Subscribe to RSS
DOI: 10.1055/s-0038-1669914
Antineutrophil Cytoplasmic Antibody–Associated Lung Fibrosis
Publication History
Publication Date:
07 November 2018 (online)
![](https://www.thieme-connect.de/media/srccm/201804/lookinside/thumbnails/10-1055-s-0038-1669914_01391-1.jpg)
Abstract
Pulmonary fibrosis is observed in a substantial number of patients with ANCA-associated vasculitis (AAV), 15% in a recent German series, and may be more frequent in Asian populations. ANCA are usually of anti-MPO specificity and microscopic polyangiitis is the most frequent vasculitis. Pulmonary fibrosis may increase the risk of death in patients with AAV. Treatment for AAV in patients with lung fibrosis should follow the international guidelines for vasculitis. The role of anti-fibrotic drugs (pirfenidone, nintedanib) in this condition is still unknown. Pulmonary fibrosis precedes the diagnosis of AAV or is diagnosed concomitantly in most of the cases. Interestingly, 4% to 35% of patients with pulmonary fibrosis are ANCA-positive, but only 7% to 23% of the patients with pulmonary fibrosis and anti-MPO will develop AAV during follow-up. ANCA positivity may be detected in idiopathic or non idiopathic pulmonary fibrosis. In the absence of vasculitis, the detection of ANCA does not influence the diagnostic work-up of patients with lung fibrosis. If an Idiopathic Pulmonary Fibrosis diagnosis is considered, an anti-fibrotic therapy should be considered, according to local and international guidelines.
-
References
- 1 Raghu G, Collard HR, Egan JJ. , et al; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011; 183 (06) 788-824
- 2 Travis WD, Hoffman GS, Leavitt RY, Pass HI, Fauci AS. Surgical pathology of the lung in Wegener's granulomatosis. Review of 87 open lung biopsies from 67 patients. Am J Surg Pathol 1991; 15 (04) 315-333
- 3 Lederer DJ, Martinez FJ. Idiopathic pulmonary fibrosis. N Engl J Med 2018; 378 (19) 1811-1823
- 4 Molyneaux PL, Willis-Owen SAG, Cox MJ. , et al. Host-microbial interactions in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2017; 195 (12) 1640-1650
- 5 Selman M, López-Otín C, Pardo A. Age-driven developmental drift in the pathogenesis of idiopathic pulmonary fibrosis. Eur Respir J 2016; 48 (02) 538-552
- 6 Birnbaum J, Danoff S, Askin FB, Stone JH. Microscopic polyangiitis presenting as a “pulmonary-muscle” syndrome: is subclinical alveolar hemorrhage the mechanism of pulmonary fibrosis?. Arthritis Rheum 2007; 56 (06) 2065-2071
- 7 Kay JM, Edwards FR. Ultrastructure of the alveolar-capillary wall in mitral stenosis. J Pathol 1973; 111 (04) 239-245
- 8 Le Clainche L, Le Bourgeois M, Fauroux B. , et al. Long-term outcome of idiopathic pulmonary hemosiderosis in children. Medicine (Baltimore) 2000; 79 (05) 318-326
- 9 Chintagari NR, Jana S, Alayash AI. Oxidized ferric and ferryl forms of hemoglobin trigger mitochondrial dysfunction and injury in alveolar type I cells. Am J Respir Cell Mol Biol 2016; 55 (02) 288-298
- 10 Comarmond C, Crestani B, Tazi A. , et al. Pulmonary fibrosis in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: a series of 49 patients and review of the literature. Medicine (Baltimore) 2014; 93 (24) 340-349
- 11 Foulon G, Delaval P, Valeyre D. , et al. ANCA-associated lung fibrosis: analysis of 17 patients. Respir Med 2008; 102 (10) 1392-1398
- 12 Guilpain P, Chéreau C, Goulvestre C. , et al. The oxidation induced by antimyeloperoxidase antibodies triggers fibrosis in microscopic polyangiitis. Eur Respir J 2011; 37 (06) 1503-1513
- 13 Foucher P, Heeringa P, Petersen AH. , et al. Antimyeloperoxidase-associated lung disease. An experimental model. Am J Respir Crit Care Med 1999; 160 (03) 987-994
- 14 Lucattelli M, Bartalesi B, Cavarra E. , et al. Is neutrophil elastase the missing link between emphysema and fibrosis? Evidence from two mouse models. Respir Res 2005; 6: 83
