ANCA-associated vasculitis.
Journal
Nature reviews. Disease primers
ISSN: 2056-676X
Titre abrégé: Nat Rev Dis Primers
Pays: England
ID NLM: 101672103
Informations de publication
Date de publication:
27 08 2020
27 08 2020
Historique:
accepted:
14
07
2020
entrez:
29
8
2020
pubmed:
29
8
2020
medline:
16
6
2021
Statut:
epublish
Résumé
The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA
Identifiants
pubmed: 32855422
doi: 10.1038/s41572-020-0204-y
pii: 10.1038/s41572-020-0204-y
doi:
Substances chimiques
Immunosuppressive Agents
0
Peroxidase
EC 1.11.1.7
Myeloblastin
EC 3.4.21.76
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
71Subventions
Organisme : Medical Research Council
ID : MR/L019027/1
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 20593
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/13/64/30435
Pays : United Kingdom
Références
Watts, R. A. et al. Classification, epidemiology and clinical subgrouping of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Nephrol. Dial. Transplant. 30 (Suppl. 1), i14–i22 (2015). A granular and comprehensive review of contemporary AAV epidemiology.
pubmed: 25805746
Berti, A., Cornec, D., Crowson, C. S., Specks, U. & Matteson, E. L. The epidemiology of antineutrophil cytoplasmic autoantibody-associated vasculitis in Olmsted County, Minnesota: a twenty-year US population-based study. Arthritis Rheumatol. 69, 2338–2350 (2017).
pubmed: 28881446
pmcid: 5711593
Mohammad, A. J., Jacobsson, L. T., Mahr, A. D., Sturfelt, G. & Segelmark, M. Prevalence of Wegener’s granulomatosis, microscopic polyangiitis, polyarteritis nodosa and Churg-Strauss syndrome within a defined population in southern Sweden. Rheumatology 46, 1329–1337 (2007).
pubmed: 17553910
Tan, J. A. et al. Mortality in ANCA-associated vasculitis: a meta-analysis of observational studies. Ann. Rheum. Dis. 76, 1566–1574 (2017).
pubmed: 28468793
Basu, N. et al. The characterisation and determinants of quality of life in ANCA associated vasculitis. Ann. Rheum. Dis. 73, 207–211 (2014).
pubmed: 23355077
Raimundo, K., Farr, A. M., Kim, G. & Duna, G. Clinical and economic burden of antineutrophil cytoplasmic antibody-associated vasculitis in the United States. J. Rheumatol. 42, 2383–2391 (2015).
pubmed: 26523026
Knight, A., Ekbom, A., Brandt, L. & Askling, J. Increasing incidence of Wegener’s granulomatosis in Sweden, 1975–2001. J. Rheumatol. 33, 2060–2063 (2006).
pubmed: 16960922
Liu, L. J., Chen, M., Yu, F., Zhao, M. H. & Wang, H. Y. Evaluation of a new algorithm in classification of systemic vasculitis. Rheumatology 47, 708–712 (2008).
pubmed: 18390585
Watts, R. A. et al. Renal vasculitis in Japan and the UK — are there differences in epidemiology and clinical phenotype? Nephrol. Dial. Transpl. 23, 3928–3931 (2008).
Watts, R. A. et al. Geoepidemiology of systemic vasculitis: comparison of the incidence in two regions of Europe. Ann. Rheum. Dis. 60, 170–172 (2001).
pubmed: 11156552
pmcid: 1753459
O’Donnell, J. L., Stevanovic, V. R., Frampton, C., Stamp, L. K. & Chapman, P. T. Wegener’s granulomatosis in New Zealand: evidence for a latitude-dependent incidence gradient. Intern. Med. J. 37, 242–246 (2007).
pubmed: 17388864
Cao, Y. et al. DRB1*15 allele is a risk factor for PR3-ANCA disease in African Americans. J. Am. Soc. Nephrol. 22, 1161–1167 (2011).
pubmed: 21617122
pmcid: 3103736
Mahr, A., Guillevin, L., Poissonnet, M. & Ayme, S. Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener’s granulomatosis, and Churg-Strauss syndrome in a French urban multiethnic population in 2000: a capture-recapture estimate. Arthritis Rheumatol. 51, 92–99 (2004).
Pearce, F. A. et al. Incidence of ANCA-associated vasculitis in a UK mixed ethnicity population. Rheumatology 55, 1656–1663 (2016).
pubmed: 27274096
Iudici, M. et al. Childhood-onset granulomatosis with polyangiitis and microscopic polyangiitis: systematic review and meta-analysis. Orphanet J. Rare Dis. 11, 141 (2016).
pubmed: 27770813
pmcid: 5075395
Falk, R. J., Hogan, S., Carey, T. S. & Jennette, J. C. Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. Ann. Intern. Med. 113, 656–663 (1990).
pubmed: 2221646
Tidman, M., Olander, R., Svalander, C. & Danielsson, D. Patients hospitalized because of small vessel vasculitides with renal involvement in the period 1975-95: organ involvement, anti-neutrophil cytoplasmic antibodies patterns, seasonal attack rates and fluctuation of annual frequencies. J. Intern. Med. 244, 133–141 (1998).
pubmed: 10095799
Watts, R. A., Mooney, J., Skinner, J., Scott, D. G. & Macgregor, A. J. The contrasting epidemiology of granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis. Rheumatology 51, 926–931 (2012).
pubmed: 22258386
Draibe, J. et al. Seasonal variations in the onset of positive and negative renal ANCA-associated vasculitis in Spain. Clin. Kidney J. 11, 468–473 (2018).
pubmed: 30094010
Mahr, A. et al. Seasonal variations in onset of Wegener’s granulomatosis: increased in summer? J. Rheumatol. 33, 1615–1622 (2006).
pubmed: 16832845
Aries, P. M., Herlyn, K., Reinhold-Keller, E. & Latza, U. No seasonal variation in the onset of symptoms of 445 patients with ‘Wegener’s granulomatosis. Arthritis Rheumatol. 59, 904–904 (2008).
Stegeman, C. A. et al. Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann. Intern. Med. 120, 12–17 (1994). A study that provides evidence for a putative causal role for infection in the relapse of GPA.
pubmed: 8250451
Laudien, M. et al. Nasal carriage of Staphylococcus aureus and endonasal activity in Wegener’s granulomatosis as compared to rheumatoid arthritis and chronic rhinosinusitis with nasal polyps. Clin. Exp. Rheumatol. 28 (Suppl. 57), 51–55 (2010).
pubmed: 20412703
Lane, S. E., Watts, R. A., Bentham, G., Innes, N. J. & Scott, D. G. Are environmental factors important in primary systemic vasculitis? A case-control study. Arthritis Rheumatol. 48, 814–823 (2003).
Nuyts, G. D. et al. Wegener granulomatosis is associated to exposure to silicon-compounds-a case-control study. Nephrol. Dial. Transpl. 10, 1162–1165 (1995).
Yashiro, M. 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. Kidney Dis. 35, 889–895 (2000).
pubmed: 10793024
Takeuchi, Y. et al. The influence of the Great East Japan earthquake on microscopic polyangiitis: a retrospective observational study. PLoS ONE 12, e0177482 (2017).
pubmed: 28498830
pmcid: 5428958
Farquhar, H. J. et al. Incidence of anti-neutrophil cytoplasmic antibody-associated vasculitis before and after the February 2011 Christchurch Earthquake. Intern. Med. J. 47, 57–61 (2017).
pubmed: 27572474
Cotch, M. F. et al. The epidemiology of Wegener’s granulomatosis. Estimates of the five-year period prevalence, annual mortality, and geographic disease distribution from population-based data sources. Arthritis Rheumatol. 39, 87–92 (1996).
