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VOLUME 3 , ISSUE 1--2 ( January-June, 2024 ) > List of Articles


Antineutrophil Cytoplasmic Antibodies-associated Vasculitis

Krešimir Galešić

Keywords : Antineutrophil cytoplasmic antibodies-associated vasculitis, Eosinophilic granulomatosis with polyangiitis or Churg–Strauss syndrome, Etiology, Granulomatosis with polyangiitis or Wegener's granulomatosis, Microscopic polyangiitis, Pathogenesis, Therapy

Citation Information : Galešić K. Antineutrophil Cytoplasmic Antibodies-associated Vasculitis. 2024; 3 (1--2):17-26.

DOI: 10.5005/jp-journals-11005-0071

License: CC BY-NC 4.0

Published Online: 27-03-2024

Copyright Statement:  Copyright © 2024; The Author(s).


Vasculitis related to antineutrophil cytoplasmic antibodies (ANCA) (ANCA-vasculitis) is an autoimmune disease that causes inflammation of small to medium-sized blood vessels with consequent damage and loss of function in certain organs. The ANCA-associated vasculitides are defined by specific pathological changes and associated autoimmune responses produced by ANCA antibodies. The nomenclature of vasculitis from the consensus conference in Chapel Hill defines ANCA-vasculitis as necrotizing vasculitis with little or no immune deposits and predominant involvement of small blood vessels (capillaries, venules, arterioles, and small arteries). There are two phases in the treatment of ANCA small vessel vasculitis—induction treatment and maintenance therapy.

