MPO-ANCA positive interstitial pneumonia: Current knowledge and future perspectives

Main Article Content

Masashi Bando
Sakae Homma
Masayoshi Harigai


ANCA-associated vasculitis (AAV), anti-neutrophil cytoplasmic antibody (ANCA), idiopathic interstitial pneumonias (IIPs), interstitial pneumonia (IP), microscopic polyangiitis (MPA), myeloperoxidase (MPO)


Although interstitial pneumonia is an important respiratory manifestation in microscopic polyangiitis (MPA), no studies have examined the detailed pathogenesis of interstitial pneumonia during the clinical course of MPA. In addition, it is considered that MPA develops at a certain incidence rate from myeloperoxidase (MPO)- antineutrophil cytoplasmic antibody (ANCA) positive interstitial pneumonia. However, there is a lack of consensus among pulmonologist and rheumatologist regarding whether MPO-ANCA positive interstitial pneumonia, which does not accompany other organ damage related to ANCA-associated vasculitis (AAV) other than interstitial pneumonia, should be included in AAV.

In this review article, the clinical questions regarding MPO-ANCA positive interstitial pneumonia have been set, and evidence to date and problems to be solved in future are outlined.


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1 Alba MA, Flores-Suárez LF, Henderson AG, Xiao H, Hu P, Nachman PH, et al. Interstitial lung disease in ANCA vasculitis. Autoimmunity Reviews 2017;16:722-729.
2 Katsumata Y, Kawaguchi Y, Yamanaka H. Interstitial lung disease with ANCA-associated vasculitis. Clin Med Insights Circ Respir Pulm Med 2015;9:51-56.
3 Schirmer JH, Wright MN, Vonthein R, Herrmann K, Nölle B, Both M, et al. Clinical presentation and long-term outcome of 144 patients with microscopic polyangiitis in a monocentric German cohort. Rheumatology 2016;55:71-79.
4 Sacoto G, Boukhlal S, Specks U, Flores-Suárez LF, Cornec D. Lung involvement in ANCA-associated vasculitis. Presse Med 2020;49:104039.
5 Karras A. Microscopic polyangiitis: new insights into pathogenesis, clinical features and therapy. Semi Respir Crit Care Med 2018;39:459-464.
6 Ozaki S, Atsumi T, Hayashi T, Ishizu A, Kobayashi S, Kumagai S, et al. Severity-based treatment for Japanese patients with MPO-ANCA-associated vasculitis: the JMAAV study. Mod Rheumatol 2012;22:394-404.
7 Harigai M, Bando M, Takasaki T, Fujimoto A, Homma S. Questionnaire survey on interdisciplinary cooperation and MPO-ANCA positive interstitial pneumonia in AAV. Report of in the Ministry of Health, Labour, and Welfare, the Study Group on Diffuse Pulmonary Disorders, Scientific Research/Research on Intractable Diseases in the FY2019. 2020 [Article in Japanese].
8 Arimura Y, Minoshima S, Tanaka U, Fujii A, Kobayashi M, Nakabayashi K, et al. Pulmonary involvement in patients with myeloperoxidase specific-antineutrophil cytoplasmic antibody. Rheumatoid 1995;35:46-55 [Article in Japanese].
9 Sada K, Yamamura M, Harigai M, Fujii T, Dobashi H, Takasaki Y, et al. Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study. Arthritis Res Ther 2014;16:R101.
10 Hirayama K, Kobayashi M, Usui J, Arimura Y, Sugiyama H, Nitta K, et al. Pulmonary involvements of anti-neutrophil cytoplasmic autoantibody-associated renal vasculitis in Japan. Nephrol Dial Transplant 2015;30 Suppl 1:i83-93.
11 Tzelepis GE, Kokosi M, Tzioufas A, Toya SP, Boki KA, Zormpala A, et al. Prevalence and outcome of pulmonary fibrosis in microscopic polyangiitis. Eur Respir J 2010;36:116-121.
12 Arulkumaran N, Periselneris N, Gaskin G, Strickland N, Ind PW, Pusey CD, et al. Interstitial lung disease and ANCA-associated vasculitis: a retrospective observational cohort study. Rheumatology 2011;50:2035-2043.
13 Comarmond C, Crestani B, Tazi A, Hervier B, Adam-Marchand S, Nunes H, et al. Pulmonary fibrosis in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: a series of 49 patients and review of the literature. Medicine 2014;93:340-349.