Li, J. et al. The frequency of ANCA-associated vasculitis in a national database of hospitalized patients in China. Arthritis Res. Ther. 20, 226 (2018).
pubmed: 30286799
pmcid: 6235226
Gatenby, P. A., Lucas, R. M., Engelsen, O., Ponsonby, A. L. & Clements, M. Antineutrophil cytoplasmic antibody-associated vasculitides: could geographic patterns be explained by ambient ultraviolet radiation? Arthritis Rheumatol. 61, 1417–1424 (2009).
McDermott, G. et al. Association of cigarette smoking with antineutrophil cytoplasmic antibody-associated vasculitis. JAMA Intern. Med. 180, 1–7 (2020).
Hutton, H. L., Holdsworth, S. R. & Kitching, A. R. ANCA-associated vasculitis: pathogenesis, models, and preclinical testing. Sem. Nephrol. 37, 418–435 (2017).
Knight, A., Sandin, S. & Askling, J. Risks and relative risks of Wegener’s granulomatosis among close relatives of patients with the disease. Arthritis Rheumatol. 58, 302–307 (2008).
Jagiello, P. et al. New genomic region for Wegener’s granulomatosis as revealed by an extended association screen with 202 apoptosis-related genes. Hum. Genet. 114, 468–477 (2004).
pubmed: 14968360
Lyons, P. A. et al. Genetically distinct subsets within ANCA-associated vasculitis. N. Engl. J. Med. 367, 214–223 (2012).
pubmed: 22808956
pmcid: 3773907
Xie, G. et al. Association of granulomatosis with polyangiitis (Wegener’s) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis. Arthritis Rheumatol. 65, 2457–2468 (2013).
Merkel, P. A. et al. Identification of functional and expression polymorphisms associated with risk for antineutrophil cytoplasmic autoantibody-associated vasculitis. Arthritis Rheumatol. 69, 1054–1066 (2017). Lyons et al. (2012), Xie et al. (2013) and Merkel et al. (2017) provide clear evidence for a genetic contribution to differences between PR3-AAV and MPO-AAV and link PR3-AAV to variation in the autoantigen itself.
pubmed: 28029757
pmcid: 5434905
Siminovitch, K. A. PTPN22 and autoimmune disease. Nat. Genet. 36, 1248–1249 (2004).
pubmed: 15565104
Sun, B. B. et al. Genomic atlas of the human plasma proteome. Nature 558, 73–79 (2018).
pubmed: 29875488
pmcid: 6697541
Niehrs, A. et al. A subset of HLA-DP molecules serve as ligands for the natural cytotoxicity receptor NKp44. Nat. Immunol. 20, 1129–1137 (2019).
pubmed: 31358998
Lyons, P. A. et al. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status. Nat. Commun. 10, 5120 (2019).
pubmed: 31719529
pmcid: 6851141
Sablé-Fourtassou, R. et al. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann. Intern. Med. 143, 632–638 (2005).
pubmed: 16263885
Sinico, R. A. et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome. Arthritis Rheumatol. 52, 2926–2935 (2005).
Nakazawa, D. et al. Enhanced formation and disordered regulation of NETs in myeloperoxidase-ANCA-associated microscopic polyangiitis. J. Am. Soc. Nephrol. 25, 990–997 (2014).
pubmed: 24385592
pmcid: 4005303
Ooi, J. D. et al. A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity. Nat. Comm. 10, 3392 (2019).
Jones, B. E. et al. Gene-specific DNA methylation changes predict remission in patients with ANCA-associated vasculitis. J. Am. Soc. Nephrol. 28, 1175–1187 (2017).
pubmed: 27821628
Kessenbrock, K. et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat. Med. 15, 623–625 (2009).
pubmed: 19448636
pmcid: 2760083
Martin, K. R. & Witko-Sarsat, V. Proteinase 3: the odd one out that became an autoantigen. J. Leuk. Biol. 102, 689–698 (2017).
Witko-Sarsat, V. 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, 1224–1233 (1999).
pubmed: 10361860
Jerke, U. et al. Complement receptor Mac-1 is an adaptor for NB1 (CD177)-mediated PR3-ANCA neutrophil activation. J. Biol. Chem. 286, 7070–7081 (2011).
pubmed: 21193407
Odobasic, D., Kitching, A. R. & Holdsworth, S. R. Neutrophil-mediated regulation of innate and adaptive immunity: the role of myeloperoxidase. J. Immunol. Res. 2016, 2349817 (2016).
pubmed: 26904693
pmcid: 4745373
Reiding, K. R. et al. Neutrophil myeloperoxidase harbors distinct site-specific peculiarities in its glycosylation. J. Biol. Chem. 294, 20233–20245 (2019).
pubmed: 31719144
pmcid: 6937560
Kain, R. et al. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat. Med. 14, 1088–1096 (2008).
pubmed: 18836458
pmcid: 2751601
Pendergraft, W. F. et al. Autoimmunity is triggered by cPR-3(105-201), a protein complementary to human autoantigen proteinase-3. Nat. Med. 10, 72–79 (2004).
pubmed: 14661018
Yang, J. et al. ANCA patients have T cells responsive to complementary PR-3 antigen. Kidney Int. 74, 1159–1169 (2008).
pubmed: 18596726
pmcid: 2754720
Suzuki, K. et al. A novel autoantibody against moesin in the serum of patients with MPO-ANCA-associated vasculitis. Nephrol. Dial. Transpl. 29, 1168–1177 (2014).
Bautz, D. J. et al. Antibodies with dual reactivity to plasminogen and complementary PR3 in PR3-ANCA vasculitis. J. Am. Soc. Nephrol. 19, 2421–2429 (2008).
pubmed: 18701607
pmcid: 2588098
Berden, A. E. et al. Anti-plasminogen antibodies compromise fibrinolysis and associate with renal histology in ANCA-associated vasculitis. J. Am. Soc. Nephrol. 21, 2169–2179 (2010).
pubmed: 20847144
pmcid: 3014030
McCall, A. S. et al. Inhibitory anti-peroxidasin antibodies in pulmonary-renal syndromes. J. Am. Soc. Nephrol. 29, 2619–2625 (2018).
pubmed: 30279272
pmcid: 6218858
Simon, A. et al. Detection of anti-pentraxin-3 autoantibodies in ANCA-associated vasculitis. PLoS ONE 11, e0147091 (2016).
pubmed: 26797217
pmcid: 4721655
Roth, A. J. et al. Anti-LAMP-2 antibodies are not prevalent in patients with antineutrophil cytoplasmic autoantibody glomerulonephritis. J. Am. Soc. Nephrol. 23, 545–555 (2012).
pubmed: 22021709
pmcid: 3294309
Tadema, H., Kallenberg, C. G., Stegeman, C. A. & Heeringa, P. Reactivity against complementary proteinase-3 is not increased in patients with PR3-ANCA-associated vasculitis. PLoS ONE 6, e17972 (2011).
pubmed: 21437233
pmcid: 3060099
Olson, S. W. et al. Asymptomatic autoantibodies associate with future anti-glomerular basement membrane disease. J. Am. Soc. Nephrol. 22, 1946–1952 (2011).
pubmed: 21868497
pmcid: 3279953
Cui, Z., Zhao, M. H., Segelmark, M. & Hellmark, T. Natural autoantibodies to myeloperoxidase, proteinase 3, and the glomerular basement membrane are present in normal individuals. Kidney Int. 78, 590–597 (2010).
pubmed: 20592714
Tan, D. S. et al. Thymic deletion and regulatory T cells prevent antimyeloperoxidase GN. J. Am. Soc. Nephrol. 24, 573–585 (2013).
pubmed: 23393320
pmcid: 3609139
Abdulahad, W. H. et al. Functional defect of circulating regulatory CD4+ T cells in patients with Wegener’s granulomatosis in remission. Arthritis Rheumatol. 56, 2080–2091 (2007).
