19
Views
1
CrossRef citations to date
0
Altmetric
Review

Pathogenic mechanisms of anti-neutrophil cytoplasm antibody-associated vasculitis

, &
Pages 543-555 | Published online: 10 Jan 2014

References

  • Watts RA, Gonzalez-Gay MA, Lane SE, Garcia-Porrua C, Bentham G, Scott DGI. Geoepidemiology of systemic vasculitis: comparison of the incidence in two regions of Europe. Ann. Rheum. Dis.60(2), 170–172 (2001).
  • Harper L, Savage COS. Pathogenesis of ANCA-associated systemic vasculitis. J. Path.190(3), 349–359 (2000).
  • Sanders JS, Huitma MG, Kallenberg CG, Stegeman CA. Prediction of relapses in PR3-ANCA-associated vasculitis by assessing responses of ANCA titres to treatment. Rheumatology (Oxf.)45(6), 724–729 (2006).
  • Pagnoux C, Guilpain P, Guillevin L. Churg–Strauss syndrome. Curr. Opin. Rheum.19(1), 25–32 (2007).
  • Bosch X, Guilabert A, Font J. Antineutrophil cytoplasmic antibodies. Lancet368(9533), 404–418 (2006).
  • Voswinkel J, Mueller A, Kraemer JA et al. B lymphocyte maturation in Wegener’s granulomatosis: a comparative analysis of VH genes from endonasal lesions. Ann. Rheum. Dis.65(7), 859–864 (2006).
  • Haas M, Eustace JA. Immune complex deposits in ANCA-associated crescentic glomerulonephritis: a study of 126 cases. Kidney Int.65(6), 2145–2152 (2004).
  • Brons RH, De Jong MCJM, de Boer NK, Stegeman CA, Kallenberg CGM, Tervaert JWC. Detection of immune deposits in skin lesions of patients with Wegener’s granulomatosis. Ann. Rheum. Dis.60(12), 1097–1102 (2001).
  • Persson U, Truedsson L, Westman KWA, Segelmark M. C3 and C4 allotypes in anti-neutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis. Clin. Exp. Immunol.116(2), 379–382 (1999).
  • Lane SE, Watts RA, Bentham G, Innes NJ, Scott DGI. Are environmental factors important in primary systemic vasculitis? A case–control study. Arthritis Rheum.48(3), 814–823 (2003).
  • Yashiro M, Muso E, Itoh-Ihara T et al. Significantly high regional morbidity of MPO-ANCA-related angitis and/or nephritis with respiratory tract involvement after the 1995 great earthquake in Kobe (Japan). Am. J. Kid. Dis.35(5), 889–895 (2000).
  • Patry YC, Trewick DC, Gregoire M et al. Rats injected with syngenic rat apoptotic neutrophils develop antineutrophil cytoplasmic antibodies. J. Am. Soc. Nephrol.12(8), 1764–1768 (2001).
  • Zheng LM, He M, Long M, Blomgran R, Stendahl O. Pathogen-induced apoptotic neutrophils express heat shock proteins and elicit activation of human macrophages. J. Immunol.173(10), 6319–6326 (2004).
  • Clayton AR, Prue RL, Harper L, Drayson MT, Savage COS. Dendritic cell uptake of human apoptotic and necrotic neutrophils inhibits CD40, CD80, and CD86 expression and reduces allogeneic T cell responses – relevance to systemic vasculitis. Arthritis Rheum.48(8), 2362–2374 (2003).
  • Stegeman CA, Tervaert JWC, Sluiter WJ, Manson WL, Dejong PE, Kallenberg CGM. Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann. Int. Med.120(1), 12–17 (1994).
  • Brons RH, Bakker HI, Van Wijk RT et al. Staphylococcal acid phosphatase binds to endothelial cells via charge interaction; a pathogenic role in Wegener’s granulomatosis? Clin. Exp. Immunol.119(3), 566–573 (2000).
  • Pendergraft WF, Preston GA, Shah RR et al. Autoimmunity is triggered by cPR-3(105–201), a protein complementary to human autoantigen proteinase-3. Nat. Med.10(1), 72–79 (2004).
