Anti-neutrophil cytoplasmic antibody (ANCA) may target proteinase 3 (PR3) or myeloperoxidase (MPO). Although a few patients with vasculitis have both MPO- and PR3-ANCA, the details of their clinical characteristics are not known. The objective of this study was to analyze the characteristics of patients with dual MPO- and PR3-ANCA-positive vasculitis. The medical records of patients with ANCA and vasculitis confirmed by biopsy were reviewed. The age at diagnosis, sex, and data on organ involvement of the kidney, lung, upper airways, skin, nervous system, and gastrointestinal tract were collected. Clinical variables were analyzed according to ANCA specificity. Of 85 patients with ANCA and vasculitis included in this study, 67 (78.8%) had MPO-ANCA, 10 (11.8%) had PR3-ANCA, and 8 (9.4%) had both MPO- and PR3-ANCA. Patients with MPO− PR3 + ANCA-associated vasculitis (AAV) were younger at diagnosis (median, 54.4 years; p < 0.05) than patients with MPO + PR3− AAV (67.0 years) or dual-ANCA AAV (MPO + PR3 + , 68.5 years). The initial glomerular filtration rate in patients with MPO + PR3− AAV (22.0 ml/min) was significantly lower than that in patients with MPO− PR3 + AAV (108.6 ml/min, p < 0.05), but was not different from that in dual-ANCA AAV patients (16.5 ml/min). Upper airway involvement also differed with ANCA type (MPO+ PR3− , 35.8% vs. MPO− PR3 + , 70.0% vs. MPO + PR3+ , 75.0%, p < 0.05). The involvement of other organs did not differ according to ANCA type. Age at diagnosis, kidney involvement, and upper airway involvement were associated with ANCA type. Patients with dual-ANCA-positive vasculitis had considerably more kidney dysfunction than patients with MPO− PR3+ AAV. They also had more upper airway involvement than patients with MPO+ PR3− AAV.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF et al (2013) 2012 revised international Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum 65:1–11
Mahr A, Guillevin L, Poissonnet M, Ayme S (2004) 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 Rheum 51:92–99
Watts RA, Mahr A, Mohammad AJ, Gatenby P, Basu N, Flores-Suárez LF (2015) Classification, epidemiology and clinical subgrouping of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Nephrol Dial Transpl 30(Suppl. 1):14–22
Groh M, Pagnoux C, Baldini C, Bel E, Bottero P, Cottin V, Dalhoff K et al (2015) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) consensus task force recommendations for evaluation and management. Eur J Intern Med 26:545–553
Falk RJ, Jennette JC (1998) Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med 318:1651–1657
Ludemann J, Utecht B, Gross WL (1990) Anti-neutrophil cytoplasm antibodies in Wegener’s granulomatosis recognize an elastinolytic enzyme. J Exp Med 171:357–362
Jenne DE, Tschopp J, Ludemann J, Utecht B, Gross WL (1990) Wegener’s autoantigen decoded. Nature 346:520
Cornec D, Cornec-Le Gall E, Fervenza FC, Specks U (2016) ANCA-associated vasculitis—clinical utility of using ANCA specificity to classify patients. Nature Rev Rheumatol 12:570–579
Hagen EC, Daha MR, Hermans J, Andrassy K, Csernok E, Gaskin G, Lesavre P et al (1998) Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. EC/BCR project for ANCA assay standardization. Kidney Int 53:743–753
Shah S, Havill J, Rahman MH, Geetha D (2016) A historical study of American patients with anti-neutrophil cytoplasmic antibody negative pauci-immune glomerulonephritis. Clin Rheumatol 35:953–960
Franssen C, Gans R, Kallenberg C, Hageluken C, Hoorntje S (1998) Disease spectrum of patients with antineutrophil cytoplasmic autoantibodies of defined specificity: distinct differences between patients with anti-proteinase 3 and anti-myeloperoxidase autoantibodies. J Intern Med 244:209–216