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  1. Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides. Proposal of an International Consensus Conference. Arthritis Rheum 1994;37(2):187–192. DOI: 10.1002/art.1780370206
  2. Samarkos M, Loizou S, Vaiopoulos G, et al. The clinical spectrum of primary vasculitis. Semin Arthritis Rheum 2005;35(2):95–111. DOI: 10.1016/j.semarthrit.2005.05.004
  3. Jennette JC, Falk RJ. Small-vessel vasculitis. N Engl J Med 1997;337(21):1512–1523. DOI: 10.1056/NEJM199711203372106
  4. Mansi IA, Opran A, Rosner F. ANCA-associated small-vessels vasculitis. Am J Physic 2002;65(8):1615–1620. PMID: 11989638.
  5. Puechal X. Antineutrophil cytoplasmatic antibody-associated vasculitis. Joint Bone Spine 2007;74(5):427–435. DOI: 10.1016/j.jbspin.2007.02.001
  6. Passen P, Tervaert JWC, Hering P. Mechanisms of vasculitis: how pauci-immune is ANCA-associated renal vasculitis. Nephron Exp Nephrol 2007;105(1):e10–e16. DOI: 10.1159/000096960
  7. Kain R, Exner M, Brandes R, et al. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat Med 2008;14(10):1088–1096. DOI: 10.1038/nm.1874
  8. Bautz DJ, Preston GA, Lionaki S et al. Antibodies with dual reactivity to plasminogen and complementary PR3 in PR3-ANCA vasculitis. J Am Soc Nephrol 2008;19(12):2421–2429. DOI: 10.1681/ASN.2008030270
  9. Cao Y, Schmitz JL, Yang J, et al. DRB1*15 allele is a risk factor for PR3-ANCA disease in African Americans. J Am Soc Nephrol 2011;22(6):1161–1167. DOI: 10.1681/ASN.2010101058
  10. Marinaki S, Kälsch AI, Grimminger P, et al. Persistent T-cell activation and clinical correlations in patients with ANCA-associated systemic vasculitis. Nephrol Dial Transplant 2006;21(7):1825–1832. DOI: 10.1093/ndt/gfl097
  11. Albert D, Clarkin C, Komoroski J, et al. Wegener's granulomatosis: possible role of environmental agents in its pathogenesis. Arthritis Rheum 2004;51(4):656–664. DOI: 10.1002/art.20534
  12. Chen M, Yu F, Wang SX. Antineutrophil cytoplasmic autoantibodies-negative pauci-immune crescentic glomerulonephritis. J Am Soc Nephrol 2007;18(2):599–605. DOI: 10.1681/ASN.2006091021
  13. Sugimot T, Deji N, Kume S, et al. Pulmonary-renal syndrome, diffuse pulmonary hemorrhage and glomerulonphritis, associated with Wegener's granulomatosis effectively treated with early plasma exchange therapy. Intern Med 2007;46(1):49–53. DOI: 10.2169/internalmedicine.46.6070
  14. Bajema IM, Hagen EC, Hermans J. Kidney biopsy as a predictor for renal outcome in ANCA-associated necrotizing glomerulonephritis. Kidney Int 1999;56(5):1751–1758. DOI: 10.1046/j.1523-1755.1999.00758.x
  15. Bajema IM, Hagen EC, Hansen BE. The renal histopathology in systemic vasculitis: an international survey study of inter-and intra-observer agreement. Nephrol Dial Transplant 1996;11(10):1989–1995. DOI: 10.1093/oxfordjournals.ndt.a027086
  16. Luqmani RA, Bacon PA, Moots RJ, et al. Birmingham vasculitis activity score (BVAS) in systemic necrotizing vasculitis. QJM 1994;87(11):671–678. PMID: 7820541.
  17. Exley AR, Bacon PA, Luqmani RA, et al. Development and initial validation of the VDI. Arthritis Rheum 1997;40(2):371–380. DOI: 10.1002/art.1780400222
  18. Hauer A, Bajema IM, van Houwelingen HC. Renal histology in ANCA-associated vasculitis: differences between diagnostic and serologic subgroups. Kidney Int 2002;61(1):80–89. DOI: 10.1046/j.1523-1755.2002.00089.x
  19. Hauer HA, Bajema IM, van Houwelingen HC, et al. Long-term renal injury in ANCA-associated vasculitis: an analysis of 31 patients with follow-up biopsies. Nephrol Dial Transplant 2002;17(4):587–596. DOI: 10.1093/ndt/17.4.587
  20. Balow J, Fauci A. Vasculitic diseases of the kidney. In: Schrier WR, Gottschalk WC (Eds). Diseases of the Kidney. Boston: Little, Brown and Company; 1997. pp. 1851–1873.
  21. Csernok E, Ai M, Gross WL, et al. Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway. Blood 2006;107(11):4440–4448. DOI: 10.1182/blood-2005-05-1875
  22. Aasarød K, Bostad L, Hammerstrom J, et al. Renal histopathology and clinical course in 94 patients with Wegener's granulomatosis. Nephrol Dial Transplant 2001;16(5):953–960. DOI: 10.1093/ndt/16.5.953
  23. Jayne DR, Rasmussen N. Treatment of antineutrophil cytoplasm autoantibody-associated systemic vasculitis: initiatives of the European Community Systemic Vasculitis Clinical Trials Study Group. Mayo Clin Proc 1997;72(8):737–747. DOI: 10.1016/S0025-6196(11)63594-5
  24. Fauci AS, Wolff SM. Wegener's granulomatosis: studies in eighteen patients and review of the literature. Medicine 1973;52(6):535–561. DOI: 10.1097/00005792-197311000-00002
  25. Belmont HM. Treatment of ANCA-associated systemic vasculitis. Bull NYU Hosp Jt Dis 2006;64(1-2):60–66. PMID: 17121492.
  26. Walters GD, Willis NS, Craig JC. Interventions for renal vasculitis in adults. A systematic review. BMC Nephrol 2010;24:11–12. DOI: 10.1186/1471-2369-11-12