Free, M. E. et al. Patients with antineutrophil cytoplasmic antibody-associated vasculitis have defective Treg cell function exacerbated by the presence of a suppression-resistant effector cell population. Arthritis Rheumatol. 65, 1922–1933 (2013).
Bunch, D. O. et al. Decreased CD5
pubmed: 23293123
pmcid: 3586963
Wilde, B. et al. Regulatory B cells in ANCA-associated vasculitis. Ann. Rheum. Dis. 72, 1416–1419 (2013).
pubmed: 23666929
Free, M. E. et al. Restricted myeloperoxidase epitopes drive the adaptive immune response in MPO-ANCA vasculitis. J. Autoimm. 106, 102306 (2020).
Ooi, J. D. et al. The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis. Proc. Natl Acad. Sci. USA 109, E2615–E2624 (2012). This study uses experimental models to demonstrate the role of MPO-specific CD4
pubmed: 22955884
Roth, A. J. et al. Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis. J. Clin. Invest. 123, 1773–1783 (2013).
pubmed: 23549081
pmcid: 3613913
Chang, J. et al. CD8
pubmed: 27288012
Falk, R. J., Becker, M., Terrell, R. & Jennette, J. C. Anti-myeloperoxidase autoantibodies react with native but not denatured myeloperoxidase. Clin. Exp. Immunol. 89, 274–278 (1992).
pubmed: 1379133
pmcid: 1554440
Bini, P. et al. Antineutrophil cytoplasmic autoantibodies in Wegener’s granulomatosis recognize conformational epitope(s) on proteinase 3. J. Immunol. 149, 1409–1415 (1992).
pubmed: 1380042
Audrain, M. A. et al. Anti-native and recombinant myeloperoxidase monoclonals and human autoantibodies. Clin. Exp. Immunol. 107, 127–134 (1997).
pubmed: 9010267
pmcid: 1904562
Nagai, M. et al. Serum levels of BAFF and APRIL in myeloperoxidase anti-neutrophil cytoplasmic autoantibody-associated renal vasculitis: association with disease activity. Nephron Clin. Pract. 118, c339–c345 (2011).
pubmed: 21293157
Holden, N. J. et al. ANCA-stimulated neutrophils release BLyS and promote B cell survival: a clinically relevant cellular process. Ann. Rheum. Dis. 70, 2229–2233 (2011).
pubmed: 21859691
Oleinika, K., Mauri, C. & Salama, A. D. Effector and regulatory B cells in immune-mediated kidney disease. Nat. Rev. Nephrol. 15, 11–26 (2019).
pubmed: 30443016
Steinmetz, O. M. et al. Analysis and classification of B-cell infiltrates in lupus and ANCA-associated nephritis. Kidney Int. 74, 448–457 (2008).
pubmed: 18528326
Kelley, J. M. et al. IgA and IgG antineutrophil cytoplasmic antibody engagement of Fc receptor genetic variants influences granulomatosis with polyangiitis. Proc. Natl Acad. Sci. USA 108, 20736–20741 (2011).
pubmed: 22147912
Jayne, D. R. et al. Severe pulmonary hemorrhage and systemic vasculitis in association with circulating anti-neutrophil cytoplasm antibodies of IgM class only. Clin. Nephrol. 32, 101–106 (1989).
pubmed: 2791359
Falk, R. J., Terrell, R. S., Charles, L. A. & Jennette, J. C. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc. Natl Acad. Sci. USA 87, 4115–4119 (1990). This study links ANCAs to the pathogenesis of AAV by demonstrating that ANCAs activate neutrophils in vitro.
pubmed: 2161532
Williams, J. M. 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, 661–669 (2003).
pubmed: 12595502
Hewins, P., Williams, J. M., Wakelam, M. J. & Savage, C. O. Activation of Syk in neutrophils by antineutrophil cytoplasm antibodies occurs via Fcγ receptors and CD18. J. Am. Soc. Nephrol. 15, 796–808 (2004).
pubmed: 14978183
Johnson, P. A., Alexander, H. D., McMillan, S. A. & Maxwell, A. P. Up-regulation of the granulocyte adhesion molecule Mac-1 by autoantibodies in autoimmune vasculitis. Clin. Exp. Immunol. 107, 513–519 (1997).
pubmed: 9067526
pmcid: 1904596
Kuligowski, M. P. et al. Antimyeloperoxidase antibodies rapidly induce alpha-4-integrin-dependent glomerular neutrophil adhesion. Blood 113, 6485–6494 (2009).
pubmed: 19383970
Tse, W. Y., Nash, G. B., Hewins, P., Savage, C. O. & Adu, D. ANCA-induced neutrophil F-actin polymerization: implications for microvascular inflammation. Kidney Int. 67, 130–139 (2005).
pubmed: 15610236
Jennette, J. C. & Nachman, P. H. ANCA glomerulonephritis and vasculitis. Clin. J. Am. Soc. Nephrol. 12, 1680–1691 (2017).
pubmed: 28842398
pmcid: 5628710
Hong, Y. et al. Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles. J. Am. Soc. Nephrol. 23, 49–62 (2012).
pubmed: 22052057
Xiao, H. et al. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J. Clin. Invest. 110, 955–963 (2002). A key study that uses experimental models to demonstrate the pathogenicity of anti-MPO antibodies in vivo.
pubmed: 12370273
pmcid: 151154
Bansal, P. J. & Tobin, M. C. Neonatal microscopic polyangiitis secondary to transfer of maternal myeloperoxidase-antineutrophil cytoplasmic antibody resulting in neonatal pulmonary hemorrhage and renal involvement. Ann. Allergy Asthma Immunol. 93, 398–401 (2004).
pubmed: 15521377
Xiao, H. et al. The role of neutrophils in the induction of glomerulonephritis by anti-myeloperoxidase antibodies. Am. J. Pathol. 167, 39–45 (2005).
pubmed: 15972950
pmcid: 1603451
Pfister, H. et al. Antineutrophil cytoplasmic autoantibodies against the murine homolog of proteinase 3 (Wegener autoantigen) are pathogenic in vivo. Blood 104, 1411–1418 (2004).
pubmed: 15150076
Little, M. A. et al. Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system. PLoS ONE 7, e28626 (2012).
pubmed: 22247758
pmcid: 3256135
Charles, L. A., Falk, R. J. & Jennette, J. C. Reactivity of antineutrophil cytoplasmic autoantibodies with mononuclear phagocytes. J. Leuk. Biol. 51, 65–68 (1992).
O’Brien, E. C. et al. Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1β secretion in response to anti-MPO antibodies. Sci. Rep. 5, 11888 (2015).
pubmed: 26149790
pmcid: 4493694
Peschel, A. et al. Autoantibodies to hLAMP-2 in ANCA-negative pauci-immune focal necrotizing GN. J. Am. Soc. Nephrol. 25, 455–463 (2014).
pubmed: 24203998
Espy, C. et al. Sialylation levels of anti-proteinase 3 antibodies are associated with the activity of granulomatosis with polyangiitis (Wegener’s). Arthritis Rheumatol. 63, 2105–2115 (2011).