Pearce FA, Craven A, Merkel PA, Luqmani RA, Watts RA (2017) Global ethnic and geographic differences in the clinical presentations of anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology (Oxford) 56:1962–1969
Chou J, Randall K, Gatenby P (2015) Clinical outcomes of patients with dual positivity for proteinase 3 and myeloperoxidase specific antineutrophil cytoplasmic antibodies. J Clin Cell Immunol 6:3. https://doi.org/10.4172/2155-9899.1000335
Mukhtyar C, Lee R, Brown D, Carruthers D, Dasgupta B, Dubey S (2009) Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann Rheum Dis 68:1827–1832
Li C, Zhou ML, Liang DD, Wang JJ, Yang J, Zeng CH et al (2017) Treatment and clinicopathological characteristics of lupus nephritis with anti-neutrophil cytoplasmic antibody positivity: a case-control study. BMJ Open 7:e015668
Murakami M, Shimane K, Takahashi H, Tomiyama J, Nagashima M (2013) ANCA-associated vasculitis with dual ANCA positivity in coexistence with mixed connective tissue disease. Mod Rheumatol 23:156–161
Ueda H, Ishimura E, Yunoki T, Tsuchida T, Matsumoto N, Jono S et al (2005) Cimetidine-induced tubulointerstitial nephritis with both MPO-ANCA and PR3-ANCA. Clin Exp Nephrol 9:332–334
Ferraz-Amaro I, Herrero MJ, Jurado A, Diaz-Gonzalez F (2004) Dual positivity for cytoplasmic and perinuclear anti-neutrophil antibodies in a patient with Henoch-Schonlein purpura. Clin Exp Rheumatol 22:233–234
Tiliakos AM, Tiliakos NA (2008) Dual ANCA positivity in subacute bacterial endocarditis. J Clin Rheumatol 14:38–40
de Joode AA, Sanders JS, Stegeman CA (2013) Renal survival in proteinase 3 and myeloperoxidase ANCA-associated systemic vasculitis. Clin J Am Soc Nephrol 8:1709–1717
Mohammad AJ, Segelmark M (2014) A population-based study showing better renal prognosis for proteinase 3 antineutrophil cytoplasmic antibody (ANCA)-associated nephritis versus myeloperoxidase ANCA-associated nephritis. J Rheumatol 41:1366–1373
Sada KE, Yamamura M, Harigai M, Fujii T, Dobashi H, Takasaki Y, Ito S et al (2014) Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study. Arthritis Res Ther 16:R101
Comarmond C, Crestani B, Tazi A, Hervier B, Adam-Marchand S, Nunes H, Cohen-Aubart F et al (2014) Pulmonary fibrosis in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: a series of 49 patients and review of the literature. Medicine (Baltimore) 93:340–349
Unizony S, Villarreal M, Miloslavsky EM, Lu N, Merkel PA, Spiera R, Seo P et al (2016) Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Ann Rheum Dis 75:1166–1169
Ikeda S, Arita M, Misaki K, Kashiwagi Y, Ito Y, Yamada H et al (2015) Comparative investigation of respiratory tract involvement in granulomatosis with polyangiitis between PR3-ANCA positive and MPO-ANCA positive cases: a retrospective cohort study. BMC Pulm Med 15:78
Falk RJ, Terrell RS, Charles LA, Jennette JC (1990) Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci USA 87:4115–4119
Xiao H, Heeringa P, Hu P, Liu Z, Zhao M, Aratani Y, Maeda N (2002) Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest 110:955–963
Glasner C, van Timmeren MM, Stobernack T, Omansen TF, Raangs EC, Rossen JW, de Goffau MC et al (2015) Low anti-staphylococcal IgG responses in granulomatosis with polyangiitis patients despite long-term Staphylococcus aureus exposure. Sci Rep 5:8188
Brockmann H, Schwarting A, Kriegsmann J, Petrow P, Gaumann A, Müller KM et al (2002) Proteinase-3 as the major autoantigen of c-ANCA is strongly expressed in lung tissue of patients with Wegener’s granulomatosis. Arthritis Res 4:220–225
