Phenotypic clusters and survival analyses in interstitial pneumonia with myositis-specific autoantibodies

Main Article Content

Yihua Li
Yali Fan
Yuanying Wang
Shuqiao Yang
Xuqin Du
Qiao Ye

Keywords

myositis, autoantibody, cluster analysis, interstitial pneumonia, prognosis

Abstract

Background: Interstitial pneumonia (IP) is one of the common pulmonary complications of idiopathic inflammatory myopathy (IIM), among which myositis-specific autoantibodies (MSAs) are specific for diagnosing and predicting the prognosis of IIM.


Objectives: The study aimed to explore the phenotypic clusters and prognosis of patients with IP and MSA (MSA-IP).


Methods: A total of 178 patients with MSA-IP were prospectively enrolled for analysis. Serum MSAs were detected using Western blotting. Radiological patterns of IP were determined according to the classification of idiopathic IPs. Clusters of patients with MSA-IP were identified using cluster analysis. Predictors for acute/subacute onset, therapeutic response, IP progression and survival were also analyzed.


Results: Patients with MSA-IP were classified into four distinct clusters. Cluster 1 were the elderly with chronic onset, nearly normal oxygenation and good survival. Cluster 2 had dyspnea on exertion and nonspecific IP pattern, with moderate survival. Patients in cluster 3 had chronic onset and were prone to IP progression (OR 2.885). Cluster 4 had multi-systemic involvements, positive anti--melanoma differentiation associated gene 5 antibody, and were prone to acute/subacute onset (OR 3.538) and IP progression (OR 5.472), with poor survival. Corticosteroids combined immunosuppressants showed therapeutic response in MSA-IP (OR 4.303) and had a protective effect on IP progression (OR 0.136).


Conclusions: Four clusters of the patients with MSA-IP suggested the distinct clinical, radiological and prognostic features.

