology

Kidney International (1994) 46, 1–15; doi:10.1038/ki.1994.239

Anti-neutrophil cytoplasmic antibodies: Current diagnostic and pathophysiological potential

Editor's Note:

The scope of nephrology is, happily, continually expanding. Kidney International is acutely aware of its responsibility, as the official journal of the International Society of Nephrology, to serve the needs of the entire spectrum of renal clinicians and investigators.

For some years, the invited editorials appearing at the beginning of each month's issue of Kidney International, together with Nephrology Forum, have served the needs of our constituencies. But clinical nephrology has grown explosively. Moreover, the translation of laboratory information into clinically useful arguments is becoming increasingly short.

For that reason, beginning with this issue of Kidney International, we introduce a new series entitled Perspectives in Clinical Nephrology. Both PCN and Nephrology Forum will be directed primarily toward clinicians and/or clinical investigators whose major focus of inquiry is the patient. Like Nephrology Forum, PCN will attempt to translate, as rapidly as possible, advances made in the laboratory into constructs that help analyze the physiology and pathophysiology of disease. In turn, this construct will allow us to orient the Editorial Reviews, to an increasing degree, toward issues focused more on laboratory inquiry.

The Editors hope that this new series will, to an increasing degree, serve the needs of all of the readership of Kidney International.

T.E. Andreoli

For the Editors

Cees G M Kallenberg, Elisabeth Brouwer, Jan J Weening and Jan W Cohen Tervaert

University Hospital, Groningen, and Academic Medical Center, Amsterdam, The Netherlands

Correspondence: C G M Kallenberg MD PhD, Department of Clinical Immunology, University Hospital, Oostersingel 59, 9713 EZ Groningen, The Netherlands.

Received 27 October 1993; Revised 7 February 1994; Accepted 7 February 1994.

Top

Abstract

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome characterized by rapid deterioration of renal function occurring within days or weeks together with signs of glomerulonephritis, that is, proteinuria and hematuria with cellular casts. The syndrome is, in many cases, histopathologically manifested as fibrinoid necrosis of the capillary wall with extracapillary proliferation and crescent formation [1]. This so-called necrotizing crescentic glomerulonephritis (NCGN) is seen in 5 to 15% of renal biopsies in most series [1–3]. Although it is infrequent, the importance of the condition is illustrated by the fact that most cases of NCGN, if left untreated, develop renal failure within days or weeks [1]. Based on immunohistopathology NCGN can be subdivided into three distinct categories. The first one, occurring in 2 to 20% of the cases and characterized by linear staining of the glomerular capillary wall for immunoglobulin and complement, has classically been described as anti-glomerular basement membrane (GBM) disease. It is associated with autoantibodies to structural antigens of the GBM, in particular to the first globular noncollagen domain of collagen type IV [4]. The antibodies are considered of pathogenetic significance. The second category, comprising 15 to 50% of cases, is characterized by granular deposits of immunoglobulin and complement suggesting that immune complexes are pathogenetically involved. This type occurs in conjunction with systemic autoimmune diseases such as lupus erythematosus, in cases of post-infectious glomerulonephritis, IgA nephropathy or Henoch-Schönlein purpura, or as an idiopathic variety. The third group of NCGN, occurring in 40 to 80%, demonstrates only a few or no immune deposits and is designated as pauci-immune NCGN [1–3, 5, 6]. Pauci-immune NCGN occurs as part of Wegener's granulomatosis (WG) or related conditions, or without systemic vasculitis (idiopathic NCGN). The pathophysiology of this pauci-immune type of NCGN has not been elucidated. Within the last decade, however, it has been recognized that the condition is associated with autoantibodies to cytoplasmic components of neutrophils (anti-neutrophil cytoplasmic antibodies or ANCA).

ANCA were first described in 1982 by Davies et al in a few patients with segmental necrotizing glomerulonephritis [7]. Only in 1985 did it become apparent that ANCA are a sensitive and specific marker for Wegener's granulomatosis (WG) [8]. Later on, ANCA were described in patients with microscopic polyarteritis [9]. Falk and Jennette, in 1988, showed that ANCA are also associated with the idiopathic form of pauci-immune NCGN [10]. These data have now been confirmed by many groups and support the view that ANCA-associated glomerulonephritis and vasculitis is, indeed, a distinct disease category. A number of studies, in addition, have suggested that ANCA are involved in the pathophysiology of the aforementioned disorders. As ANCA, however, have recently also been detected in a wide range of inflammatory and infectious conditions, a critical reappraisal of the diagnostic significance of ANCA-testing seems justified.

In this review we will evaluate the current state of ANCA-testing as well as elaborate on the pathophysiological role of the autoantibodies in necrotizing glomerulonephritis and vasculitis. Data presented recently at the Fifth International Workshop on ANCA, held in Cambridge, United Kingdom, will be included [11]. As such, it adds to previous reviews on ANCA that were published following the Second [12], Third [13], and Fourth [14] Workshops on ANCA.