Lardinois, O. M. et al. Immunoglobulins G from patients with ANCA-associated vasculitis are atypically glycosylated in both the Fc and Fab regions and the relation to disease activity. PLoS ONE 14, e0213215 (2019).
pubmed: 30818380
pmcid: 6395067
Ciavatta, D. J. et al. Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis. J. Clin. Invest. 120, 3209–3219 (2010).
pubmed: 20714105
pmcid: 2929711
Ohlsson, S. M. et al. Neutrophils from vasculitis patients exhibit an increased propensity for activation by anti-neutrophil cytoplasmic antibodies. Clin. Exp. Immunol. 176, 363–372 (2014).
pubmed: 24666336
pmcid: 4008980
Ohlsson, S. et al. Neutrophils from ANCA-associated vasculitis patients show an increased capacity to activate the complement system via the alternative pathway after ANCA stimulation. PLoS ONE 14, e0218272 (2019).
pubmed: 31216309
pmcid: 6583988
Summers, S. A. et al. Intrinsic renal cell and leukocyte-derived TLR4 aggravate experimental anti-MPO glomerulonephritis. Kidney Int. 78, 1263–1274 (2010).
pubmed: 20844472
Tadema, H. et al. Bacterial DNA motifs trigger ANCA production in ANCA-associated vasculitis in remission. Rheumatology 50, 689–696 (2011).
pubmed: 21149241
Holle, J. U. et al. Toll-like receptor TLR2 and TLR9 ligation triggers neutrophil activation in granulomatosis with polyangiitis. Rheumatology 52, 1183–1189 (2013).
pubmed: 23407387
Wang, C. et al. High mobility group box 1 contributes to anti-neutrophil cytoplasmic antibody-induced neutrophils activation through receptor for advanced glycation end products (RAGE) and Toll-like receptor 4. Arthritis Res. Ther. 17, 64 (2015).
pubmed: 25889374
pmcid: 4382936
Xiao, H. et al. C5a receptor (CD88) blockade protects against MPO-ANCA GN. J. Am. Soc. Nephrol. 25, 225–231 (2014).
pubmed: 24179165
Jayne, D. R. W. et al. Randomized trial of C5a receptor inhibitor avacopan in ANCA-associated vasculitis. J. Am. Soc. Nephrol. 28, 2756–2767 (2017).
pubmed: 28400446
pmcid: 5576933
Merkel, P. A. et al. A randomised, double-blind, active-controlled study of Avacopan in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Ann. Rheum. Dis. 79, 8 (2020).
Xiao, H., Schreiber, A., Heeringa, P., Falk, R. J. & Jennette, J. C. Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am. J. Pathol. 170, 52–64 (2007).
pubmed: 17200182
pmcid: 1762697
Huugen, D. et al. Inhibition of complement factor C5 protects against anti-myeloperoxidase antibody-mediated glomerulonephritis in mice. Kidney Int. 71, 646–654 (2007).
pubmed: 17299525
Hao, J., Meng, L. Q., Xu, P. C., Chen, M. & Zhao, M. H. p38MAPK, ERK and PI3K signaling pathways are involved in C5a-primed neutrophils for ANCA-mediated activation. PLoS ONE 7, e38317 (2012).
pubmed: 22675451
pmcid: 3365028
Dick, J. et al. C5a receptor 1 promotes autoimmunity, neutrophil dysfunction and injury in experimental anti-myeloperoxidase glomerulonephritis. Kidney Int. 93, 615–625 (2018).
pubmed: 29241626
Freeley, S. J. et al. Experimentally-induced anti-myeloperoxidase vasculitis does not require properdin, MASP-2 or bone marrow-derived C5. J. Pathol. 240, 61–71 (2016).
pubmed: 27235854
pmcid: 4996338
Gou, S. J., Yuan, J., Wang, C., Zhao, M. H. & Chen, M. Alternative complement pathway activation products in urine and kidneys of patients with ANCA-associated GN. Clin. J. Am. Soc. Nephrol. 8, 1884–1891 (2013).
pubmed: 24115193
pmcid: 3817906
Chen, M., Jayne, D. R. W. & Zhao, M. H. Complement in ANCA-associated vasculitis: mechanisms and implications for management. Nat. Rev. Nephrol. 13, 359–367 (2017).
pubmed: 28316335
Manenti, L. et al. Association of serum C3 concentration and histologic signs of thrombotic microangiopathy with outcomes among patients with ANCA-associated renal vasculitis. Clin. J. Am. Soc. Nephrol. 10, 2143–2151 (2015).
pubmed: 26542163
pmcid: 4670755
Augusto, J. F. et al. Low serum complement C3 levels at diagnosis of renal ANCA-associated vasculitis is associated with poor prognosis. PLoS ONE 11, e0158871 (2016).
pubmed: 27391243
pmcid: 4938207
Calderwood, J. W., Williams, J. M., Morgan, M. D., Nash, G. B. & Savage, C. O. ANCA induces β2 integrin and CXC chemokine-dependent neutrophil-endothelial cell interactions that mimic those of highly cytokine-activated endothelium. J. Leuk. Biol. 77, 33–43 (2005).
Little, M. A. et al. Antineutrophil cytoplasm antibodies directed against myeloperoxidase augment leukocyte-microvascular interactions in vivo. Blood 106, 2050–2058 (2005).
pubmed: 15933057
Nolan, S. L. et al. Mechanisms of ANCA-mediated leukocyte-endothelial cell interactions in vivo. J. Am. Soc. Nephrol. 19, 973–984 (2008).
pubmed: 18305123
pmcid: 2386723
Brouwer, E. et al. Predominance of IgG1 and IgG4 subclasses of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients with Wegener’s granulomatosis and clinically related disorders. Clin. Exp. Immunol. 83, 379–386 (1991).
pubmed: 1848489
pmcid: 1535341
Abdulahad, W. H. et al. Increased frequency of circulating IL-21 producing Th-cells in patients with granulomatosis with polyangiitis (GPA). Arthritis Res. Ther. 15, R70 (2013).
pubmed: 23799890
pmcid: 4060544
Abdulahad, W. H., Kallenberg, C. G., Limburg, P. C. & Stegeman, C. A. Urinary CD4+effector memory T cells reflect renal disease activity in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 60, 2830–2838 (2009).
Gephardt, G. N., Ahmad, M. & Tubbs, R. R. Pulmonary vasculitis (Wegener’s granulomatosis). Immunohistochemical study of T and B cell markers. Am. J. Med. 74, 700–704 (1983).
pubmed: 6601459
Weidner, S., Carl, M., Riess, R. & Rupprecht, H. D. Histologic analysis of renal leukocyte infiltration in antineutrophil cytoplasmic antibody-associated vasculitis: importance of monocyte and neutrophil infiltration in tissue damage. Arthritis Rheumatol. 50, 3651–3657 (2004).
O’Sullivan, K. M. et al. Renal participation of myeloperoxidase in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Kidney Int. 88, 1030–1046 (2015).
pubmed: 26176828
Ludviksson, B. R. et al. Active Wegener’s granulomatosis is associated with HLA-DR
pubmed: 9531324
Nogueira, E. et al. Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis. Nephrol. Dial. Transplant. 25, 2209–2217 (2010).
pubmed: 20100727
Csernok, E. et al. Cytokine profiles in Wegener’s granulomatosis: predominance of type 1 (Th1) in the granulomatous inflammation. Arthritis Rheumatol. 42, 742–750 (1999).
