Abstract
Objectives
Interstitial lung disease (ILD) is a common extra-muscular manifestation of anti-synthetase syndrome (ASS) and the main cause of morbidity and mortality in patients with ASS. Data on prognostic factors in these patients are lacking.
Methods
A total of 69 patients with ILD and positivity for at least one of the following autoantibodies were included: anti-Jo-1, anti-PL7, anti-PL12, and anti-EJ. Relevant clinical characteristics were registered. According to the changes in the extent of abnormalities at the follow-up on high-resolution computed tomography (HRCT), three groups were defined: the regression, stability, and deterioration groups. Univariate analysis was performed to evaluate possible prognostic factors and multivariate analysis by logistic regression was then applied to determine the independent prognostic factors in ASS-ILD.
Results
The cohort comprised 69 patients positive for anti-synthetase antibodies, i.e., 30 for anti-Jo-1, 16 for anti-EJ, 13 for anti-PL7, and 10 for anti-PL12. The mean length of follow-up was 15 months. Sex, age at diagnosis, fever at presentation, and counts of CD3+CD4+ cells were significantly different among the three groups. According to the multivariate analysis, fever at presentation, lower counts of CD3+CD4+ cells, and a pattern of usual interstitial pneumonia were the three independent risk factors for poor outcomes of ASS-ILD.
Conclusions
At the onset of ASS, some clinical features and HRCT pattern of ILD may suggest an unfavorable outcome of lung involvement on HRCT, even with routine therapy. These factors may contribute to the high long-term mortality of ASS.
Key Points
• Evaluation of lung involvement on HRCT is important in the follow-up of patients with interstitial lung disease related to anti-synthetase syndrome (ASS-ILD).
• The interstitial lung disease related to ASS responds to the treatment variably.
• Some clinical and imaging characteristics are associated with poor prognosis in patients with ASS-ILD, including fever at diagnosis, a lower serum CD3 + /CD4 + level, and a UIP pattern.
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Abbreviations
- AIP:
-
Acute interstitial pneumonia pattern
- ANA:
-
Anti-nuclear antibody
- ASS:
-
Anti-synthetase syndrome
- CI:
-
Confidence interval
- CK:
-
Creatine kinase
- CRP:
-
C-reactive protein
- CTDs:
-
Connective tissue diseases
- DLCO:
-
Diffusion capacity of the lung for carbon monoxide
- ESR:
-
The erythrocyte sedimentation rate
- FEV1:
-
Forced expiratory volume
- FVC:
-
Forced vital capacity
- GGO:
-
Ground glass opacities
- HRCT:
-
High-resolution computed tomography
- ILD:
-
Interstitial lung disease
- NSIP:
-
Nonspecific interstitial pneumonia
- OP:
-
Organizing pneumonia
- OR:
-
Odds ratio
- PFT:
-
Pulmonary function test
- RF:
-
Rheumatoid factor
- UIP:
-
Usual interstitial pneumonia
- VC:
-
Vital capacity
References
Nishikai M, Reichlin M (1980) Heterogeneity of precipitating antibodies in polymyositis and dermatomyositis. Characterization of the Jo-1 antibody system. Arthritis Rheum 23:881–888
Pinal-Fernandez I, Casal-Dominguez M, Huapaya JA et al (2017) A longitudinal cohort study of the anti-synthetase syndrome: increased severity of interstitial lung disease in black patients and patients with anti-PL7 and anti-PL12 autoantibodies. Rheumatology (Oxford) 56:999–1007
Shi J, Li S, Yang H et al (2017) Clinical profiles and prognosis of patients with distinct antisynthetase autoantibodies. J Rheumatol 44:1051–1057
Hervier B, Devilliers H, Stanciu R et al (2012) Hierarchical cluster and survival analyses of antisynthetase syndrome: phenotype and outcome are correlated with anti-tRNA synthetase antibody specificity. Autoimmun Rev 12:210–217
Hamaguchi Y, Fujimoto M, Matsushita T et al (2013) Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: heterogeneity within the syndrome. PLoS One 8:e60442
Arsura EL, Greenberg AS (1988) Adverse impact of interstitial pulmonary fibrosis on prognosis in polymyositis and dermatomyositis. Semin Arthritis Rheum 18:29–37
Love LA, Leff RL, Fraser DD et al (1991) A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine (Baltimore) 70:360–374
Mejía M, Herrera-Bringas D, Pérez-Román DI et al (2017) Interstitial lung disease and myositis-specific and associated autoantibodies: clinical manifestations, survival and the performance of the new ATS/ERS criteria for interstitial pneumonia with autoimmune features (IPAF). Respir Med 123:79–86