Top

References

  1. Couser WG: Rapidly progressive glomerulonephritis: Classification, pathogenetic mechanisms, and therapy. Am J Kidney Dis 11:449–464, 1988 | PubMed | ISI | ChemPort |
  2. Jennette JC, Falk RJ: Diagnosis and management of glomerulonephritis and vasculitis presenting as acute renal failure. Med Clin North Am 74:893–908, 1990 | PubMed | ISI | ChemPort |
  3. Cohen Tervaert JW, Goldschmeding R, Elema JD, Van Der Giessen M, Huitema MG, Van Der Hem GK, The TH, Von Dem Borne AEGKR, Kallenberg CGM: Autoantibodies against myeloid lysosomal enzymes in crescentic glomerulonephritis. Kidney Int 37:799–806, 1990 | Article | PubMed |
  4. Wieslander J, Barr JF, Butkowski RJ, Edwards SJ, Bygren P, Heinegard D, Hudson BG: Goodpasture antigen of the glomerular basement membrane: Localization to noncollagenous regions of type IV collagen. Proc Natl Acad Sci USA 81:3838–3840, 1984 | PubMed | ChemPort |
  5. Stilmant MM, Bolton WK, Sturgill BC, Schmitt GW, Couser WG: Crescentic glomerulonephritis without immune deposits: Clinicopathologic features. Kidney Int 15:184–195, 1979 | PubMed |
  6. Jennette JC, Wilkman AS, Falk RJ: Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis. Am J Pathol 135:921–930, 1989 | PubMed | ISI | ChemPort |
  7. Davies DJ, Moran JE, Niall JF, Ryan GB: Segmental necrotizing glomerulonephritis with antineutrophil antibody: Possible arbovirus aetiology? Br Med J 285:606, 1982 | ISI | ChemPort |
  8. Van Der Woude FJ, Rasmussen N, Lobatto S, Wiik A, Permin H, Van Es LA, Van Der Giessen M, Van Der Hem GK, The TH: Autoantibodies to neutrophils and monocytes: A new tool for diagnosis and a marker of disease activity in Wegener's Granulomatosis. Lancet ii:425–429, 1985
  9. Savage COS, Winearls CG, Jones SJ, Marshall PD, Lockwood CM: Prospective study of radioimmunoassay for antibodies against neutrophil cytoplasm in diagnosis of systemic vasculitis. Lancet 8:1389–1393, 1987
  10. Falk RJ, Jennette JC: Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med 318:1651–1657, 1988 | PubMed | ISI | ChemPort |
  11. Mathieson PW (editor): Proceedings of the 5th International ANCA Workshop. Clin Exp Immunol 93(Suppl 1):S1–S47, 1993
  12. Van Der Woude FJ, Daha MR, Van Es LA: The current status of neutrophil cytoplasmic antibodies. Clin Exp Immunol 78:143–148, 1989
  13. Jennette JC, Falk RJ: Antineutrophil cytoplasmic autoantibodies and associated diseases: A review. Am J Kidney Dis 15:517–529, 1990
  14. Hagen EC, Ballieux BE, Van Es LA, Daha MR, Van Der Woude FJ: Antineutrophil cytoplasmic autoantibodies: A review of the antigens involved, the assays and the clinical and possible pathogenetic consequences. Blood 81:1996–2002, 1993 | PubMed | ISI |
  15. Wiik A: Delineation for a standard procedure for indirect immunofluorescence detection of ANCA. APMIS 97(Suppl 6):S12–S13, 1989
  16. Cohen Tervaert JW, Van Der Woude FJ, Fauci AS, Ambrus JL, Velosa J, Keane WF, Meijer S, Van Der Giessen M, The TH, Van Der Hem GK, Kallenberg CGM: Association between active Wegener's Granulomatosis and anticytoplasmic antibodies. Arch Intern Med 149:2461–2465, 1989 | Article | PubMed |
  17. Kallenberg CGM, Mulder AHL, Cohen Tervaert JW: Antineutrophil cytoplasmic antibodies: A still growing class of autoantibodies in inflammatory disorders. Am J Med 93:675–682, 1992 | Article | PubMed | ISI | ChemPort |
  18. Peter HH, Metzger D, Rump A, Röther E: ANCA in diseases other than systemic vasculitis. Clin Exp Immunol 91 (Suppl 1):S12–S14, 1993
  19. Faber V, Elling P, Norup G, Mansa B, Nissen NI: An antinuclear factor specific for leucocytes. Lancet ii:344–345, 1964
  20. Wiik A: Granulocyte-specific antinuclear antibodies. Allergy 35:263–289, 1980 | PubMed |
  21. Charles LA, Falk RJ, Jennette JC: Reactivity of anti-neutrophil cytoplasmic autoantibodies with HL-60 cells. Clin Immunol Immunopathol 53:243–253, 1989
  22. Pryzwansky MB, Martin LE, Spitznagel JK: Immunocytochemical localization of myeloperoxidase, lactoferrin, lysozyme, and neutral proteases in human monocytes and neutrophilic granulocytes. J Reticuloendothel Soc 24:295–310, 1978 | PubMed | ISI |
  23. Mulder AHL, Horst G, Van Leeuwen MA, Limburg PC, Kallenberg CGM: Antineutrophil cytoplasmic antibodies in rheumatoid arthritis: Characterization and clinical correlations. Arthritis Rheum 36:1054–1060, 1993 | PubMed | ISI | ChemPort |
  24. Hagen EC, Andrassy K, Csernok E, Daha MR, Gaskin G, Gross WL, Lesavre PH, Lüdemann J, Pusey CD, Rasmussen N, Savage COS, Sinico A, Wiik A, Van Der Woude FJ: The value of indirect immunofluorescence and solid phase techniques for ANCA detection. J Immunol Meth 159:1–16, 1993