Chanouzas, D. et al. The host cellular immune response to cytomegalovirus targets the endothelium and is associated with increased arterial stiffness in ANCA-associated vasculitis. Arthritis Res. Ther. 20, 194 (2018).
pubmed: 30157919
pmcid: 6116544
Chanouzas, D. et al. Subclinical reactivation of cytomegalovirus drives CD4
pubmed: 30102389
McKinney, E. F. et al. A CD8
pubmed: 20400961
pmcid: 3504359
McKinney, E. F., Lee, J. C., Jayne, D. R., Lyons, P. A. & Smith, K. G. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature 523, 612–616 (2015).
pubmed: 26123020
pmcid: 4623162
Bajema, I. M., Hagen, E. C., de Heer, E., van der Woude, F. J. & Bruijn, J. A. Colocalization of ANCA-antigens and fibrinoid necrosis in ANCA-associated vasculitis. Kidney Int. 60, 2025–2030 (2001).
pubmed: 11703623
Gan, P. Y. et al. Biologicals targeting T helper cell subset differentiating cytokines are effective in the treatment of murine anti-myeloperoxidase glomerulonephritis. Kidney Int. 96, 1121–1133 (2019).
pubmed: 31443998
Rousselle, A., Kettritz, R. & Schreiber, A. Monocytes promote crescent formation in anti-myeloperoxidase antibody-induced glomerulonephritis. Am. J. Pathol. 187, 1908–1915 (2017).
pubmed: 28667835
Terrier, B. et al. Interleukin-25: a cytokine linking eosinophils and adaptive immunity in Churg-Strauss syndrome. Blood 116, 4523–4531 (2010).
pubmed: 20729468
Kiene, M. et al. Elevated interleukin-4 and interleukin-13 production by T cell lines from patients with Churg-Strauss syndrome. Arthritis Rheumatol. 44, 469–473 (2001).
Jakiela, B. et al. Increased production of IL-5 and dominant Th2-type response in airways of Churg-Strauss syndrome patients. Rheumatology 51, 1887–1893 (2012).
pubmed: 22772323
Wechsler, M. E. et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N. Engl. J. Med. 376, 1921–1932 (2017). A clinical trial that demonstrates that the anti-IL-5 therapy mepolizumab is an effective treatment for EGPA.
pubmed: 28514601
pmcid: 5548295
Biasci, D. et al. A blood-based prognostic biomarker in IBD. Gut 68, 1386–1395 (2019).
pubmed: 31030191
pmcid: 6691955
Jennette, J. C. et al. 2012 Revised International Chapel Hill consensus Conference Nomenclature of Vasculitides. Arthritis Rheumatol. 65, 1–11 (2013). A key classification paper that provides definitive definitions for each type of vasculitis.
Watts, R. A. & Robson, J. Introduction, epidemiology and classification of vasculitis. Best Pract. Res. Clin. Rheumatol. 32, 3–20 (2018).
pubmed: 30526896
Luqmani, R. A., Suppiah, R., Grayson, P. C., Merkel, P. A. & Watts, R. Nomenclature and classification of vasculitis - update on the ACR/EULAR Diagnosis and Classification of Vasculitis Study (DCVAS). Clin. Exp. Immunol. 164, 11–13 (2011).
pubmed: 21447123
pmcid: 3095857
Kariv, R., Sidi, Y. & Gur, H. Systemic vasculitis presenting as a tumorlike lesion. Four case reports and an analysis of 79 reported cases. Medicine 79, 349–359 (2000).
pubmed: 11144033
Jennette, J. C. & Falk, R. J. Small-vessel vasculitis. N. Engl. J. Med. 337, 1512–1523 (1997). This article reviews clinical and other aspects of small-vessel vasculitides, including AAVs.
pubmed: 9366584
Borie, R. & Crestani, B. Antineutrophil cytoplasmic antibody-associated lung fibrosis. Semin. Respir. Crit. Care Med. 39, 465–470 (2018).
pubmed: 30404113
Furuta, S. et al. Comparison of phenotype and outcome in microscopic polyangiitis between Europe and Japan. J. Rheumatol. 41, 325–333 (2014).
pubmed: 24429174
Suzuki, A. et al. Chest high-resolution CT findings of microscopic polyangiitis: a Japanese first nationwide prospective cohort study. Am. J. Roentgenol. 23, 1–11 (2019).
McAdoo, S. P. et al. Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients. Kidney Int. 92, 693–702 (2017).
pubmed: 28506760
pmcid: 5567410
Turner-Stokes, T. et al. Positive antineutrophil cytoplasmic antibody serology in patients with lupus nephritis is associated with distinct histopathologic features on renal biopsy. Kidney Int. 92, 1223–1231 (2017).
pubmed: 28750930
pmcid: 5652376
Anders, H. J. et al. MPO-ANCA-positive crescentic glomerulonephritis: a distinct entity of scleroderma renal disease? Am. J. Kidney Dis. 33, e3 (1999).
pubmed: 10196034
Quéméneur, T. et al. Systemic vasculitis during the course of systemic sclerosis: report of 12 cases and review of the literature. Medicine 92, 1–9 (2013).
pubmed: 23263715
pmcid: 5370746
Iudici, M. et al. Childhood- versus adult-onset ANCA-associated vasculitides: a nested, matched case-control study from the French Vasculitis Study Group Registry. Autoimmun. Rev. 17, 108–114 (2018).
pubmed: 29180123
Antonelou, M., Perea Ortega, L., Harvey, J. & Salama, A. D. Anti-myeloperoxidase antibody positivity in patients without primary systemic vasculitis. Clin. Exp. Rheumatol. 37, 86–89 (2019).
pubmed: 30767872
Berti, A. et al. Brief report: circulating cytokine profiles and antineutrophil cytoplasmic antibody specificity in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 70, 1114–1121 (2018).
pubmed: 29693324
pmcid: 6093207
Unizony, S. et al. Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Ann. Rheum. Dis. 75, 1166–1169 (2016).
pubmed: 26621483
Cornec, D., Cornec-Le Gall, E., Fervenza, F. C. & Specks, U. ANCA-associated vasculitis - clinical utility of using ANCA specificity to classify patients. Nat. Rev. Rheumatol. 12, 570–579 (2016).
pubmed: 27464484
Bossuyt, X. et al. Position paper: Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat. Rev. Rheumatol. 13, 683–692 (2017). Contemporary recommendations on ANCA testing methods and procedures in suspected AAV.
pubmed: 28905856
Venhoff, N. et al. Reconstitution of the peripheral B lymphocyte compartment in patients with ANCA-associated vasculitides treated with rituximab for relapsing or refractory disease. Autoimmunity 47, 401–408 (2014).
pubmed: 24798501
von Borstel, A. et al. CD27
O’Reilly, V. P. et al. Urinary soluble CD163 in active renal vasculitis. J. Am. Soc. Nephrol. 27, 2906–2916 (2016). This study identifies soluble urinary CD163 as a potential biomarker for renal flares of AAV.
pubmed: 26940094
pmcid: 5004645
Tedesco, M., Gallieni, M., Pellegata, F., Cozzolino, M. & Alberici, F. Update on ANCA-associated vasculitis: from biomarkers to therapy. J. Nephrol. 32, 871–882 (2019).
pubmed: 31301058
Dekkema, G. J. et al. Urinary and serum soluble CD25 complements urinary soluble CD163 to detect active renal anti-neutrophil cytoplasmic autoantibody-associated vasculitis: a cohort study. Nephrol. Dial. Transpl. 34, 234–242 (2019).
Ponte, C., Agueda, A. F. & Luqmani, R. A. Clinical features and structured clinical evaluation of vasculitis. Best. Pract. Res. Clin. Rheumatol. 32, 31–51 (2018).
pubmed: 30526897
Mukhtyar, C. et al. Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann. Rheum. Dis. 68, 1827–1832 (2009). An update of the BVAS, which is widely used in clinical trials to assess disease activity.
pubmed: 19054820
Hellmich, B. et al. EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann. Rheum. Dis. 66, 605–617 (2007).
pubmed: 17170053
Guillevin, L. et al. The five-factor score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine 90, 19–27 (2011).
pubmed: 21200183
Exley, A. R. et al. Development and initial validation of the vasculitis damage index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheumatol. 40, 371–380 (1997).
Merkel, P. A. et al. The OMERACT core set of outcome measures for use in clinical trials of ANCA-associated vasculitis. J. Rheumatol. 38, 1480–1486 (2011).
pubmed: 21724720
pmcid: 3645858
Morgan, M. D. et al. Increased incidence of cardiovascular events in patients with antineutrophil cytoplasmic antibody-associated vasculitides: a matched-pair cohort study. Arthritis Rheumatol. 60, 3493–3500 (2009).