- 15 Meyer KC, Raghu G, Baughman RP. , et al; American Thoracic Society Committee on BAL in Interstitial Lung Disease. An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. Am J Respir Crit Care Med 2012; 185 (09) 1004-1014
- 16 Turner-Warwick M, Doniach D. Auto-antibody studies in interstitial pulmonary fibrosis. BMJ 1965; 1 (5439): 886-891
- 17 Turner-Warwick M, Parkes WR. Circulating rheumatoid and antinuclear factors in asbestos workers. BMJ 1970; 3 (5721): 492-495
- 18 Soutar CA, Turner-Warwick M, Parkes WR. Circulating antinuclear antibody and rheumatoid factor in coal pneumoconiosis. BMJ 1974; 3 (5924): 145-147
- 19 Holgate ST, Haslam P, Turner-Warwick M. The significance of antinuclear and DNA antibodies in cryptogenic fibrosing alveolitis. Thorax 1983; 38 (01) 67-70
- 20 Kang BH, Park JK, Roh JH. , et al. Clinical significance of serum autoantibodies in idiopathic interstitial pneumonia. J Korean Med Sci 2013; 28 (05) 731-737
- 21 Lee JS, Kim EJ, Lynch KL. , et al. Prevalence and clinical significance of circulating autoantibodies in idiopathic pulmonary fibrosis. Respir Med 2013; 107 (02) 249-255
- 22 Hoyne GF, Elliott H, Mutsaers SE, Prêle CM. Idiopathic pulmonary fibrosis and a role for autoimmunity. Immunol Cell Biol 2017; 95 (07) 577-583
- 23 Herazo-Maya JD, Noth I, Duncan SR. , et al. Peripheral blood mononuclear cell gene expression profiles predict poor outcome in idiopathic pulmonary fibrosis. Sci Transl Med 2013; 5 (205) 205ra136
- 24 Herazo-Maya JD, Sun J, Molyneaux PL. , et al. Validation of a 52-gene risk profile for outcome prediction in patients with idiopathic pulmonary fibrosis: an international, multicentre, cohort study. Lancet Respir Med 2017; 5 (11) 857-868
- 25 Marchal-Sommé J, Uzunhan Y, Marchand-Adam S. , et al. Cutting edge: nonproliferating mature immune cells form a novel type of organized lymphoid structure in idiopathic pulmonary fibrosis. J Immunol 2006; 176 (10) 5735-5739
- 26 Marchal-Sommé J, Uzunhan Y, Marchand-Adam S. , et al. Dendritic cells accumulate in human fibrotic interstitial lung disease. Am J Respir Crit Care Med 2007; 176 (10) 1007-1014
- 27 Schiller HB, Mayr CH, Leuschner G. , et al. Deep proteome profiling reveals common prevalence of MZB1-positive plasma B cells in human lung and skin fibrosis. Am J Respir Crit Care Med 2017; 196 (10) 1298-1310
- 28 Feghali-Bostwick CA, Tsai CG, Valentine VG. , et al. Cellular and humoral autoreactivity in idiopathic pulmonary fibrosis. J Immunol 2007; 179 (04) 2592-2599
- 29 Groot Kormelink T, Pardo A, Knipping K. , et al. Immunoglobulin free light chains are increased in hypersensitivity pneumonitis and idiopathic pulmonary fibrosis. PLoS One 2011; 6 (09) e25392
- 30 Kotsianidis I, Nakou E, Bouchliou I. , et al. Global impairment of CD4+CD25+FOXP3+ regulatory T cells in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009; 179 (12) 1121-1130
- 31 Gereke M, Jung S, Buer J, Bruder D. Alveolar type II epithelial cells present antigen to CD4(+) T cells and induce Foxp3(+) regulatory T cells. Am J Respir Crit Care Med 2009; 179 (05) 344-355
- 32 Dall'Aglio PP, Pesci A, Bertorelli G, Brianti E, Scarpa S. Study of immune complexes in bronchoalveolar lavage fluids. Respiration 1988; 54 (Suppl. 01) 36-41
- 33 Dobashi N, Fujita J, Murota M. , et al. Elevation of anti-cytokeratin 18 antibody and circulating cytokeratin 18: anti-cytokeratin 18 antibody immune complexes in sera of patients with idiopathic pulmonary fibrosis. Lung 2000; 178 (03) 171-179
- 34 Kahloon RA, Xue J, Bhargava A. , et al. Patients with idiopathic pulmonary fibrosis with antibodies to heat shock protein 70 have poor prognoses. Am J Respir Crit Care Med 2013; 187 (07) 768-775