  27. Mukhtyar C, Guillevin L, Cid MC et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 2009;68(3):310–317. DOI: 10.1136/ard.2008.088096
  28. Jayne DR, Gaskin G, Rasmussen N, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 2007;18(7):2180–2188. DOI: 10.1681/ASN.2007010090
  29. Szpirt WM, Heaf JG, Petersen J. Plasma exchange for induction and cyclosporine A for maintenance of remission in Wegener's granulomatosis-a clinical randomized controlled trial. Nephrol Dial Transplant 2011;26(1):206–213. DOI: 10.1093/ndt/gfq360
  30. Walsh M, Catapano F, Szpirt W, et al. Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. Am J Kidney Dis 2011;57(4):566–574. DOI: 10.1053/j.ajkd.2010.10.049
  31. De Groot K, Harper L, Jayne DR, et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med 2009;150(10):670–680. DOI: 10.7326/0003-4819-150-10-200905190-00004
  32. Guillevin L, Cordier JF, Lhote F, et al. A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener's disease. Arthritis Rheum 1997;40(12):2187–2198. DOI: 10.1002/art.1780401213
  33. De Groot K, Rasmussen N, Bacon PA, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2005;52(8):2461–2469. DOI: 10.1002/art.21142
  34. Jones RB, Tervaert JW, Hauser T, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 2010;363(3):211–220. DOI: 10.1056/NEJMoa0909169
  35. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010;363(3):221–232. DOI: 10.1056/NEJMoa0909905
  36. Schmitt WH, Hagen EC, Neumann I, et al. Treatment of refractory Wegener's granulomatosis with antithymocyte globulin (ATG): an open study in 15 patients. Kidney Int 2004;65(4):1440–1448. DOI: 10.1111/j.1523-1755.2004.00534.x
  37. Birck R, Warnatz K, Lorenz HM, et al. 15-deoxypergualin in patients with refractory ANCA-associated systemic vasculitis: a six month open label trial to evaluate safety and efficacy. J Am Soc Nephrol 2003;14(2):440–447. DOI: 10.1097/01.asn.0000048716.42876.14
  38. Jayne D, Rasmussen N, Andrassy K, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003;349(1):36–44. DOI: 10.1056/NEJMoa020286
  39. Reinhod-Keller E, De Groot K, Rudert H, et al. Response to trimethoprim/sulfamethoxazole in Wegener's granulomatosis depends on the phases of disease. QJM 1996;89(1):15–23. DOI: 10.1093/oxfordjournals.qjmed.a030133
  40. Jayne DR, Chapel H, Adu D, et al. Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM 2000;93(7):433–439. DOI: 10.1093/qjmed/93.7.433
  41. Mahr A, Hamidou MA, Boffa JJ, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med 2008;359(26):2790–2803. DOI: 10.1056/NEJMoa0802311.
  42. Hiemstra TF, Walsh M, Mahr A, et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmatic antibody-associated vasculitis. JAMA 2010;304(21):2381–2388. DOI: 10.1001/jama.2010.1658
  43. Rhee EP, Laliberte KA, Niles JL. Rituximab as maintenance therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis. Clin J Am Soc Nephrol 2010;5(8):1394–1400. DOI: 10.2215/CJN.08821209
  44. Ferrero AJ, Day CJ, Drayson MT, et al. Effective therapeutic use of rituximab in refractory Wegener's granulomatosis. Nephrol Dial Transplant 2005;20(3):622–625. DOI: 10.1093/ndt/gfh599
  45. Chapter 13: pauci-immune focal and segmental necrotizing glomerulonephritis. Kidney Int Suppl (2011) 2012;2(2):233–239. DOI: 10.1038/kisup.2012.26
  46. Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med 2005;352(4):351–361. DOI: 10.1056/NEJMoa041884
  47. Booth A, Harper L, Hammad T, et al. Prospective study of TNFα blockade with infliximab in antineutrophil cytoplasmic antibody-associated systemic vasculitis. J Am Soc Nephrol 2004;15(3):717–721. DOI: 10.1097/01.asn.0000114554.67106.28
  48. Metzler C, Miehle N, Manger K, et al. Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener's granulomatosis. Rheumatology (Oxford) 2007;46(7):1087–1091. DOI: 10.1093/rheumatology/kem029
  49. Genovese MC, Becker JC, Schiff M, et al. Abatacept for rheumatoid arthritis refractory tumor necrosis factor alpha inhibition. N Engl J Med 2005;353(11):1114–1123. DOI: 10.1056/NEJMoa050524
  50. Hellmich B, Flossmann O, Gross WL, et al. EULAR recommendation for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on ANCA-associated vasculitis. Ann Rheum Dis 2007;66(5):605–617. DOI: 10.1136/ard.2006.062711
  51. Kaplan-Pavlovčić S, Cerk K, Kvered R, et al. Clinical prognostic factors of renal outcome in anti-neutrophil cytoplasmatic autoantibody (ANCA)—associated glomerulonephritis in elderly patients. Nephrol Dial Transplant 2003;18(Suppl 5):v5–v7. DOI: 10.1093/ndt/gfg1033
  52. Alexopulos E, Gionanlis L, Papayianni E, et al. Predictors of outcome in idiopathic rapidly progressive glomerulonephritis (IRPGN).BMC Nephrol 2006;7:16. DOI: 10.1186/1471-2369-7-16
  53. Hogan SL, Falk R, Chin H, et al. Predictors of relapse and treatment resistance in antineutrophil cytoplasmatic antibody-associated small-vessel vasculitis. Ann Intern Med 2005;143(9):621–631. DOI: 10.7326/0003-4819-143-9-200511010-00005
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