  • Esnault VLM. Apoptosis: the central actor in the three hits that trigger anti-neutrophil cytoplasmic antibody-related systemic vasculitis. Nephrol. Dial. Transplant.17(10), 1725–1728 (2002).
  • Zhao MH, Chen M, Gao Y, Wang HY. Propylthiouracil-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int.69(8), 1477–1481 (2006).
  • Schlieben DJ, Korbet SM, Kimura RE, Schwartz MM, Lewis EJ. Pulmonary–renal syndrome in a newborn with placental transmission of ANCAs. Am. J. Kid. Dis.46(1), 171 (2005).
  • Jayne DRW, Gaskin G, Rasmussen N et al. Randomised trial of plasma exchange or high dose methyl prednisolone as adjunctive therapy for severe renal vasculitis. J. Am. Soc. Nephrol.18(7), (2007) (In Press).
  • Heeringa P, Brouwer E, Tervaert JWC, Weening JJ, Kallenberg CGM. Animal models of anti-neutrophil cytoplasmic antibody associated vasculitis. Kid. Int.53(2), 253–263 (1998).
  • Xiao H, Heeringa P, Hu P et al. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J. Clin. Invest.110(7), 955–963 (2002).
  • Xiao H, Schreiber A, Heeringa P, Falk RJ, Jennette JC. Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am. J. Path.170(1), 52–64 (2007).
  • Huugen D, Van Esch A, Xiao H et al. Inhibition of complement factor C5 protects against anti-myeloperoxidase antibody-mediated glomerulonephritis in mice. Kidney Int.71(7), 646–654 (2007).
  • Schreiber A, Xiao H, Falk RJ, Jennette JC. Bone marrow-derived cells are sufficient and necessary targets to mediate glomerulonephritis and vasculitis induced by anti-myeloperoxidase antibodies. J. Am. Soc. Nephrol.17(12), 3355–3364 (2006).
  • Little MA, Smyth CL, Yadav R et al. Antineutrophil cytoplasm antibodies directed against myeloperoxidase augment leukocyte–microvascular interactions in vivo. Blood106(6), 2050–2058 (2005).
  • Pfister H, Ollert M, Frohlich LF et al. Antineutrophil cytoplasmic autoantibodies against the murine homolog of proteinase 3 (Wegener autoantigen) are pathogenic in vivo. Blood104(5), 1411–1418 (2004).
  • Weidebach W, Viana VS, Leon EP et al. C-ANCA-positive IgG fraction from patients with Wegener’s granulomatosis induces lung vasculitis in rats. Clin. Exp. Immunol.129(1), 54–60 (2002).
  • Neumann I, Birck R, Newman M et al. SCG/Kinjoh mice: a model of ANCA-associated crescentic glomerulonephritis with immune deposits. Kidney Int.64(1), 140–148 (2003).
  • Hamano Y, Tsukamoto K, Abe M et al. Genetic dissection of vasculitis, myeloperoxidase-specific antineutrophil cytoplasmic autoantibody production, and related traits in spontaneous crescentic glomerulonephritis-forming/Kinjoh mice. J. Immunol.176(6), 3662–3673 (2006).
  • Schreiber A, Busjahn A, Luft FC, Kettritz R. Membrane expression of proteinase 3 is genetically determined. J. Am. Soc. Nephrol.14(1), 68–75 (2003).
  • Witko-Sarsat V, Lesavre P, Lopez S et al. A large subset of neutrophils expressing membrane proteinase 3 is a risk factor for vasculitis and rheumatoid arthritis. J. Am. Soc. Nephrol.10(6), 1224–1233 (1999).
  • von Vietinghoff S, Busjahn A, Schonemann C et al. Major histocompatibility complex HLA region largely explains the genetic variance exercised on neutrophil membrane proteinase 3 expression. J. Am. Soc. Nephrol.17(11), 3185–3191 (2006).
  • Yang JJ, Pendergraft WF, Alcorta DA et al. Circumvention of normal constraints on granule protein gene expression in peripheral blood neutrophils and monocytes of patients with antineutrophil cytoplasmic autoantibody-associated glomerulonephritis. J. Am. Soc. Nephrol.15(8), 2103–2114 (2004).