Marie I, Josse S, Decaux O et al (2012) Comparison of long-term outcome between anti-Jo1- and anti-PL7/PL12 positive patients with antisynthetase syndrome. Autoimmun Rev 11:739–745
Solomon J, Swigris JJ, Brown KK (2011) Myositis-related interstitial lung disease and antisynthetase syndrome. J Bras Pneumol 37:100–109
Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (second of two parts). N Engl J Med 292:403–407
Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292:344–347
Raghu G, Collard HR, Egan JJ et al (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183:788–824
Travis WD, Costabel U, Hansell DM et al (2013) 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 188:733–748
Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J (2008) Fleischner Society: glossary of terms for thoracic imaging. Radiology 246:697–722
Akira M, Inoue Y, Arai T, Okuma T, Kawata Y (2011) Long-term follow-up high-resolution CT findings in non-specific interstitial pneumonia. Thorax 66:61–65
Marie I (2012) Morbidity and mortality in adult polymyositis and dermatomyositis. Curr Rheumatol Rep 14:275–285
Zamora AC, Hoskote SS, Abascal-Bolado B et al (2016) Clinical features and outcomes of interstitial lung disease in anti-Jo-1 positive antisynthetase syndrome. Respir Med 118:39–45
Aggarwal R, Cassidy E, Fertig N et al (2014) Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients. Ann Rheum Dis 73:227–232
Miller FW, Love LA, Barbieri SA, Balow JE, Plotz PH (1990) Lymphocyte activation markers in idiopathic myositis: changes with disease activity and differences among clinical and autoantibody subgroups. Clin Exp Immunol 81:373–379
Wang DX, Lu X, Zu N et al (2012) Clinical significance of peripheral blood lymphocyte subsets in patients with polymyositis and dermatomyositis. Clin Rheumatol 31:1691–1697
Yoshida S, Akizuki M, Mimori T, Yamagata H, Inada S, Homma M (1983) The precipitating antibody to an acidic nuclear protein antigen, the Jo-1, in connective tissue diseases. A marker for a subset of polymyositis with interstitial pulmonary fibrosis. Arthritis Rheum 26:604
Stone KB, Oddis CV, Fertig N et al (2007) Anti-Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy. Arthritis Rheum 56:3125–3131
La Corte R, Lo Mo Naco A, Locaputo A, Dolzani F, Trotta F (2006) In patients with antisynthetase syndrome the occurrence of anti-Ro/SSA antibodies causes a more severe interstitial lung disease. Autoimmunity 39:249–253
Debray M, Borie R, Revel M et al (2015) Interstitial lung disease in anti-synthetase syndrome: initial and follow-up CT findings. Eur J Radiol 84:516–523
Hozumi H, Enomoto N, Kono M et al (2015) Prognostic significance of anti-aminoacyl-tRNA synthetase antibodies in polymyositis/dermatomyositis-associated interstitial lung disease: a retrospective case control study. PLoS One 10:e120313
Mirrakhimov AE (2015) Antisynthetase syndrome: a review of etiopathogenesis, diagnosis and management. Curr Med Chem 22:1963–1975
Andersson H, Aaløkken TM, Günther A et al (2016) Pulmonary involvement in the antisynthetase syndrome: a comparative cross-sectional study. J Rheumatol 43:1107–1113
Dugar M, Cox S, Limaye V, Blumbergs P, Roberts-Thomson PJ (2011) Clinical heterogeneity and prognostic features of South Australian patients with anti-synthetase autoantibodies. Intern Med J 41:674–679
Tillie-Leblond I, Wislez M, Valeyre D et al (2008) Interstitial lung disease and anti-Jo-1 antibodies: difference between acute and gradual onset. Thorax 63:53–59
Richards TJ, Eggebeen A, Gibson K et al (2009) Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum 60:2183–2192
Acknowledgments
We thank Angela Morben, DVM, ELS, from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.
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The scientific guarantor of this publication is Sheng **e.
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Informed consent was waived because this was a retrospective study.
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Liu, H., **e, S., Liang, T. et al. Prognostic factors of interstitial lung disease progression at sequential HRCT in anti-synthetase syndrome. Eur Radiol 29, 5349–5357 (2019). https://doi.org/10.1007/s00330-019-06152-5
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DOI: https://doi.org/10.1007/s00330-019-06152-5