14 Flores-Suárez LF, Ruiz N, Saldarriaga Rivera LM, PensadoL. Reduced survival in microscopic polyangiitis patients with pulmonary fibrosis in a respiratory referral centre. Clin Rheumatol 2015;34:1653-1654.
15 Fernandez Casares M, Gonzalez A, Fielli M, Caputo F, Bottinelli Y, Zamboni M. Microscopic polyangiitis associated with pulmonary fibrosis. Clin Rheumatol 2015;34:1273-1277.
16 Mohammad AJ, Mortensen KH, Babar J, Smith R, Jones RB, Nakagomi D, et al. Pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: The influence of ANCA subtype. J Rheumatol 2017;44:1458-1467.
17 Suzuki A, Sakamoto S, Kurosaki A, Kurihara Y, Satoh K, Usui Y, et al. Chest high-resolution CT findings of microscopic polyangiitis: A Japanese first nationalwide prospective cohort study. AJR Am J Roentgenol. 2019;213:104-114.
18 Maillet T, Goletto T, Beltramo G, Dupuy H, Jouneau S, Borie R, et al. Usual interstitial pneumonia in ANCA-associated vasculitis: A poor prognostic factor. J Autoimmun 2020;106: 102338.
19 Hozumi H, Kono M, Hasegawa H, Yasui H, Suzuki Y, Karayama M, et al. Clinical significance of interstitial lung disease and its acute exacerbation in microscopic polyangiitis. Chest 2021;
20 Homma S, Matsushita H, Nakata K. Pulmonary fibrosis in myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitides. Respirology 2004;9:190-196.
21 Tanaka T, Otani K, Egashira R, Kashima Y, Taniguchi H, Kondoh Y, et al. Interstitial pneumonia associated with MPO-ANCA: clinicopathological features of nine patients. Respir Med 2012;106:1765-1770.
22 Ando M, Miyazaki E, Ishii T, Mukai Y, Yamasue M, Fujisaki H, et al. Incidence of myeloperoxidase anti-neutrophil cytoplasmic antibody positivity and microscopic polyangitis in the course of idiopathic pulmonary fibrosis. Respir Med 2013;107:608-15.
23 Kagiyama N, Takayanagi N, Kanauchi T, Ishiguro T, Yanagisawa T, Sugita Y. Antineutrophil cytoplasmic antibody-positive conversion and microscopic polyangiitis development in patients with idiopathic pulmonary fibrosis. BMJ Open Respir Res 2015;2:e000058.
24 Hosoda C, Baba T, Hagiwara E, Ito H, Matsuo N, Kitamura H, et al. Clinical features of usual interstitial pneumonia with anti-neutrophil cytoplasmic antibody in comparison with idiopathic pulmonary fibrosis. Respirology 2016;21:920-926.
25 Hozumi H, Oyama Y, Yasui H, Suzuki Y, Kono M, Karayama M, et al. Clinical significance of myeloperoxidase-anti-neutrophil cytoplasmic antibody in idiopathic interstitial pneumonias. PLoS One 2018;13:e0199659.
26 Liu GY, Ventura IB, Achtar-Zadeh N, Elicker BM, Jones KD, Wolters PJ, et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in North American patients with idiopathic pulmonary fibrosis. Chest 2019;156:715-723.
27 Baqir M, Yi EE, Colby TV, Cox CW, Ryu JH, Specks U. Radiologic and pathologic characteristics of myeloperoxidase-antineutrophil cytoplasmic antibody-associated interstitial lung disease: a retrospective analysis. Sarcoidosis Vasc Diffuse Lung Dis 2019;36:195-201.
28 Little MA, Smyth L, Salama AD, Mukherjee S, Smith J, Haskard D, et al. Experimental autoimmune vasculitis: an animal model of anti-neutrophil cytoplasmic autoantibody-associated systemic vasculitis. Am J Pathol 2009;174:1212-1220.
29 Csernok E. Anti-neutrophil cytoplasmic antibodies and pathogenesis of small vessel vasculitides. Autoimmun Rev 2003;2:158-164.
30 Kessenbrock K, Krumbholz M, Schönermarck U, Back W, Gross WL, Werb Z, et al. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med 2009;15:623-625.
31 Nakazawa D, Tomaru U, Suzuki A, Masuda S, Hasegawa R, Kobayashi T, et al. Abnormal conformation and impaired degradation of propylthiouracil-induced neutrophil extracellular traps: implications of disorderd neutrophil extracellular traps in a rat model of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2012;64:3779-87.