  25. Goldschmeding R, Van Der Schoot CE, Ten Bokkel Huinink D, Hack CE, Van Den Ende ME, Kallenberg CGM, Von Dem Borne AEGKR: Wegener's Granulomatosis autoantibodies identify a novel diisopropylfluorophosphate-binding protein in the lysosomes of normal human neutrophils. J Clin Invest 84:1577–1587, 1989 | PubMed | ISI | ChemPort |
  26. Niles JL, McCluskey RT, Ahmad MF, Arnaout MA: Wegener's Granulomatosis autoantigen is a novel serine proteinase. Blood 74:1888–1893, 1989 | PubMed | ISI | ChemPort |
  27. Lüdemann J, Utecht B, Gross WL: Anti-neutrophil cytoplasm antibodies in Wegener's Granulomatosis recognize an elastinolytic enzyme. J Exp Med 171:357–362, 1990 | PubMed |
  28. Campanelli D, Melchior M, Fu Y, Nakata N, Shuman H, Nathan C, Gabay JE: Cloning of cDNA for proteinase 3: A serine protease, antibiotic, and autoantigen from human neutrophils. J Exp Med 172:1709–1715, 1990 | Article | PubMed | ISI | ChemPort |
  29. Campanelli D, Detmers PA, Nathan CF, Gabay JE: Azurocidin and a homologous serine protease from neutrophils. Differential antimicrobial and proteolytic properties. J Clin Invest 85:904–915, 1990 | PubMed | ISI | ChemPort |
  30. Bories D, Raynal MC, Solomon DH, Darzynkiewicz Z, Cayre Y: Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells. Cell 59:959–968, 1989 | Article | PubMed | ISI | ChemPort |
  31. Kam CM, Kerrigan JE, Dolman KM, Goldschmeding R, Von Dem Borne AEGKR, Powers JC: Substrate and inhibitor studies on Proteinase 3. FEBS Lett 297:119–123, 1992 | Article | PubMed | ISI | ChemPort |
  32. Dolman KM, Van De Wiel BA, Kam CM, Abbink JJ, Hack CE, Sonnenberg A, Powers JC, Von Dem Borne AEGKR, Goldschmeding R: Determination of proteinase 3/alpha1-antitrypsin complexes in inflammatory fluids. FEBS Lett 314:117–121, 1992
  33. Dalpé G, Boire G, Ménard HA: The conformational determinants recognized by Wegener's c-ANCA are situated at or near the catalytic domain of myeloblastin. Clin Exp Immunol 93 (Suppl 1):S21, 1993
  34. Bini P, Gabay JE, Teitel A, Melchior M, Zhou JL, Elkon KB: Antineutrophil cytoplasmic autoantibodies in Wegener's Granulomatosis recognize conformational epitope(s) on proteinase 3. J Immunol 149:1409–1415, 1992 | PubMed | ISI | ChemPort |
  35. Van De Wiel A, Dolman KM, Van Der Meer-Gerritsen CH, Hack CE, Von Dem Borne AEGKR, Goldschmeding R: Interference of Wegener's Granulomatosis autoantibodies with neutrophil proteinase 3 activity. Clin Exp Immunol 90:409–414, 1992
  36. Goldschmeding R, Van Der Schoot CE, Calafat J, Wyermans PW, Von Dem Borne AEGKR: Differential expression of proteinase 3, leukocyte elastase and myeloperoxidase in myeloid leukaemia and cell line cells, in Target Antigens of Antineutrophil Cytoplasmic Antibodies (Thesis), edited by Goldschmeding R, Amsterdam, The Netherlands, 1992, pp 75–84
  37. Charles LA, Falk RJ, Jennette JC: Reactivity of neutrophil cytoplasmic autoantibodies with mononuclear phagocytes. J Leuk Biol 51:65–68, 1992
  38. Calafat J, Goldschmeding R, Ringeling PL, Janssen H, Van Der Schoot CE: In situ localization by double-labeling immunoelectron microscopy of anti-neutrophil cytoplasmic autoantibodies in neutrophils and monocytes. Blood 75:242–250, 1990
  39. Charles LA, Caldas MLR, Falk RJ, Terrell RS, Jennette JC: Antibodies against granule proteins activate neutrophils in vitro. J Leuk Biol 50:539–546, 1991 | ISI | ChemPort |
  40. Csernok E, Schmitt WH, Bainton D, Gross WL: Translocation of Pr-3 on the cell surface of neutrophils: Association with disease activity in Wegener's granulomatosis. (abstract) Arthritis Rheum 34:S79, 1991
  41. Mayet WJ, Hermann E, Csernok E, Knuth A, Poralla T, Gross WL, Meyer Zum Büschenfelde KB: A human renal cancer line as a new antigen source for the detection of antibodies to cytoplasmic and nuclear antigens in sera of patients with Wegener's Granulomatosis. J Immunol Meth 143:57–64, 1991
  42. Mayet WJ, Csernok E, Szymkowiak C, Gross WL, Meyer Zum Büschenfelde KH: Human endothelial cells express proteinase 3, the target antigen of anti-cytoplasmic antibodies in Wegener's Granulomatosis. Blood 82:1221–1229, 1993 | PubMed | ISI | ChemPort |
  43. Kao RC, Wehner NG, Skubitz KM, Gray BH, Hoidal JR: Proteinase 3: A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters. J Clin Invest 82:1963–1973, 1988 | PubMed | ISI | ChemPort |