  • Ohlsson S, Wieslander I, Segelmark M. Increased circulating levels of proteinase 3 in patients with anti-neutrophilic cytoplasmic autoantibodies-associated systemic vasculitis in remission. Clin. Exp. Immunol.131(3), 528–535 (2003).
  • Abdgawad M, Hellmark T, Gunnarsson L, Westman KW, Segelmark M. Increased neutrophil membrane expression and plasma level of proteinase 3 in systemic vasculitis are not a consequence of the -564 A/G promotor polymorphism. Clin. Exp. Immunol.145(1), 63–70 (2006).
  • Novick D, Rubinstein M, Azam T, Rabinkov A, Dinarello CA, Kim SH. Proteinase 3 is an IL-32 binding protein. Proc. Natl Acad. Sci.103(9), 3316–3321 (2006).
  • Griffith ME, Coulthart A, Pemberton S, George AJ, Pusey CD. Anti-neutrophil cytoplasmic antibodies (ANCA) from patients with systemic vasculitis recognize restricted epitopes of proteinase 3 involving the catalytic site. Clin. Exp. Immunol.123(1), 170–177 (2001).
  • Hess C, Sadallah S, Schifferli JA. Induction of neutrophil responsiveness to myeloperoxidase antibodies by their exposure to supernatant of degranulated autologous neutrophils. Blood96(8), 2822–2827 (2000).
  • Harper L, Ren Y, Savill J, Adu D, Savage COS. Antineutrophil cytoplasmic antibodies induce reactive oxygen-dependent dysregulation of primed neutrophil apoptosis and clearance by macrophages. Am. J. Path.157(1), 211–220 (2000).
  • Harper L, Cockwell P, Adu D, Savage CO. Neutrophil priming and apoptosis in anti-neutrophil cytoplasmic autoantibody-associated vasculitis. Kidney Int.59(5), 1729–1738 (2001).
  • Moosig F, Csernok E, Kumanovics G, Gross WL. Opsonization of apoptotic neutrophils by anti-neutrophil cytoplasmic antibodies (ANCA) leads to enhanced uptake by macrophages and increased release of tumour necrosis factor-α (TNF-α). Clin. Exp. Immunol.122(3), 499–503 (2000).
  • Johnson PA, Alexander HD, McMillan SA, Maxwell AP. Up-regulation of the granulocyte adhesion molecule Mac-1 by autoantibodies in autoimmune vasculitis. Clin. Exp. Immunol.107(3), 513–519 (1997).
  • Radford DJ, Luu NT, Hewins P, Nash GB, Savage COS. Antineutrophil cytoplasmic antibodies stabilize adhesion and promote migration of flowing neutrophils on endothelial cells. Arthritis Rheum.44(12), 2851–2861 (2001).
  • Tse WY, Nash GB, Hewins P, Savage CO, Adu D. ANCA-induced neutrophil F-actin polymerization: implications for microvascular inflammation. Kidney Int.67(1), 130–139 (2005).
  • Cockwell P, Brooks CJ, Adu D, Savage CO. Interleukin-8: A pathogenetic role in antineutrophil cytoplasmic autoantibody-associated glomerulonephritis. Kidney Int.55(3), 852–863 (1999).
  • Hewins P, Williams JM, Wakelam MJ, Savage CO. Activation of Syk in neutrophils by antineutrophil cytoplasm antibodies occurs via Fcγ receptors and CD18. J. Am. Soc. Nephrol.15(3), 796–808 (2004).
  • Williams JM, Ben-Smith A, Hewins P et al. Activation of the G(i) heterotrimeric G protein by ANCA IgG F(ab´)2 fragments is necessary but not sufficient to stimulate the recruitment of those downstream mediators used by intact ANCA IgG. J. Am. Soc. Nephrol.14(3), 661–669 (2003).
  • Williams JM, Kamesh L, Savage COS. Translating basic science into patient therapy for ANCA-associated small vessel vasculitis. Clin. Sci.108(2), 101–112 (2005).
  • Williams JM, Savage CO. Characterization of the regulation and functional consequences of p21ras activation in neutrophils by antineutrophil cytoplasm antibodies. J. Am. Soc. Nephrol.16(1), 90–96 (2005).