32 Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science 2004;303:1532-5.
33 Chrysanthopoulou A, Mitroulis I, Apostolidou E, Arelaki S, Mikroulis D, Konstantinidis T, et al. Neutrophil extracellular traps promote differenciation and function of fibroblasts. J Pathol 2014;233:294-307.
34 Mukherjee M, Thomas SR, Radford K, Dvorkin-Gheva A, Davydchenko S, Kjarsgaard M, et al. Sputum ANCA in serum ANCA-negative eosinophilic granulomatosis with polyangiitis. Am J Respir Crit Care Med 2019;199:158-170.
35 Shaw M, Collins BF, Ho LA, Raghu G. Rheumatoid arthritis-associated lung disease. Eur Respir Rev 2015;24:1-16.
36 Namba N, Kawasaki A, Sada KE, Hirano F, Kobayashi S, Yamada H, et al. Association of MUC5B promoter polymorphism with interstitial lung disease in myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis. Ann Rheum Dis. 2019;78:1144-1146.
37 Kawasaki A, Namba N, Sada KE, Hirano F, Kobayashi S, Nagasaka K, et al. Association of TERT and DSP variants with microscopic polyangiitis and myeloperoxidase-ANCA positive vasculitis in a Japanese population: a genetic association study. Arthritis Res Ther. 2020;22:246.
38 Hebisawa A, Kuramochi S, Ogura T, Kawabata Y. Pathology of chronic interstitial pneumonia of MPO-ANCA serepositive cases. Jpn J Chest Dis 2008;67:210-219 [Article in Japanese].
39 Harigai M, Nagasaka K, Amano K, Bando M, Dobashi H, Kawakami T, et al. 2017 Clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of ANCA-associated vasculitis. Mod Rheumatol 2019;29:20-30.
40 Japanese Respiratory Society’s Committee formulating diagnosis and treatment guideline for diffuse lung diseases. Clinical diagnostic and treatment guidance for idiopathic interstitial pneumonias. Tokyo: Nankodo; 2016 [Article in Japanese].
41 Homma S, Bando M, Azuma A, Sakamoto S, Sugino K, Ishii Y, et al. Japanese guideline for the treatment of idiopathic pulmonary fibrosis. Respir Investig 2018;56:268-91.
42 Bossuyt X, Cohen Tervaert JW, Arimura Y, Blockmans D, Flores-Suárez LF, Guillevin L, et al. Position paper: Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol 2017;13:683-692.
43 Kinder BW, Collard HR, Koth L, Daikh DI, Wolters PJ, Elicker B, et al. Idiopathic nonspecific interstitial pneumonia: lung manifestation of undifferentiated connective disease? Am J Respir Crit Care Med 2007;176:691-697.
44 Fischer A, West SG, Swigris JJ, Brown KK, du Bois RM. Connective tissue disease-associated interstitial lung disease: a call for clarification. Chest 2010;138:251-256.
45 Vij R, Noth I, Strek ME. Autoimmune-featured interstitial lung disease: a distinct entity. Chest 2011;140:1292-1299.
46 Fischer A, Antoniou KM, Brown KK, Cadranel J, Corte TJ, du Bois RM, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J 2015;46:976-987.
47 Sambataro G, Sambataro D, Torrisi SE, Vancheri A, Pavone M, Rosso R, et al. State of the art in interstitial pneumonia with autoimmune features: a systemic review on retrospective studies and suggestions for further advances. Eur Respir Rev 2018;27:170139.
48 Fujimoto S, Watts RA, Kobayashi S, Suzuki K, Jayne DR, Scott DG, et al. Comparison of the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis between Japan and the UK. Rheumatology 2011;50:1916-1920.
49 Furuta S, Chaudhry AN, Hamano Y, Fujimoto S, Nagafuchi H, Makino H, et al. Comparison of phenotype and outcome in microscopic polyangiitis between Europe and Japan. J Rheumatol 2014;41:325-333.
50 Furuta S, Chaudhry AN, Arimura Y, Dobashi H, Fujimoto S, Homma S, et al. Comparison of the phenotype and outcome of granulomatosis with polyangiitis between UK and Japanese cohorts. J Rheumatol 2017;44:216-222.

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