  44. Lüdemann J, Utecht B, Gross WL: Detection and quantitation of anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis by ELISA using affinity-purified antigen. J Immunol Meth 114:167–174, 1988
  45. Gaskin G, Turner AN, Ryan JJ, Rees AJ, Pusey CD: Purification of proteinase 3 and its reactivity with sera from patients with Wegener's granulomatosis and microscopic polyarteritis. (abstract) J Am Soc Nephrol 2:595, 1991
  46. Goldschmeding R, Cohen Tervaert JW, Van Der Schoot CE, Van Der Veen C, Kallenberg CGM, Von Dem Borne AEGKR: ANCA, anti-myeloperoxidase, and anti-elastase: Three members of a novel class of autoantibodies against myeloid lysosomal enzymes. APMIS 97(S6):48–49, 1989
  47. Falk RJ, Jennette JC: Immunofluorescence and ELISA determination of ANCA with description of a sub-class with anti-myeloperoxidase activity. APMIS 97(S6):45, 1989
  48. Cohen Tervaert JW, Goldschmeding R, Elema JD, Limburg PC, Van Der Giessen M, Huitema MG, Koolen MI, Hené RJ, The TH, Van Der Hem GK, Von Dem Borne AEGKR, Kallenberg CGM: Association of autoantibodies to myeloperoxidase with different forms of vasculitis. Arthritis Rheum 33:1264–1272, 1990 | PubMed |
  49. Segelmark M, Baslund B, Wieslander J: Some patients with c-ANCA pattern have antibodies to myeloperoxidase and not to proteinase 3. Clin Exp Immunol 93 (Suppl 1):S32, 1993
  50. Weiss SJ: Tissue destruction by neutrophils. N Engl J Med 320:365–376, 1989 | PubMed | ISI | ChemPort |
  51. Roberts DE, Peebles C, Curd JG, Tan EM, Rubin RL: Autoantibodies to native myeloperoxidase in patients with pulmonary hemorrhage and acute renal failure. J Clin Immunol 11:389–397, 1991 | Article | PubMed | ISI | ChemPort |
  52. Falk RJ, Becker M, Terrell R, Jennette JC: Anti-myeloperoxidase autoantibodies react with native but not denatured myeloperoxidase. Clin Exp Immunol 89:274–278, 1992 | PubMed | ISI | ChemPort |
  53. Esnault VLM, Mathieson PW, Thiru S, Oliveira DBG, Lockwood CM: Autoantibodies to myeloperoxidase in Brown Norway rats treated with mercuric chloride. Lab Invest 67:114–120, 1992 | PubMed |
  54. Cambridge G, Hall TJ, Leaker B: Heterogeneity of antibodies to myeloperoxidase in sera from patients with vasculitis. (abstract) J Am Soc Nephrol 2:590, 1991
  55. Nachman PH, Terrell RS, Jennette JC, Falk RJ: Naturally occurring anti-myeloperoxidase antibodies. Clin Exp Immunol 93 (Suppl 1):S18, 1993
  56. Jones DB, Coulson AFW, Duff GW: Sequence homologies between hsp60 and autoantigens. Immunol Today 14:115–118, 1993
  57. Audrain MAP, Baranger TAR, Lockwood CM, Esnault VLM: Characterization of mice monoclonals directed against commercially purified myeloperoxidase. Clin Exp Immunol 93 (Suppl 1):S18, 1993
  58. Coremans IEM, Hagen EC, Daha MR, Van Der Woude FJ, Van Der Voort EAM, Kleuburg-Van Der Keur C, Breedveld FC: Antilactoferrin antibodies in patients with rheumatoid arthritis are associated with vasculitis. Arthritis Rheum 35:1466–1475, 1992
  59. Mulder AHL, Broekroelofs J, Horst G, Limburg PC, Nelis GF, Kallenberg CGM: Anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease: Characterization and clinical correlates. Clin Exp Immunol 95:490–497, 1994
  60. Coremans IEM, Hagen EC, Daha MR, Van Der Woude FJ, Van Der Voort EAM, Breedveld FC: Anti-lactoferrin antibodies in patients with Felty's syndrome. Clin Exp Immunol 93 (Suppl 1):S33, 1993
  61. Lee SS, Lawton JWM, Chan CE: Antilactoferrin antibody in systemic lupus erythematosus. Br J Rheumatol 31:669–673, 1992 | Article | PubMed | ChemPort |
  62. Peen E, Almer S, Bodemar G, Ryder BO, Sjolin C, Tejle K, Skogh T: Anti-lactoferrin antibodies and other types of ANCA in ulcerative colitis, primary sclerosing cholangitis and Crohn's disease. Gut 34:56–62, 1993 | PubMed | ISI | ChemPort |
  63. Sinico RA, Pozzi C, Radice A, Tincani A, Li Vecchi M, Rota S, Comotti C, Ferrario F, D'Amico G: Clinical significance of antineutrophil cytoplasmic autoantibodies with specificity for lactoferrin in renal diseases. Am J Kidney Dis 22:253–260, 1993
  64. Gross WL, Schmitt WH, Csernok E: ANCA and associated diseases: Immunodiagnostic and pathogenetic aspects. Clin Exp Immunol 91:1–12, 1993 | PubMed | ISI | ChemPort |
  65. Cohen Tervaert JW, Mulder AHL, Stegeman CA, Elema JD, Huitema MG, The TH, Kallenberg CGM: The occurrence of autoantibodies to human leukocyte elastase in Wegener's Granulomatosis and other inflammatory disorders. Ann Rheum Dis 52:115–120, 1993 | PubMed |
  66. Halbwachs-Mecarelli LH, Nusbaum LH, Noël LH, Reumaux D, Erlinger S, Grünfeld 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 | PubMed | ChemPort |