  • Reumaux D, Kuijpers TW, Hordijk PL, Duthilleul P, Roos D. Involvement of Fcγ receptors and β2 integrins in neutrophil activation by anti-proteinase-3 or anti-myeloperoxidase antibodies. Clin. Exp. Immunol.134(2), 344–350 (2003).
  • Karussis D, Abramsky O, Grigoriadis N et al. The Ras-pathway inhibitor, S-trans-trans-farnesylthiosalicylic acid, suppresses experimental allergic encephalomyelitis. J. Neuroimmunol.120(1–2), 1–9 (2001).
  • Lu X, Garfield A, Rainger GE, Savage CO, Nash GB. Mediation of endothelial cell damage by serine proteases, but not superoxide, released from antineutrophil cytoplasmic antibody-stimulated neutrophils. Arthritis Rheum.54(5), 1619–1628 (2006).
  • Pendergraft WF, Alcorta DA, Segelmark M et al. ANCA antigens, proteinase 3 and myeloperoxidase, are not expressed in endothelial cells. Kidney Int.57(5), 1981–1990 (2000).
  • Pendergraft WF, Rudolph EH, Falk RJ et al. Proteinase 3 sidesteps caspases and cleaves p21(Waf1/Cip1/Sdi1) to induce endothelial cell apoptosis. Kidney Int.65(1), 75–84 (2004).
  • Yang JJ, Preston GA, Pendergraft WF et al. Internalization of proteinase 3 is concomitant with endothelial cell apoptosis and internalization of myeloperoxidase with generation of intracellular oxidants. Am. J. Pathol.158(2), 581–592 (2001).
  • Hooke DH, Gee DC, Atkins RC. Leukocyte analysis using monoclonal-antibodies in human glomerulonephritis. Kidney Int.31(4), 964–972 (1987).
  • Weidner S, Neupert W, Goppelt-Struebe M, Rupprecht HD. Antineutrophil cytoplasmic antibodies induce human monocytes to produce oxygen radicals in vitro. Arthritis Rheum.44(7), 1698–1706 (2001).
  • Wikman A, Fagergren A, Forslid J, Jacobson SH, Johansson SG, Lundahl J. Antineutrophil cytoplasmic antibodies induce decreased CD62L expression and enhanced metabolic activity in monocytes. Scand. J. Immunol.57(2), 179–184 (2003).
  • Nowack R, Schwalbe K, Flores-Suarez LF, Yard B, Van Der Woude FJ. Upregulation of CD14 and CD18 on monocytes in vitro by antineutrophil cytoplasmic autoantibodies. J. Am. Soc. Nephrol.11(9), 1639–1646 (2000).
  • Xiao H, Heeringa P, Liu Z et al. The role of neutrophils in the induction of glomerulonephritis by anti-myeloperoxidase antibodies. Am. J. Path.167(1), 39–45 (2005).
  • Feldmann M, Pusey CD. Is there a role for TNF-α in anti-neutrophil cytoplasmic antibody-associated vasculitis? Lessons from other chronic inflammatory diseases. J. Am. Soc. Nephrol.17(5), 1243–1252 (2006).
  • Jonasdottir O, Petersen J, Bendtzen K. Tumour necrosis factor-α (TNF), lymphotoxin and TNF receptor levels in serum from patients with Wegener’s granulomatosis. APMIS109(11), 781–786 (2001).
  • Huugen D, Xiao H, van Esch A et al. Aggravation of anti-myeloperoxidase antibody-induced glomerulonephritis by bacterial lipopolysaccharide: role of tumor necrosis factor-α. Am. J. Pathol.167(1), 47–58 (2005).
  • Little MA, Bhangal G, Smyth CL et al. Therapeutic effect of anti-TNF-α antibodies in an experimental model of anti-neutrophil cytoplasm antibody-associated systemic vasculitis. J. Am. Soc. Nephrol.17(1), 160–169 (2006).
  • The Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener’s granulomatosis. N. Engl. J. Med.352(4), 351–361 (2005).
  • Booth A, Harper L, Hammad T et al. Prospective study of TNFα blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. J. Am. Soc. Nephrol.15(3), 717–721 (2004).