- 35 Wallace WA, Roberts SN, Caldwell H. , et al. Circulating antibodies to lung protein(s) in patients with cryptogenic fibrosing alveolitis. Thorax 1994; 49 (03) 218-224
- 36 Wallace WA, Schofield JA, Lamb D, Howie SE. Localisation of a pulmonary autoantigen in cryptogenic fibrosing alveolitis. Thorax 1994; 49 (11) 1139-1145
- 37 Dobashi N, Fujita J, Ohtsuki Y. , et al. Detection of anti-cytokeratin 8 antibody in the serum of patients with cryptogenic fibrosing alveolitis and pulmonary fibrosis associated with collagen vascular disorders. Thorax 1998; 53 (11) 969-974
- 38 Fujita J, Dobashi N, Ohtsuki Y. , et al. Elevation of anti-cytokeratin 19 antibody in sera of the patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with collagen vascular disorders. Lung 1999; 177 (05) 311-319
- 39 Yang Y, Fujita J, Bandoh S. , et al. Detection of antivimentin antibody in sera of patients with idiopathic pulmonary fibrosis and non-specific interstitial pneumonia. Clin Exp Immunol 2002; 128 (01) 169-174
- 40 Kurosu K, Takiguchi Y, Okada O. , et al. Identification of annexin 1 as a novel autoantigen in acute exacerbation of idiopathic pulmonary fibrosis. J Immunol 2008; 181 (01) 756-767
- 41 Fahim A, Chong MC, Crooks MG, Hart SP. Idiopathic pulmonary fibrosis is associated with circulating antiepithelial antibodies. Lung 2012; 190 (04) 451-458
- 42 Beltramo G, Thabut G, Peron N. , et al. Anti-parietal cell autoimmunity is associated with an accelerated decline of lung function in IPF patients. Respir Med 2018; 135: 15-21
- 43 Taillé C, Grootenboer-Mignot S, Boursier C. , et al. Identification of periplakin as a new target for autoreactivity in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011; 183 (06) 759-766
- 44 Watad A, Bragazzi NL, Adawi M. , et al. Autoimmunity in the elderly: insights from basic science and clinics - a mini-review. Gerontology 2017; 63 (06) 515-523
- 45 Borie R, Kannengiesser C, Sicre de Fontbrune F, Gouya L, Nathan N, Crestani B. Management of suspected monogenic lung fibrosis in a specialised centre. Eur Respir Rev 2017; 26 (144) xx-xx
- 46 Pagnoux C. Updates in ANCA-associated vasculitis. Eur J Rheumatol 2016; 3 (03) 122-133
- 47 Hoffman TW, van Moorsel CHM, Borie R, Crestani B. Pulmonary phenotypes associated with genetic variation in telomere-related genes. Curr Opin Pulm Med 2018; 24 (03) 269-280
- 48 Borie R, Tabèze L, Thabut G. , et al. Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis. Eur Respir J 2016; 48 (06) 1721-1731
- 49 Juge P-A, Borie R, Kannengiesser C. , et al; FREX consortium. Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis. Eur Respir J 2017; 49 (05) 1602314
- 50 Borie R, Kannengiesser C, Sicre de Fontbrune F. , et al. Pneumocystosis revealing immunodeficiency secondary to TERC mutation. Eur Respir J 2017; 50 (05) 1701443
- 51 Arulkumaran N, Periselneris N, Gaskin G. , et al. Interstitial lung disease and ANCA-associated vasculitis: a retrospective observational cohort study. Rheumatology (Oxford) 2011; 50 (11) 2035-2043
- 52 Schirmer JH, Wright MN, Herrmann K. , et al. Myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-positive granulomatosis with polyangiitis (Wegener's) is a clinically distinct subset of ANCA-associated vasculitis: a retrospective analysis of 315 patients from a German Vasculitis Referral Center. Arthritis Rheumatol 2016; 68 (12) 2953-2963
- 53 Schirmer JH, Wright MN, Vonthein R. , et al. Clinical presentation and long-term outcome of 144 patients with microscopic polyangiitis in a monocentric German cohort. Rheumatology (Oxford) 2016; 55 (01) 71-79
- 54 Tzelepis GE, Kokosi M, Tzioufas A. , et al. Prevalence and outcome of pulmonary fibrosis in microscopic polyangiitis. Eur Respir J 2010; 36 (01) 116-121
- 55 Huang H, Wang YX, Jiang CG. , et al. A retrospective study of microscopic polyangiitis patients presenting with pulmonary fibrosis in China. BMC Pulm Med 2014; 14: 8