  67. Kaneko K, Suzuki Y, Yamashiro Y, Yabuta S: Is p-ANCA in ulcerative colitis directed against glucuronidase? Lancet 341:320, 1993 | Article | PubMed | ISI | ChemPort |
  68. Moodie FDL, Leaker B, Cambridge G, Totty NF, Segal AW: Alpha-enolase: A novel cytosolic autoantigen in ANCA positive vasculitis. Kidney Int 43:675–681, 1993
  69. Nölle B, Specks U, Lüdemann J, Rohrbach MS, Deremee RA, Gross WL: Anticytoplasmic antibodies: Their immunodiagnostic value in Wegener's Granulomatosis. Ann Intern Med 111:28–40, 1989 | PubMed | ISI | ChemPort |
  70. Weber MFA, Andrassy K, Pullig O, Koderisch J, Netzer K: Antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies in Goodpasture's syndrome and in Wegener's granulomatosis. J Am Soc Nephrol 2:1227–1234, 1992 | PubMed | ISI | ChemPort |
  71. Kallenberg CGM, Cohen Tervaert JW: Anti-neutrophilic cytoplasmic antibodies: New tools in the diagnosis and follow-up of necrotizing glomerulonephritis, in International Yearbook of Nephrology 1992, edited by Andreucci VE, Fine LG, 1992, pp. 313–336
  72. Cohen Tervaert JW, Limburg PC, Elema JD, Huitema MG, Horst G, The TH, Kallenberg CGM: 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, 1991 | PubMed |
  73. Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, Calabrese LH, Fries JF, Lie JT, Lightfoot RW, Masi AT, McShane DJ, Mills JA, Stevens MB, Wallace SL, Zvaifler NJ: The American College of Rheumatology 1990 criteria for the classification of Wegener's Granulomatosis. Arthritis Rheum 33:1101–1107, 1990 | PubMed | ISI | ChemPort |
  74. Jennette JC, Falk RJ, Andrassy K, Bacon BA, Churg J, Gross WL, Hagen EC, Hoffmann GS, Hunder GG, Kallenberg CGM, McCluskey RT, Sinico RA, Rees AJ, Van Es LA, Waldherr R, Wiik A: Nomenclature of systemic vasculitides: The proposal of an international consensus conference. Arthritis Rheum 37:187–192, 1994 | Article | PubMed | ISI | ChemPort |
  75. Pudifin DJ, Duursma J, Gathiram V, Jackson TFGH: Serum from patients with invasive amoebiasis has anti-neutrophil cytoplasmic antibody activity. Clin Exp Immunol 93 (Suppl 1):S33, 1993
  76. Dolman KM, Gans ROB, Vervaart THJ, Zevenbergen G, Maingay D, Nikkels RE, Donker AJM, Von Dem Borne AEGKR, Goldschmeding R: Vasculitic disorders and antineutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy. Lancet 342:651–652, 1993 | Article | PubMed | ISI | ChemPort |
  77. Egner W, Chapel HM: Titration of antibodies against neutrophil cytoplasmic antigens is useful in monitoring disease activity in systemic vasculitides. Clin Exp Immunol 82:244–249, 1990 | PubMed | ISI | ChemPort |
  78. Cohen Tervaert JW, Huitema MG, Hené RJ, Sluiter WJ, The TH, Van Der Hem GK, Kallenberg CGM: Prevention of relapses in Wegener's granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre. Lancet 336:709–711, 1990 | PubMed |
  79. Kerr GR, Fleischer THA, Hallahan CW, Leavitt RY, Fauci AS, Hoffman GS: Limited prognostic value of changes in antineutrophil cytoplasmic antibody titer in patients with Wegener's granulomatosis. Arthritis Rheum 36:365–371, 1993 | PubMed | ISI | ChemPort |
  80. Cohen Tervaert JW, Stegeman CA, Huitema MG, Kallenberg CGM: Comments on article by Kerr et al. Arthritis Rheum (in press)
  81. Stegeman CA, Cohen Tervaert JW, Manson WL, Kallenberg CGM: Chronic nasal carriage of Staphylococcus aureus in Wegener's Granulomatosis: Identification of a subgroup more prone to relapses. Ann Intern Med 120:12–17, 1994 | PubMed | ISI | ChemPort |
  82. Spencer SJW, Burns A, Gaskin G, Pusey CD, Rees AJ: HLA class II specificities in vasculitis with antibodies to neutrophil cytoplasmic antigens. Kidney Int 41:1059–1063, 1992 | PubMed | ISI | ChemPort |
  83. Hunder GG, Arend WP, Bloch DA, Calabrese LH, Fauci AS, Fries JF, Leavitt RY, Lie JT, Lightfoot RW Jr, Masi AT, McShane DJ, Michel BA, Mills JA, Stevens MB, Wallace SC, Zvaifler NJ: The American College of Rheumatology 1990 criteria for the classification of vasculitis. Arthritis Rheum 33:1065–1067, 1990 | PubMed | ChemPort |
  84. Savage COS, Winearls CG, Evans DJ, Rees AJ, Lockwood CM: Microscopic polyarteritis: Presentation, pathology and prognosis. Q J Med 56:467–483, 1985 | PubMed | ISI | ChemPort |
  85. Gaskin G, Savage COS, Ryan JJ, Jones S, Lockwood CM, Rees AJ, Pusey CD: Anti-neutrophil cytoplasmic antibodies and disease activity during long-term follow-up of 70 patients with systemic vasculitis. Nephrol Dial Transplant 6:689–694, 1991 | PubMed | ISI | ChemPort |