Robson, J. et al. Damage in the ANCA-associated vasculitides: long-term data from the European Vasculitis Study Group (EUVAS) therapeutic trials. Ann. Rheum. Dis. 74, 177–184 (2015).
pubmed: 24243925
Emmi, G. et al. Thrombosis in vasculitis: from pathogenesis to treatment. Thromb. J. 13, 15 (2015).
pubmed: 25883536
pmcid: 4399148
Merkel, P. A. et al. Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener’s Clinical Occurrence of Thrombosis (WeCLOT) study. Ann. Intern. Med. 142, 620–626 (2005).
pubmed: 15838068
Whyte, A. F., Smith, W. B., Sinkar, S. N., Kette, F. E. & Hissaria, P. Clinical and laboratory characteristics of 19 patients with Churg-Strauss syndrome from a single South Australian centre. Intern. Med. J. 43, 784–790 (2013).
pubmed: 23611179
Mohammad, A. J. et al. Pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: the influence of ANCA subtype. J. Rheumatol. 44, 1458–1467 (2017).
pubmed: 28765242
Quinn, K. A. et al. Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis. Rheumatology 58, 2203–2211 (2019).
pubmed: 31199488
Churg, A. in Oxford Textbook of Vasculitis (eds Ball G. V., Fessler B. J., & Bridges S. L.) Ch. 9 101–108 (Oxford University Press, 2014).
Berden, A. E. et al. Histopathologic classification of ANCA-associated glomerulonephritis. J. Am. Soc. Nephrol. 21, 1628–1636 (2010). A classification system based on glomerular histopathology, which is associated with the outcome of renal disease in AAV.
pubmed: 20616173
Rahmattulla, C., Bruijn, J. A. & Bajema, I. M. Histopathological classification of antineutrophil cytoplasmic antibody-associated glomerulonephritis: an update. Curr. Opin. Nephrol. Hyperten. 23, 224–231 (2014).
Brix, S. R. et al. Development and validation of a renal risk score in ANCA-associated glomerulonephritis. Kidney Int. 94, 1177–1188 (2018).
pubmed: 30385041
Zhang, S., Yuan, D. & Tan, G. Neurological involvement in primary systemic vasculitis. Front. Neurol. 10, 430 (2019).
pubmed: 31105641
pmcid: 6498988
Flossmann, O. et al. Long-term patient survival in ANCA-associated vasculitis. Ann. Rheum. Dis. 70, 488–494 (2011).
pubmed: 21109517
Rhee, R. L. et al. Trends in long-term outcomes among patients with antineutrophil cytoplasmic antibody-associated vasculitis with renal disease. Arthritis Rheumatol. 68, 1711–1720 (2016).
pubmed: 26814428
pmcid: 4920688
Steinberg, A. W., Wechsler, M. E. & Fernandez Perez, E. R. Trends in antineutrophil cytoplasmic autoantibody-associated vasculitis-related mortality in the United States, 1999 to 2017. Ann. Intern. Med. 172, 160–163 (2020).
pubmed: 31590187
Scherlinger, M. et al. Worldwide trends in all-cause mortality of auto-immune systemic diseases between 2001 and 2014. Autoimmun. Rev. 19, 102531 (2020).
pubmed: 32234406
Hogan, S. L. et al. Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann. Intern. Med. 143, 621–631 (2005).
pubmed: 16263884
Gopaluni, S. et al. Effect of disease activity at three and six months after diagnosis on long-term outcomes in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 71, 784–791 (2019).
pubmed: 30418705
Walsh, M. et al. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N. Engl. J. Med. 382, 622–631 (2020). A clinical trial of induction therapies in severe AAV, which demonstrates that lower-dose glucocorticoids are non-inferior to standard doses and that routine use of plasma exchange as adjuvant provides no additional benefit.
pubmed: 32053298
pmcid: 7325726
Smith, R., Jayne, D. & Merkel, P. A randomized, controlled trial of rituximab versus azathioprine after induction of remission with rituximab for patients with ANCA-associated vasculitis and relapsing disease (abstract). Arthritis Rheumatol. 71 (Suppl. 10) (2019).
de Groot, K. et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann. Intern. Med. 150, 670–680 (2009).
pubmed: 19451574
Harper, L. et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann. Rheum. Dis. 71, 955–960 (2012).
pubmed: 22128076
Stone, J. H. et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N. Engl. J. Med. 363, 221–232 (2010). A clinical trial that demonstrates that rituximab is at least equivalent to cyclophosphamide in the induction of remission in AAV.
pubmed: 20647199
pmcid: 3137658
Specks, U. et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N. Engl. J. Med. 369, 417–427 (2013).
pubmed: 23902481
pmcid: 5953195
Jones, R. B. et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N. Engl. J. Med. 363, 211–220 (2010).
pubmed: 20647198
Pepper, R. J. et al. A novel glucocorticoid-free maintenance regimen for anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology 58, 260–268 (2019).
pubmed: 30239910
De Groot, K. et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 52, 2461–2469 (2005).
Jones, R. B. et al. Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial. Ann. Rheum. Dis. 78, 399–405 (2019).
pubmed: 30612116
Jayne, D. R. et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J. Am. Soc. Nephrol. 18, 2180–2188 (2007).
pubmed: 17582159
Jayne, D. R. et al. Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM 93, 433–439 (2000).
pubmed: 10874052
Guillevin, L. et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N. Engl. J. Med. 371, 1771–1780 (2014). A clinical trial demonstrating that rituximab is a viable treatment and superior to azathioprine in the maintenance of remission in AAV.
pubmed: 25372085
Karras, A. et al. Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis. Ann. Rheum. Dis. 76, 1662–1668 (2017).
pubmed: 28546260
Charles, P. et al. Long-term rituximab use to maintain remission of antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann. Intern. Med. https://doi.org/10.7326/M19-3827 (2020).
doi: 10.7326/M19-3827
pubmed: 32479166
Gopaluni, S. et al. Rituximab versus azathioprine as therapy for maintenance of remission for anti-neutrophil cytoplasm antibody-associated vasculitis (RITAZAREM): study protocol for a randomized controlled trial. Trials 18, 112 (2017).
pubmed: 28270229
pmcid: 5341185
Tieu, J. et al. Rituximab for maintenance of remission in ANCA-associated vasculitis: expert consensus guidelines. Rheumatology 59, e24–e32 (2020).
pubmed: 32096545
Charles, P. et al. Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2). Ann. Rheum. Dis. 77, 1143–1149 (2018).
pubmed: 29695500
Puéchal, X. et al. Adding azathioprine to remission-induction glucocorticoids for eosinophilic granulomatosis with polyangiitis (Churg-Strauss), microscopic polyangiitis, or polyarteritis nodosa without poor prognosis factors: a randomized, controlled trial. Arthritis Rheumatol. 69, 2175–2186 (2017).
pubmed: 28678392
Steinfeld, J. et al. Evaluation of clinical benefit from treatment with mepolizumab for patients with eosinophilic granulomatosis with polyangiitis. J. Allergy Clin. Immmunol. 143, 2170–2177 (2019).