  • Hewins P, Morgan MD, Holden N et al. IL-18 is upregulated in the kidney and primes neutrophil responsiveness in ANCA-associated vasculitis. Kidney Int.69(3), 605–615 (2006).
  • Tsuchiya N, Kobayashi S, Hashimoto H, Ozaki S, Tokunaga K. Association of HLA-DRB1*0901-DQB1*0303 haplotype with microscopic polyangiitis in Japanese. Genes Immun.7(1), 81–84 (2006).
  • Jagiello P, Gencik M, Arning L et al. New genomic region for Wegener’s granulomatosis as revealed by an extended association screen with 202 apoptosis-related genes. Hum. Genet.114(5), 468–477 (2004).
  • Marinaki S, Neumann I, Kalsch A-I et al. Abnormalities of CD4+ T cell subpopulations in ANCA-associated vasculitis. Clin. Exp. Immunol.140(1), 181–191 (2005).
  • Lamprecht P. Off balance: T-cells in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Clin. Exp. Immunol.141(2), 201–210 (2005).
  • Amyes E, McMichael AJ, Callan MFC. Human CD4+ T Cells are predominantly distributed among six phenotypically and functionally distinct subsets. J. Immunol.175(9), 5765–5773 (2005).
  • Tomiyama H, Matsuda T, Takiguchi M. Differentiation of human CD8(+) T cells from a memory to memory/effector phenotype. J. Immunol.168(11), 5538–5550 (2002).
  • Moosig F, Csernok E, Wang G, Gross WL. Costimulatory molecules in Wegener’s granulomatosis (WG): lack of expression of CD28 and preferential up-regulation of its ligands B7-1 (CD80) and B7-2 (CD86) on T cells. Clin. Exp. Immunol.114(1), 113–118 (1998).
  • Komocsi A, Lamprecht P, Csernok E et al. Peripheral blood and granuloma CD4(+)CD28(-) T cells are a major source of interferon-γ and tumor necrosis factor-α in Wegener’s granulomatosis. Am. J. Path.160(5), 1717–1724 (2002).
  • Abdulahad WH, van der Geld YM, Stegeman CA, Kallenberg CGM. Persistent expansion of CD4+ effector memory T cells in Wegener’s granulomatosis. Kidney Int.70(5), 938–947 (2006).
  • Lamprecht P, Bruhl H, Erdmann A et al. Differences in CCR5 expression on peripheral blood CD4(+)CD28(-) T-cells and in granulomatous lesions between localized and generalized Wegener’s granulomatosis. Clin. Immunol.108(1), 1–7 (2003).
  • Coulomb-L’Hermine A, Capron F, Zou WP et al. Expression of the chemokine RANTES in pulmonary Wegener’s granulomatosis. Hum. Path.32(3), 320–326 (2001).
  • Muller A, Trabandt A, Gloeckner-Hofmann K et al. Localized Wegener’s granulomatosis: Predominance of CD26 and IFN-γ expression. J. Path.192(1), 113–120 (2000).
  • Sibilia J, Benlagha K, Vanhille P, Ronco P, Brouet JC, Mariette X. Structural analysis of human antibodies to proteinase 3 from patients with Wegener granulomatosis. J. Immunol.159(2), 712–719 (1997).
  • Davis JA, Peen E, Williams RC et al. Determination of primary amino acid sequence and unique three-dimensional structure of WGH1, a monoclonal human IgM antibody with anti-PR3 specificity. Clin. Immunol. Immunopathol.89(1), 35–43 (1998).
  • Winek J, Mueller A, Csernok E, Gross WL, Lamprecht P. Frequency of proteinase 3 (PR3)-specific autoreactive T cells determined by cytokine flow cytometry in Wegener’s granulomatosis. J. Autoimmun.22(1), 79–85 (2004).
  • Giscombe R, Wang XB, Huang DR, Lefvert AK. Coding sequence 1 and promoter single nucleotide polymorphisms in the CTLA-4 gene in Wegener’s granulomatosis. J. Rheumatol.29(5), 950–953 (2002).
  • Jagiello P, Aries P, Arning L et al. The PTPN22 620W allele is a risk factor for Wegener’s granulomatosis. Arthritis Rheum.52(12), 4039–4043 (2005).