  86. Jayne DRW, Marshall PD, Jones SJ, Lockwood CM: Autoantibodies to GBM and neutrophil cytoplasm in rapidly progressive glomerulonephritis. Kidney Int 37:965–970, 1990 | Article | PubMed | ISI | ChemPort |
  87. Bosch X, Mirapeix E, Font J, Borrellas X, Rodriquez R, Lopes-Soto A, Ingelmo M, Revert L: Prognostic implication of anti-neutrophil cytoplasmic autoantibodies with myeloperoxidase specificity in anti-glomerular basement membrane disease. Clin Nephrol 36:107–113, 1991 | PubMed | ISI | ChemPort |
  88. Niles JL, Pan G, Collins AB, Shannon T, Skates S, Fienberg R, Arnaout MA, McCluskey RT: Antigen-specific radioimmunoassay for anti-neutrophil cytoplasmic antibodies in the diagnosis of rapidly progressive glomerulonephritis. J Am Soc Nephrol 2:27–36, 1991 | PubMed | ISI | ChemPort |
  89. Cohen Tervaert JW, Goldschmeding R, Von Dem Borne AEGKR, Kallenberg CGM: Anti-myeloperoxidase antibodies in the Churg Strauss Syndrome. Thorax 46:70–71, 1991 | PubMed |
  90. Guillevin L, Visser H, Noël LH, Pourrat J, Vernier I, Gayraud M, Oksman F, Lesavre P: Antineutrophil cytoplasm antibodies in systemic polyarteritis nodosa with and without Hepatitis B Virus infection and Churg-Strauss syndrome. J Rheumatol 20:1345–1349, 1993 | PubMed | ISI | ChemPort |
  91. Gilbert RD, Shah V, Reader J, Dillon MJ: Cathepsin G specific IgM anti-neutrophil cytoplasmic antibodies (ANCA) and anti-endothelial cell antibodies (AECA) in acute Kawasaki disease. Clin Exp Immunol 93 (Suppl 1):S30, 1993
  92. Dagenais P, Dalpé G, Fernandes MF, Boire G, Keystone EC, Gross WL, Weyand MC, Ménard HA: ANCAs in patients with Takayasu's arteritis. Clin Exp Immunol 93 (Suppl 1):S34, 1993
  93. McHugh NJ, James IE, Plant G: Anticardiolipin and antineutrophil antibodies in giant cell arteritis. J Rheumatol 17:916–922, 1990 | PubMed | ISI | ChemPort |
  94. Van Der Wall Bake AWL, Lobatto S, Jonges L, Daha MR, Van Es LA: IgA antibodies directed against cytoplasmic antigens of polymorphonuclear leukocytes in patients with Henoch-Schönlein purpura. Adv Exp Med Biol 216:1593–1598, 1987
  95. Saulsbury T, Kirkpatrick PR, Bolton WK: IgA antineutrophil cytoplasmic antibody in Henoch-Schönlein purpura. Am J Nephrol 11:295–300, 1991
  96. Gueirard P, Delpech A, Gilbert D, Godin M, Le Loet X, Tron F: Anti-myeloperoxidase antibodies: Immunological characteristics and clinical associations. J Autoimmun 4:517–527, 1991 | Article | PubMed | ISI | ChemPort |
  97. Gallichio MC, Savige JA: Detection of anti-myeloperoxidase and anti-elastase antibodies in vasculitis and infections. Clin Exp Immunol 84:232–237, 1991 | PubMed |
  98. Nässberger L, Sjöholm AG, Jonsson H, Sturfelt G, Äkessen A: Autoantibodies against neutrophil cytoplasm components in systemic lupus erythematosus and in hydralazine-induced lupus. Clin Exp Immunol 81:380–383, 1990 | PubMed |
  99. Calabrese P, Edwards EA, Schilling RF: Fluorescent antiglobulin studies in leukopenic and related disorders. J Clin Invest 38:2091–2100, 1959
  100. Peter HH, Metzger D, Rump A, Röther E: ANCA in diseases other than systemic vasculitis. Clin Exp Immunol 93 (Suppl 1):S12–S14, 1993
  101. Duerr RH, Targan SR, Landers CJ, Sutherland LR, Shanahan F: Anti-neutrophil cytoplasmic antibodies in ulcerative colitis. Comparison with other colitides/diarrheal illnesses. Gastroenterology 100:1590–1596, 1991
  102. Saxon A, Sharahan 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 | Article | PubMed | ISI | ChemPort |
  103. Rump JA, Schölmerich J, Gross V, Roth M, Helfesrieder R, Rautmann A, Lüdemann J, Gross WL: A new type of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in active ulcerative colitis but not in Crohn's disease. Immunobiology 181:406–413, 1991
  104. Cambridge G, Rampton DS, Stevens TRJ, McCarthy DA, Kamm M, Leaker B: Anti-neutrophil antibodies in inflammatory bowel diseases: Prevalence and diagnostic role. Gut 33:668–674, 1992 | PubMed | ISI | ChemPort |
  105. 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: Relation to disease pattern and disease activity. Dig Dis Sci (in press)
  106. 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 | PubMed | ISI | ChemPort |
  107. Mulder AHL, Horst G, Haagsma EB, Limburg PC, Kleibeuker JH, Kallenberg CGM: Prevalence and characterization of anti-neutrophil cytoplasmic antibodies in autoimmune liver diseases. Hepatology 17:411–417, 1993 | Article | PubMed | ISI | ChemPort |