Teixeira, V., Mohammad, A. J., Jones, R. B., Smith, R. & Jayne, D. Efficacy and safety of rituximab in the treatment of eosinophilic granulomatosis with polyangiitis. RMD Open 5, e000905 (2019).
pubmed: 31245051
pmcid: 6560673
Roberts, D. M. et al. Immunoglobulin G replacement for the treatment of infective complications of rituximab-associated hypogammaglobulinemia in autoimmune disease: a case series. J. Autoimmun. 57, 24–29 (2015).
pubmed: 25586449
De Sousa, E., Smith, R., Chaudhry, A., Willcocks, L. & Jayne, D. Venous thromboembolism with concurrent pulmonary haemorrhage in systemic vasculitis. Nephrol. Dial. Transplant. 27, 4357–4361 (2012).
pubmed: 22553370
Suppiah, R. et al. A model to predict cardiovascular events in patients with newly diagnosed Wegener’s granulomatosis and microscopic polyangiitis. Arthritis Care Res. 63, 588–596 (2011).
Westman, K. W., Bygren, P. G., Olsson, H., Ranstam, J. & Wieslander, J. Relapse rate, renal survival, and cancer morbidity in patients with Wegener’s granulomatosis or microscopic polyangiitis with renal involvement. J. Am. Soc. Nephrol. 9, 842–852 (1998).
pubmed: 9596082
Heijl, C. et al. Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials. Ann. Rheum. Dis. 70, 1415–1421 (2011).
pubmed: 21616914
van Daalen, E. E. et al. Effect of rituximab on malignancy risk in patients with ANCA-associated vasculitis. Ann. Rheum. Dis. 76, 1064–1069 (2017).
pubmed: 27899372
Buckley, L. & Humphrey, M. B. Glucocorticoid-induced osteoporosis. N. Engl. J. Med. 379, 2547–2556 (2018).
pubmed: 30586507
Martinez del Pero, M. et al. Long-term outcome of airway stenosis in granulomatosis with polyangiitis (Wegener granulomatosis): an observational study. JAMA Otolaryngol. Head Neck Surg. 140, 1038–1044 (2014).
pubmed: 25321076
Hruskova, Z. et al. Characteristics and outcomes of granulomatosis with polyangiitis (Wegener) and microscopic polyangiitis requiring renal replacement therapy: results from the European Renal Association-European Dialysis and Transplant Association Registry. Am. J. Kidney Dis. 66, 613–620 (2015).
pubmed: 25975963
Herlyn, K., Hellmich, B., Seo, P., Merkel, P. A. & The Vasculitis Clinical Research Consortium. Patient-reported outcome assessment in vasculitis may provide important data and a unique perspective. Arthritis Care Res. 62, 1639–1645 (2010).
Robson, J. C. et al. Patient perceptions of glucocorticoids in anti-neutrophil cytoplasmic antibody-associated vasculitis. Rheumatol. Int. 38, 675–682 (2018). A study reporting the effects of glucocorticoids in AAV, both positive and negative, from the patients’ perspective.
pubmed: 29124398
Miloslavsky, E. M. et al. Development of a Glucocorticoid Toxicity Index (GTI) using multicriteria decision analysis. Ann. Rheum. Dis. 76, 543–546 (2017).
pubmed: 27474764
Robson, J. C. et al. Validation of the ANCA-associated vasculitis patient-reported outcomes (AAV-PRO) questionnaire. Ann. Rheum. Dis. 77, 1157–1164 (2018). Validation study of an AAV-specific PRO measure.
pubmed: 29695498
pmcid: 7250143
Robson, J. C. et al. OMERACT endorsement of patient-reported outcome instruments in antineutrophil cytoplasmic antibody-associated vasculitis. J. Rheumatol. 44, 1529–1535 (2017).
pubmed: 28864650
pmcid: 5951181
O’Malley, L. et al. The longitudinal course of fatigue in antineutrophil cytoplasmic antibody-associated vasculitis. J. Rheumatol. 47, 572–579 (2020). This study defines the incidence and time course of fatigue, an important symptom for patients with AAV.
pubmed: 31263068
Hessels, A. C. et al. Leg muscle strength is reduced and is associated with physical quality of life in Antineutrophil cytoplasmic antibody-associated vasculitis. PLoS ONE 14, e0211895 (2019).
pubmed: 30716132
pmcid: 6361463
Harper, L. et al. Treatment of fatigue with physical activity and behavioural change support in vasculitis: study protocol for an open-label randomised controlled feasibility study. BMJ Open 8, e023769 (2018).
pubmed: 30377212
pmcid: 6224747
Moran, S. M. et al. Urinary soluble CD163 and monocyte chemoattractant protein-1 in the identification of subtle renal flare in anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrol. Dial. Transplant. 35, 283–291 (2020).
pubmed: 30380100
Pagnoux, C. et al. Treatment of systemic necrotizing vasculitides in patients aged sixty-five years or older: results of a multicenter, open-label, randomized controlled trial of corticosteroid and cyclophosphamide-based induction therapy. Arthritis Rheumatol. 67, 1117–1127 (2015).
pubmed: 25693055
Jones, R. B. et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial. Ann. Rheum. Dis. 74, 1178–1182 (2015).
pubmed: 25739829
Walsh, M. et al. Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int. 84, 397–402 (2013).
pubmed: 23615499
Merkel, P. A., Jayne, D. R., Wang, C., Hillson, J. & Bekker, P. Evaluation of the safety and efficacy of avacopan, a C5a receptor inhibitor, in patients with antineutrophil cytoplasmic antibody-associated vasculitis treated concomitantly with rituximab or cyclophosphamide/azathioprine: protocol for a randomized, double-blind, active-controlled, Phase 3 trial. JMIR Res. Protoc. 9, e16664 (2020).
pubmed: 32088663
pmcid: 7175182
Faurschou, M. et al. Brief report: long-term outcome of a randomized clinical trial comparing methotrexate to cyclophosphamide for remission induction in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 64, 3472–3477 (2012).
Jayne, D. et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N. Engl. J. Med. 349, 36–44 (2003).
pubmed: 12840090
Pagnoux, C. et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N. Engl. J. Med. 359, 2790–2803 (2008).
pubmed: 19109574
Puéchal, X. et al. Long-term outcomes among participants in the WEGENT trial of remission-maintenance therapy for granulomatosis with polyangiitis (Wegener’s) or microscopic polyangiitis. Arthritis Rheumatol. 68, 690–701 (2016).
pubmed: 26473755
Hiemstra, T. F. et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA 304, 2381–2388 (2010).
pubmed: 21060104
Terrier, B. et al. Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides. Ann. Rheum. Dis. 77, 1150–1156 (2018).
pubmed: 29724729
Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener’s granulomatosis. N. Engl. J. Med. 352, 351–361 (2005).
Metzler, C. et al. Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener’s granulomatosis. Rheumatology 46, 1087–1091 (2007).
pubmed: 17519271
Jayne, D. et al. Efficacy and safety of belimumab and azathioprine for maintenance of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled study. Arthritis Rheumatol. 71, 952–963 (2019).
pubmed: 30666823
pmcid: 6593987
Stegeman, C. A., Tervaert, J. W., de Jong, P. E., Kallenberg, C. G. & Dutch Co-Trimoxazole Wegener Study Group. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener’s granulomatosis. N. Engl. J. Med. 335, 16–20 (1996).
pubmed: 8637536
Ribi, C. et al. Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized, open-label study of seventy-two patients. Arthritis Rheumatol. 58, 586–594 (2008).
Puéchal, X. et al. Non-severe eosinophilic granulomatosis with polyangiitis: long-term outcomes after remission-induction trial. Rheumatology 58, 2107–2116 (2019).
pubmed: 31056661
Guillevin, L. et al. Lack of superiority of steroids plus plasma exchange to steroids alone in the treatment of polyarteritis nodosa and Churg-Strauss syndrome. A prospective, randomized trial in 78 patients. Arthritis Rheumatol. 35, 208–215 (1992).
Guillevin, L. et al. Corticosteroids plus pulse cyclophosphamide and plasma exchanges versus corticosteroids plus pulse cyclophosphamide alone in the treatment of polyarteritis nodosa and Churg-Strauss syndrome patients with factors predicting poor prognosis. A prospective, randomized trial in sixty-two patients. Arthritis Rheumatol. 38, 1638–1645 (1995).