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References

1. Vij R ,Strek M E. Diagnosis and treatment of connective tissue disease-associated interstitial lung disease. Chest 2013; 143(3):814-824.
2. Fischer A, Antoniou K M ,Brown K K et al. An official European Respiratory Society/American Thoracic Society research statement: Interstitial pneumonia with autoimmune features. Eur Respir J 2015; 46(4):976-987.
3. Koo S M ,Uh S T. Treatment of connective tissue disease-associated interstitial lung disease: The pulmonologist's point of view. Korean J Intern Med 2017; 32(4):600-610.
4. Fischer A, West S G, Swigris J J, Brown K K ,du Bois R M. Connective tissue disease-associated interstitial lung disease: A call for clarification. Chest 2010; 138(2):251-256.
5. Le Goff B, Cherin P ,Cantagrel A et al. Pneumomediastinum in interstitial lung disease associated with dermatomyositis and polymyositis. Arthritis Rheum 2009; 61(1):108-118.
6. Bohan A ,Peter J B. Polymyositis and dermatomyositis (second of two parts). N Engl J Med 1975; 292(8):403-407.
7. Morisset J, Johnson C, Rich E, Collard H R ,Lee J S. Management of Myositis-Related interstitial lung disease. Chest 2016; 150(5):1118-1128.
8. Labirua A ,Lundberg I E. Interstitial lung disease and idiopathic inflammatory myopathies: Progress and pitfalls. Curr Opin Rheumatol 2010; 22(6):633-638.
9. Mimori T, Nakashima R ,Hosono Y. Interstitial lung disease in myositis: Clinical subsets, biomarkers, and treatment. Curr Rheumatol Rep 2012; 14(3):264-274.
10. Fathi M ,Lundberg I E. Interstitial lung disease in polymyositis and dermatomyositis. Curr Opin Rheumatol 2005; 17(6):701-706.
11. Fathi M, Vikgren J ,Boijsen M et al. Interstitial lung disease in polymyositis and dermatomyositis: Longitudinal evaluation by pulmonary function and radiology. Arthritis Rheum 2008; 59(5):677-685.
12. Marie I, Hachulla E ,Cherin P et al. Interstitial lung disease in polymyositis and dermatomyositis. Arthritis Rheum 2002; 47(6):614-622.
13. Chen I J, Jan W Y ,Lin C W et al. Interstitial lung disease in polymyositis and dermatomyositis. Clin Rheumatol 2009; 28(6):639-646.
14. Richards T J, Eggebeen A ,Gibson K et al. Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum 2009; 60(7):2183-2192.
15. Tieu J, Lundberg I E ,Limaye V. Idiopathic inflammatory myositis. Best Pract Res Clin Rheumatol 2016; 30(1):149-168.
16. Fidler L, Doubelt I, Kandel S, Fisher J H, Mittoo S ,Shapera S. Screening for myositis antibodies in idiopathic interstitial lung disease. Lung 2019; 197(3):277-284.
17. Ghirardello A, Zampieri S ,Tarricone E et al. Clinical implications of autoantibody screening in patients with autoimmune myositis. Autoimmunity 2006; 39(3):217-221.
18. Graham J, Bauer V I ,Newton C A et al. Myositis-specific antibodies identify a distinct interstitial pneumonia with autoimmune features phenotype. Eur Respir J 2020;
19. Tanizawa K, Handa T ,Nakashima R et al. The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies. Respir Med 2017; 127(57-64.
20. Jablonski R, Bhorade S, Strek M E ,Dematte J. Recognition and management of myositis-associated rapidly progressive interstitial lung disease. Chest 2020;
21. van de Velden M, D'Enza A I ,Palumbo F. Cluster correspondence analysis. Psychometrika 2017; 82(1):158-185.
22. Szodoray P, Hajas A ,Kardos L et al. Distinct phenotypes in mixed connective tissue disease: Subgroups and survival. Lupus 2012; 21(13):1412-1422.
23. Travis W D, Costabel U ,Hansell D M et al. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013; 188(6):733-748.
24. Lundberg I E, Tjarnlund A ,Bottai M et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis 2017; 76(12):1955-1964.
25. Wanger J, Clausen J L ,Coates A et al. Standardisation of the measurement of lung volumes. Eur Respir J 2005; 26(3):511-522.
26. Galiè N, Humbert M ,Vachiery J L et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: The joint task force for the diagnosis and treatment of pulmonary hypertension of the european society of cardiology (ESC) and the european respiratory society (ERS): Endorsed by: Association for european paediatric and congenital cardiology (AEPC), international society for heart and lung transplantation (ISHLT). Eur Heart J 2016; 37(1):67-119.
27. Eaden J A, Barber C M, Renshaw S A, Chaudhuri N ,Bianchi S M. Real world experience of response to pirfenidone in patients with idiopathic pulmonary fibrosis: A two centre retrospective study. Sarcoidosis Vasc Diffuse Lung Dis 2020; 37(2):218-224.
28. George P M, Spagnolo P ,Kreuter M et al. Progressive fibrosing interstitial lung disease: Clinical uncertainties, consensus recommendations, and research priorities. Lancet Respir Med 2020; 8(9):925-934.
29. Hervier B, Devilliers H ,Stanciu R et al. Hierarchical cluster and survival analyses of antisynthetase syndrome: Phenotype and outcome are correlated with anti-tRNA synthetase antibody specificity. Autoimmun Rev 2012; 12(2):210-217.
30. Mariampillai K, Granger B ,Amelin D et al. Development of a new classification system for idiopathic inflammatory myopathies based on clinical manifestations and Myositis-Specific autoantibodies. Jama Neurol 2018; 75(12):1528-1537.
31. Hamaguchi Y, Fujimoto M ,Matsushita T et al. Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: Heterogeneity within the syndrome. Plos One 2013; 8(4):e60442.
32. Watanabe K, Handa T ,Tanizawa K et al. Detection of antisynthetase syndrome in patients with idiopathic interstitial pneumonias. Respir Med 2011; 105(8):1238-1247.
33. Andersson H, Aaløkken T M ,Günther A et al. Pulmonary involvement in the antisynthetase syndrome: A comparative cross-sectional study. J Rheumatol 2016; 43(6):1107-1113.
34. Shi J, Li S ,Yang H et al. Clinical profiles and prognosis of patients with distinct antisynthetase autoantibodies. J Rheumatol 2017; 44(7):1051-1057.
35. Smith M, Dalurzo M, Panse P, Parish J ,Leslie K. Usual interstitial pneumonia-pattern fibrosis in surgical lung biopsies. Clinical, radiological and histopathological clues to aetiology. J Clin Pathol 2013; 66(10):896-903.
36. Park J H, Kim D S ,Park I N et al. Prognosis of fibrotic interstitial pneumonia: Idiopathic versus collagen vascular disease-related subtypes. Am J Respir Crit Care Med 2007; 175(7):705-711.
37. Moghadam-Kia S, Oddis C V, Sato S, Kuwana M ,Aggarwal R. Anti-Melanoma Differentiation-Associated gene 5 is associated with rapidly progressive lung disease and poor survival in US patients with amyopathic and myopathic dermatomyositis. Arthritis Care Res (Hoboken) 2016; 68(5):689-694.
38. Motegi S I, Sekiguchi A ,Toki S et al. Clinical features and poor prognostic factors of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with rapid progressive interstitial lung disease. Eur J Dermatol 2019; 29(5):511-517.
39. Cottin V, Hirani N A ,Hotchkin D L et al. Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev 2018; 27(150):
40. Cottin V. Treatment of progressive fibrosing interstitial lung diseases: A milestone in the management of interstitial lung diseases. Eur Respir Rev 2019; 28(153):
41. Flaherty K R, Brown K K ,Wells A U et al. Design of the PF-ILD trial: A double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease. BMJ Open Respir Res 2017; 4(1):e212.