  108. Klaassen RJL, Goldschmeding R, Dolman KM, Vlekke ABJ, Weigel HM, Eeftinck Schattenkerk JKM, Mulder JW, Westedt ML, Von Dem Borne AEGKR: Anti-neutrophil cytoplasmic autoantibodies in patients with symptomatic HIV infection. Clin Exp Immunol 87:24–30, 1992 | PubMed | ISI | ChemPort |
  109. Efthiniou J, Spickett G, Lane D, Thompson A: Anti-neutrophil cytoplasmic antibodies, cystic fibrosis and infection. Lancet 337:1037–1038, 1991
  110. Dolman KM, Stegeman CA, Van De Wiel BA, Hack CE, Von Dem Borne AEGKR, Kallenberg CGM, Goldschmeding R: Relevance of classic anti-neutrophil cytoplasmic autoantibody (c-ANCA)-mediated inhibition of proteinase 3-alpha1-antitrypsin complexation to disease activity in Wegener's Granulomatosis. Clin Exp Immunol 93:405–410, 1993 | PubMed | ISI | ChemPort |
  111. Testa A, Audrain M, Baranger T, Sesboué R, Martin JP, Esnault VLM: Anti-neutrophil cytoplasm antibodies and alpha-1-antitrypsin phenotype. Clin Exp Immunol 93 (Suppl 1):S16, 1993
  112. Savage COS, Gaskin G, Pusey CD: Anti-neutrophil cytoplasm antibodies (ANCA) can recognize vascular endothelial cell-bound ANCA-associated autoantigens. J Exp Nephrol 1:190–195, 1993 | ChemPort |
  113. Ballieux BEPB, Zondervan K, Hagen EC, Van Der Woude FJ, Van Es LA, Daha MR: Differential binding of MPO and Pr3 to monolayers of endothelial cells. Clin Exp Immunol 93 (Suppl 1):S17, 1993
  114. Falk RJ, Terrell RS, Charles LA, Jennette JC: Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci USA 87:4115–4119, 1990 | Article | PubMed | ChemPort |
  115. Mulder AHL, Horst G, Limburg PC, Kallenberg CGM: Activation of neutrophils by anti-neutrophil cytoplasmic antibodies is FcR-dependent. Clin Exp Immunol 93 (Suppl 1):S16, 1993
  116. Porges AJ, Redecha PB, Csernok E, Gross WL, Kimberly RP: Monoclonal ANCA (anti-MPO and anti-Pr3) engage and activate neutrophils via Fcgamma Receptor IIA. Clin Exp Immunol 93 (Suppl 1):S18, 1993
  117. Brouwer E, Cohen Tervaert JW, Horst G, Huitema MG, Van Der Giessen M, Limburg PC, Kallenberg CGM: Predominance of IgG1 and IgG4 subclasses of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients with Wegener's granulomatosis and related disorders. Clin Exp Immunol 83:379–386, 1991 | PubMed | ISI | ChemPort |
  118. Fujimoto T, Lockwood CM: Antineutrophil cytoplasm antibodies (ANCA) activate protein kinase C in human neutrophils and HL-60 cells. (abstract) Am J Kidney Dis 18:204, 1991
  119. Lai KN, Lockwood CM: The effect of anti-neutrophil cytoplasm antibodies on the signal transduction in human neutrophils. Clin Exp Immunol 85:396–401, 1991 | PubMed | ISI | ChemPort |
  120. Jennette JC, Ewert BH, Falk RJ: Do antineutrophil cytoplasmic autoantibodies cause Wegener's granulomatosis and other forms of necrotizing vasculitis? Rheum Dis Clin N Am 19:1–28, 1993
  121. Savage COS, Pottinger BE, Gaskin G, Pusey CD, Pearson JD: Autoantibodies developing to myeloperoxidase and proteinase 3 in systemic vasculitis stimulate neutrophil cytotoxicity towards cultured endothelial cells. Am J Pathol 141:335–342, 1992 | PubMed | ISI | ChemPort |
  122. Ewert BH, Jennette JC, Falk RJ: Anti-myeloperoxidase antibodies stimulate neutrophils to damage human endothelial cells. Kidney Int 41:375–383, 1992 | PubMed | ISI | ChemPort |
  123. Keogan MT, Rifkin I, Ronda N, Lockwood CM, Brown DL: Antineutrophil cytoplasm antibodies increase neutrophil adhesion to cultured human endothelium. Adv Exp Med Biol 336:115–119, 1993 | PubMed |
  124. Brouwer E, Huitema MG, Mulder AHL, Heeringa P, Van Goor H, Cohen Tervaert JW, Weening JJ, Kallenberg CGM: Neutrophil activation in vitro and in vivo in Wegener's granulomatosis. Kidney Int 45:1121–1131, 1994
  125. Gephardt GN, Ahmed M, Tubbs RR: Pulmonary vasculitis (Wegener's granulomatosis). Immunohistochemical study of T and B cell markers. Am J Med 74:700–704, 1983 | Article | PubMed | ChemPort |
  126. Ten Berge RJM, Wilmink JM, Meyer CHRJLM, Surachno J, ten Veen KH, Balk TG, Schellekens PT: Clinical and immunological follow-up in patients with severe renal disease in Wegener's granulomatosis. Am J Nephrol 5:21–29, 1985
  127. Schmitt WH, Heesen C, Csernok E, Gross WL: Elevated serum levels of soluble interleukin-2-receptor (sIL-2R) in Wegener's granulomatosis: Association with disease activity. Arthritis Rheum 35:108–112, 1992
  128. Stegeman CA, Cohen Tervaert JW, Huitema MG, Kallenberg CGM: Serum markers of T-cell activation in relapses of Wegener's Granulomatosis. Clin Exp Immunol 91:415–420, 1993 | PubMed | ISI | ChemPort |