Ma, T. K., McAdoo, S. P. & Tam, F. W. Targeting the tyrosine kinase signalling pathways for treatment of immune-mediated glomerulonephritis: from bench to bedside and beyond. Nephrol. Dial. Transpl. 32 (Suppl. 1), i129–i138 (2017).
Langford, C. A. et al. An open-label trial of abatacept (CTLA4-IG) in non-severe relapsing granulomatosis with polyangiitis (Wegener’s). Ann. Rheum. Dis. 73, 1376–1379 (2014).
pubmed: 24323392
Holdsworth, S. R., Gan, P. Y. & Kitching, A. R. Biologics for the treatment of autoimmune renal diseases. Nat. Rev. Nephrol. 12, 217–231 (2016).
pubmed: 26949177
Gan, P. Y. et al. Apoptotic cell-induced, antigen-specific immunoregulation to treat experimental antimyeloperoxidase GN. J. Am. Soc. Nephrol. 30, 1365–1374 (2019).
pubmed: 31337690
pmcid: 6683705
Bunch, D. O. et al. Gleaning relapse risk from B cell phenotype: decreased CD5
pubmed: 25934841
pmcid: 4534316
Ormerod, A. S. & Cook, M. C. Epidemiology of primary systemic vasculitis in the Australian Capital Territory and south-eastern New South Wales. Intern. Med. J. 38, 816–823 (2008).
pubmed: 18771432
Anderson, K., Klassen, J., Stewart, S. A. & Taylor-Gjevre, R. M. Does geographic location affect incidence of ANCA-associated renal vasculitis in northern Saskatchewan, Canada? Rheumatology 52, 1840–1844 (2013).
pubmed: 23838025
Reinhold-Keller, E., Herlyn, K., Wagner-Bastmeyer, R. & Gross, W. L. Stable incidence of primary systemic vasculitides over five years: results from the German vasculitis register. Arthritis Rheumatol. 53, 93–99 (2005).
Panagiotakis, S. H. et al. The epidemiology of primary systemic vasculitides involving small vessels in Crete (southern Greece): a comparison of older versus younger adult patients. Clin. Exp. Rheumatol. 27, 409–415 (2009).
pubmed: 19604432
Fujimoto, S. et al. Comparison of the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis between Japan and the UK. Rheumatology 50, 1916–1920 (2011).
pubmed: 21798892
Dadoniene, J., Kirdaite, G., Mackiewicz, Z., Rimkevicius, A. & Haugeberg, G. Incidence of primary systemic vasculitides in Vilnius: a university hospital population based study. Ann. Rheum. Dis. 64, 335–336 (2005).
pubmed: 15647446
pmcid: 1755373
Pamuk, O., Donmez, S. & Calayir, G. B. The incidences of anti-neutrophil cytoplasmic antibody-associated vasculitis in northeastern part of Turkey. Ann. Rheum. Dis. 72, 638–638 (2013).
Sánchez Torres, A. et al. Epidemiology of primary systemic vasculitis in a Latin America population [Spanish]. Rev. Chil. Reumatol. 21, 145–150 (2005).
Gonzalez-Gay, M. A., Garcia-Porrua, C., Guerrero, J., Rodriguez-Ledo, P. & Llorca, J. The epidemiology of the primary systemic vasculitides in northwest Spain: implications of the Chapel Hill Consensus Conference definitions. Arthritis Rheumatol. 49, 388–393 (2003).
Romero-Gomez, C. et al. Epidemiological study of primary systemic vasculitides among adults in southern Spain and review of the main epidemiological studies. Clin. Exp. Rheumatol. 33 (Suppl. 89), 11–18 (2015).
Mohammad, A. J., Jacobsson, L. T. H., Westman, K. W. A., Sturfelt, G. & Segelmark, M. Incidence and survival rates in Wegener’s granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and polyarteritis nodosa. Rheumatology 48, 1560–1565 (2009).
pubmed: 19797309
Zeft, A. S. & Schlesinger, M. K. H. Wegener’s granulomatosis and environmental factors in Western Montana. Rheumatol. Rep. https://doi.org/10.4081/rr.2010.e8 (2010).
doi: 10.4081/rr.2010.e8
Nesher, G., Ben-Chetrit, E., Mazal, B. & Breuer, G. S. The incidence of primary systemic vasculitis in Jerusalem: a 20-year hospital-based retrospective study. J. Rheumatol. 43, 1072–1077 (2016).
pubmed: 27084915
Damoiseaux, J. et al. An international survey on anti-neutrophil cytoplasmic antibodies (ANCA) testing in daily clinical practice. Clin. Chem. Lab. Med. 56, 1759–1770 (2018).
pubmed: 28710880
Damoiseaux, J. et al. Detection of antineutrophil cytoplasmic antibodies (ANCAs): a multicentre European Vasculitis Study Group (EUVAS) evaluation of the value of indirect immunofluorescence (IIF) versus antigen-specific immunoassays. Ann. Rheum. Dis. 76, 647–653 (2017).
pubmed: 27481830
Savige, J. et al. International consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies (ANCA). Am. J. Clin. Pathol. 111, 507–513 (1999).
pubmed: 10191771
Weiner, M. & Segelmark, M. The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies (ANCA). Autoimmun. Rev. 15, 978–982 (2016).
pubmed: 27481040
Zhao, M. H. et al. Autoantibodies against bactericidal/permeability-increasing protein in patients with cystic fibrosis. QJM 89, 259–265 (1996).
pubmed: 8733512
Choi, H. K., Lamprecht, P., Niles, J. L., Gross, W. L. & Merkel, P. A. Subacute bacterial endocarditis with positive cytoplasmic antineutrophil cytoplasmic antibodies and anti-proteinase 3 antibodies. Arthritis Rheumatol. 43, 226–231 (2000).
Mahr, A. et al. Brief report: prevalence of antineutrophil cytoplasmic antibodies in infective endocarditis. Arthritis Rheumatol. 66, 1672–1677 (2014).
pubmed: 24497495
Ying, C. M., Yao, D. T., Ding, H. H. & Yang, C. D. Infective endocarditis with antineutrophil cytoplasmic antibody: report of 13 cases and literature review. PLoS ONE 9, e89777 (2014).
pubmed: 24587028
pmcid: 3934949
Chen, M., Gao, Y., Guo, X. H. & Zhao, M. H. Propylthiouracil-induced antineutrophil cytoplasmic antibody-associated vasculitis. Nat. Rev. Nephrol. 8, 476–483 (2012).
pubmed: 22664738
Pendergraft, W. F. & Niles, J. L. Trojan horses: drug culprits associated with antineutrophil cytoplasmic autoantibody (ANCA) vasculitis. Curr. Opin. Rheumatol. 26, 42–49 (2014).
pubmed: 24276086
Grau, R. G. Drug-induced vasculitis: new insights and a changing lineup of suspects. Curr. Rheumatol. Rep. 17, 71 (2015).
pubmed: 26503355
Lee, E. et al. Inactivation of peroxidases of rat bone marrow by repeated administration of propylthiouracil is accompanied by a change in the heme structure. Biochem. Pharmacol. 37, 2151–2153 (1988).
pubmed: 2837228
Nakazawa, D. et al. Abnormal conformation and impaired degradation of propylthiouracil-induced neutrophil extracellular traps: implications of disordered neutrophil extracellular traps in a rat model of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 64, 3779–3787 (2012).
Lood, C. & Hughes, G. C. Neutrophil extracellular traps as a potential source of autoantigen in cocaine-associated autoimmunity. Rheumatology 56, 638–643 (2017).
pubmed: 27354687