  • Mathieson PW, Cobbold SP, Hale G et al. Monoclonal-antibody therapy in systemic vasculitis. N. Eng. J. Med.323(4), 250–254 (1990).
  • Schmitt WH, Hagen EC, Neumann I, Nowack R, Flores-Suarez LF, Van Der Woude FJ. Treatment of refractory Wegener’s granulomatosis with antithymocyte globulin (ATG): an open study in 15 patients. Kidney Int.65(4), 1440–1448 (2004).
  • Yagi H, Nomura T, Nakamura K et al. Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int. Immunol.16(11), 1643–1656 (2004).
  • Culton DA, Nicholas MW, Bunch DO et al. Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss. J. Clin. Immunol.27(1), 53–68 (2007).
  • Specks U, Fervenza F, McDonald TJ, Hogan MCE. Response of Wegener’s granulomatosis to anti-CD20 chimeric monoclonal antibody therapy. Arthritis Rheum.44(12), 2836–2840 (2001).
  • Eriksson P. Nine patients with anti-neutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab. J. Internal Med.257(6), 540–548 (2005).
  • Ferraro AJ, Day CJ, Drayson MT, Savage CO. Effective therapeutic use of rituximab in refractory Wegener’s granulomatosis. Nephrol. Dial. Transplant.20(3), 622–625 (2005).
  • Keogh KA, Ytterberg SR, Fervenza FC, Carlson KA, Schroeder DR, Specks U. Rituximab for refractory Wegener’s granulomatosis. Report of a prospective, open label, pilot trial. Am. J. Respir. Crit. Care Med.173, 180–187 (2006).
  • Smith KG, Jones RB, Burns SM, Jayne DR. Long-term comparison of rituximab treatment for refractory systemic lupus erythematosus and vasculitis: remission, relapse, and re-treatment. Arthritis Rheum.54(9), 2970–2782 (2006).
  • Lund FE, Garvy BA, Randall TD, Harris DP. Regulatory role for cytokine-producing B cells in infection and autoimmune disease. In: B Cell Trophic Factors and B Cell Antagonism in Autoimmune Disease. Stohl W (Ed.). Karger, Basel, Switzerland 25–54 (2005).
  • Chan OT, Hannum LG, Haberman AM, Madaio MP, Shlomchik MJ. A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus. J. Exp. Med.189(10), 1639–1648 (1999).
  • Aries PM, Hellmich B, Voswinkel J et al. Lack of efficacy of rituximab in Wegener’s granulomatosis with refractory granulomatous manifestations. Ann. Rheum. Dis.65(7), 853–858 (2006).
  • Omdal R, Wildhagen K, Hansen T, Gunnarsson R, Kristoffersen G. Anti-CD20 therapy of treatment-resistant Wegener’s granulomatosis: favourable but temporary response. Scand. J. Rheum.34(3), 229–232 (2005).
  • Gong Q, Ou Q, Ye S et al. Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy. J. Immunol.174(2), 817–826 (2005).
  • Genberg H, Hansson A, Wernerson A, Wennberg L, Tyden G. Pharmacodynamics of rituximab in kidney allotransplantation. Am. J. Transpl.6(10), 2418–2428 (2006).
  • Birck R, Warnatz K, Lorenz HM et al. 15-deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis: a six-month open-label trial to evaluate safety and efficacy. J. Am. Soc. Nephrol.14(2), 440–447 (2003).
  • Schmitt WH, Birck R, Heinzel PA et al. Prolonged treatment of refractory Wegener’s granulomatosis with 15-deoxyspergualin: an open study in seven patients. Nephrol. Dial. Transplant.20(6), 1083–1092 (2005).
  • Kalsch AI, Schmitt WH, Breedijk A et al. In vivo effects of cyclic administration of 15-deoxyspergualin on leucocyte function in patients with Wegener’s granulomatosis. Clin. Exp. Immunol.146(3), 455–462 (2006).

Websites

  • Clinical Trials by EUVAS. European Vasculitis Study Group www.vasculitis.org/acttrials.htm
  • RAVE – Rituximab for ANCA associated Vasculitis. Immune Tolerance Network www.immunetolerance.org/rave/

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.