  129. Van Der Woude FJ, Van Es LA, Daha MR: The role of the c-ANCA antigen in the pathogenesis of Wegener's granulomatosis. A hypothesis based on both humoral and cellular mechanisms. Neth J Med 36:169–171, 1990 | PubMed |
  130. Petersen J, Rasmussen N, Szpiat W, Hermann E, Mayet W: T lymphocyte proliferation to neutrophil cytoplasmic antigen(s) in Wegener's granulomatosis. Am J Kidney Dis 18:205, 1991
  131. Brouwer E, Stegeman CA, Huitema MG, Limburg PC, Kallenberg CGM: T-cell reactivity to proteinase 3 and myeloperoxidase in patients with Wegener's granulomatosis. (submitted for publication)
  132. Kobayashi K, Shibata T, Sugisaki T: Aggravation of rat Masugi nephritis by heterologous anti-rat myeloperoxidase antibody. Clin Exp Immunol 93 (Suppl 1):S20, 1993
  133. Brouwer E, Huitema MG, Klok PA, Weerd HDE, Cohen Tervaert JW, Weening JJ, Kallenberg CGM: Anti-myeloperoxidase-associated proliferative glomerulonephritis: An animal model. J Exp Med 177:905–914, 1993 | Article | PubMed | ISI | ChemPort |
  134. Yang JJ, Tuttle R, Jennette JC, Falk RJ: Glomerulonephritis in rats immunized with myeloperoxidase. Clin Exp Immunol 93 (Suppl 1):S22, 1993
  135. Mathieson PW, Thiru S, Oliveira DBG: Mercuric chloridetreated Brown Norway rats develop widespread tissue injury including necrotizing vasculitis. Lab Invest 67:121–129, 1992 | PubMed |
  136. Fauci AS, Katz P, Haynes BF, Wolff SM: Cyclophosphamide therapy of severe systemic necrotizing vasculitis. N Engl J Med 301:235–238, 1979
  137. Fauci AS, Haynes BF, Katz P, Wolff SM: Wegener's Granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 98:76–85, 1983 | PubMed | ISI | ChemPort |
  138. Serra A, Cameron JS, Turner DR, Hartley B, Ogg CS, Nield GH, Williams DG, Taube D, Brown CB, Hicks JA: Vasculitis affecting the kidney. Presentation, histopathology and long-term outcome. Q J Med 53:181–207, 1984 | PubMed | ISI | ChemPort |
  139. Bradley JD, Brandt KD, Katz BP: Infectious complications of cyclophosphamide treatment for vasculitis. Arthritis Rheum 32:45–53, 1989
  140. Stillwall TJ, Benson RC, Deremee RA, McDonald TJ, Weiland LH: Cyclophosphamide-induced bladder toxicity in Wegener's Granulomatosis. Arthritis Rheum 31:465–470, 1988
  141. Balow JE, Austin HA, Tsokos CG, Antonovych TT, Steinberg AD, Klippel JH: Lupus nephritis. Ann Intern Med 106:79–94, 1987 | PubMed | ISI | ChemPort |
  142. Hoffman GS, Leavitt RY, Fleisher THA, Minor JR, Fauci AS: Treatment of Wegener's Granulomatosis with intermittent high-dose intravenous cyclophosphamide. Am J Med 89:403–410, 1990
  143. Falk JR, Hogan S, Carey TS, Jennette JC: Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. Ann Intern Med 113:656–663, 1990
  144. Adu D, Pall A, Lugmani RA, Richards N, Howie AJ, Emery P, Michael J, Bacon PA: Controlled trial of treatment of vasculitis. Clin Exp Immunol 93 (Suppl 1):38, 1993
  145. Deremee RA: The treatment of Wegener's Granulomatosis with trimethoprim/sulfamethoxazole: Illusion or vision? Arthritis Rheum 31:1068–1072, 1988
  146. Reinhold-Keller E, Beigel A, Duncker G, Heller M, Gross WL: Trimethoprim/sulfamethoxazole in the long-term treatment of Wegener's granulomatosis. Clin Exp Immunol 93 (Suppl 1):38, 1993
  147. Pinching AJ, Rees AJ, Pussell BA, Lockwood CM, Mitchison RS, Peters DK: Relapses in Wegener's granulomatosis: The role of infection. Br Med J 281:836–838, 1980 | PubMed |
  148. Pusey CD, Rees AJ, Evans DJ, Peters DK, Lockwood CM: Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies. Kidney Int 40:757–763, 1991 | PubMed | ISI | ChemPort |
  149. Bolton WK, Sturgill BC: Methylprednisolone therapy for acute crescentic rapidly progressive nephritis. Am J Nephrol 9:368–375, 1989
  150. Rossi F, Jayne DRW, Lockwood CM, Kazatchkine MD: Anti-idiotypes against anti-neutrophil cytoplasmic antigen autoantibodies in normal human polyspecific IgG for therapeutic use and in the remission sera of patients with systemic vasculitis. Clin Exp Immunol 83:298–303, 1991 | PubMed | ISI | ChemPort |
  151. Jayne DRW, Davies MJ, Fox CJV, Black CM, Lockwood CM: Treatment of systemic vasculitis with pooled intravenous immunoglobulin. Lancet 337:1137–1139, 1991 | Article | PubMed | ISI | ChemPort |
  152. Mathieson PW, Cobbold SP, Hale G, Clark MR, Oliveira DBG, Lockwood CM, Waldmann H: Monoclonal-antibody therapy in systemic vasculitis. N Engl J Med 323:250–254, 1990
  153. Lockwood CM, Thiru S, Isaacs JD, Hale G, Waldmann H: Long-term remission of intractable systemic vasculitis with monoclonal antibody therapy. Lancet 341:1620–1622, 1993 | Article | PubMed | ChemPort |

Extra navigation

.
ADVERTISEMENT