- 56 Furuta S, Chaudhry AN, Hamano Y. , et al. Comparison of phenotype and outcome in microscopic polyangiitis between Europe and Japan. J Rheumatol 2014; 41 (02) 325-333
- 57 Fischer A, Antoniou KM, Brown KK. , et al; “ERS/ATS Task Force on Undifferentiated Forms of CTD-ILD”. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J 2015; 46 (04) 976-987
- 58 Kono M, Nakamura Y, Enomoto N. , et al. Usual interstitial pneumonia preceding collagen vascular disease: a retrospective case control study of patients initially diagnosed with idiopathic pulmonary fibrosis. PLoS One 2014; 9 (04) e94775
- 59 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 (01) e000058
- 60 Nozu T, Kondo M, Suzuki K, Tamaoki J, Nagai A. A comparison of the clinical features of ANCA-positive and ANCA-negative idiopathic pulmonary fibrosis patients. Respiration 2009; 77 (04) 407-415
- 61 Hozumi H, Enomoto N, Oyama Y. , et al. Clinical implication of proteinase-3-antineutrophil cytoplasmic antibody in patients with idiopathic interstitial pneumonias. Lung 2016; 194 (02) 235-242
- 62 Raghu G, Anstrom KJ, King Jr TE, Lasky JA, Martinez FJ. ; Idiopathic Pulmonary Fibrosis Clinical Research Network. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med 2012; 366 (21) 1968-1977
- 63 Ando M, Miyazaki E, Ishii T. , et al. Incidence of myeloperoxidase anti-neutrophil cytoplasmic antibody positivity and microscopic polyangiitis in the course of idiopathic pulmonary fibrosis. Respir Med 2013; 107 (04) 608-615
- 64 Hosoda C, Baba T, Hagiwara E. , et al. Clinical features of usual interstitial pneumonia with anti-neutrophil cytoplasmic antibody in comparison with idiopathic pulmonary fibrosis. Respirology 2016; 21 (05) 920-926
- 65 Cambridge G, Williams M, Leaker B, Corbett M, Smith CR. Anti-myeloperoxidase antibodies in patients with rheumatoid arthritis: prevalence, clinical correlates, and IgG subclass. Ann Rheum Dis 1994; 53 (01) 24-29
- 66 Raghu G, Rochwerg B, Zhang Y. , et al; American Thoracic Society; European Respiratory society; Japanese Respiratory Society; Latin American Thoracic Association. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med 2015; 192 (02) e3-e19
- 67 Cottin V, Crestani B, Cadranel J. , et al. French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis - 2017 update. Full-length version. Rev Mal Respir 2017; 34 (08) 900-968
- 68 Liu Y, Jesus AA, Marrero B. , et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med 2014; 371 (06) 507-518
- 69 Picard C, Thouvenin G, Kannengiesser C. , et al. Severe pulmonary fibrosis as the first manifestation of interferonopathy (TMEM173 mutation). Chest 2016; 150 (03) e65-e71
- 70 Seo J, Kang J-A, Suh DI. , et al. Tofacitinib relieves symptoms of stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy caused by 2 de novo variants in TMEM173. J Allergy Clin Immunol 2017; 139 (04) 1396-1399.e12
- 71 Frémond M-L, Rodero MP, Jeremiah N. , et al. Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in 3 children. J Allergy Clin Immunol 2016; 138 (06) 1752-1755
- 72 Watkin LB, Jessen B, Wiszniewski W. , et al; Baylor-Hopkins Center for Mendelian Genomics. COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis. Nat Genet 2015; 47 (06) 654-660
- 73 Volpi S, Tsui J, Mariani M. , et al. Type I interferon pathway activation in COPA syndrome. Clin Immunol 2018; 187: 33-36
- 74 Vece TJ, Watkin LB, Nicholas S. , et al. Copa syndrome: a novel autosomal dominant immune dysregulatory disease. J Clin Immunol 2016; 36 (04) 377-387
- 75 Tsui JL, Estrada OA, Deng Z. , et al. Analysis of pulmonary features and treatment approaches in the COPA syndrome. ERJ Open Res 2018; 4 (02) xx-xx
- 76 Noorelahi R, Perez G, Otero HJ. Imaging findings of Copa syndrome in a 12-year-old boy. Pediatr Radiol 2018; 48 (02) 279-282