Schwarting A, Hagen D, Odenthal M, Brockmann H, Dienes HP, Wandel E et al (2000) Proteinase-3 mRNA expressed by glomerular epithelial cells correlates with crescent formation in Wegener’s granulomatosis. Kidney Int 57:2412–2422
O’Sullivan KM, Lo CY, Summers SA, Elgass KD, McMillan PJ, Longano A et al (2015) Renal participation of myeloperoxidase in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Kidney Int 88:1030–1046
Miloslavsky EM, Lu N, Unizony S, Choi HK, Merkel PA, Seo P et al (2016) Myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)–positive and ANCA-negative patients with granulomatosis with polyangiitis (Wegener’s). Arthritis Rheumatol 68:2945–2952
Schirmer JH, Wright M, Herrmann K, Laudien M, Nolle B, Reinhold-Keller E et al (2016) Myeloperoxidase–antineutrophil cytoplasmic antibody (ANCA)–positive granulomatosis with polyangiitis (Wegener’s) is a clinically distinct subset of ANCA-associated vasculitis. Arthritis Rheumatol 68:2953–2956
Chen M, Yu F, Zhang Y, Zou WZ, Zhao MH, Wang HY (2005) Characteristics of Chinese patients with Wegener’s granulomatosis with anti-myeloperoxidase autoantibodies. Kidney Int 68:2225–2229
Ono N, Niiro H, Ueda A, Sawabe T, Nishizaka H, Furugo I et al (2015) Characteristics of MPO-ANCA-positive granulomatosis with polyangiitis: a retrospective multi-center study in Japan. Rheumatol Int 35:555–559
Lionaki S, Blyth ER, Hogan SL, Hu Y, Senior BA, Jennette CE et al (2012) Classification of antineutrophil cytoplasmic autoantibody vasculitides: the role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis. Arthritis Rheum 64:3452–3462
Mukhtyar C, Guillevin L, Cid MC, Dasgupta B, de Groot K, Gross W et al (2009) EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 68:310–317
Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T (2016) EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 75:1583–1594
Mahr A, Specks U, Jayne D (2019) Subclassifying ANCA-Associated vasculitis: a unifying view of disease spectrum. Rheumatology. https://doi.org/10.1093/rheumatology/kez148(Epub ahead of print)
Mahr A, Katsahian S, Varet H, Guillevin L, Hagen EC, Höglund P et al (2013) Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis. Ann Rheum Dis 72:1003–1010
Emejuaiwe N (2019) Treatment strategies in ANCA-associated vasculitis. Curr Rheumatol Rep 21(7):33
Miloslavsky EM, Specks U, Merkel PA, Seo P, Spiera R, Langford CA et al (2013) Clinical outcomes of remission induction therapy for severe antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 65:2441–2449
There was no support from any external editing agency.
This research was supported by the Basic Science Research Program through the National Research Foundation funded by the Ministry of Education of Korea (NRF-2018R1D1A1B07043681).
Conflict of interest
The authors declare that they have no conflicts of interests.
This study was approved by Chungnam National University Hospital Institutional Review Board (2017-1-31/2017-01-023) and Chungbuk National University Hospital Institutional Review Board (2019-4-25/CBNUH 2017-04-001) and informed consent was waived by each ethics committees. This study was conducted in accordance with the Declaration of Helsinki.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Kim, S.M., Choi, SY., Kim, S.Y. et al. Clinical characteristics of patients with vasculitis positive for anti-neutrophil cytoplasmic antibody targeting both proteinase 3 and myeloperoxidase: a retrospective study. Rheumatol Int 39, 1919–1926 (2019). https://doi.org/10.1007/s00296-019-04447-w
- Antibodies, antineutrophil cytoplasmic
- Systemic vasculitis
- Anti-neutrophil cytoplasmic antibody-associated vasculitis
- Microscopic polyangiitis
- Granulomatosis with polyangiitis