Screening for Myositis Antibodies in Idiopathic Interstitial Lung Disease

Abstract

Purpose

International guidelines recommend screening for connective tissue disease (CTD) with autoantibodies when evaluating patients with idiopathic interstitial lung disease (ILD). Idiopathic inflammatory myositis comprises of a subgroup of CTD diagnosed with myositis antibodies (MA), often presenting with ILD. Our aim was to evaluate the utility of MA screening in patients with idiopathic ILD.

Methods

A retrospective analysis was conducted on patients referred with idiopathic ILD to a tertiary centre ILD clinic who were screened for MA. Patients with known or suspected CTD were excluded. Descriptive statistics, univariate analysis and multivariable logistic regression were used to detect associations between MA and patient characteristics.

Results

Of 360 patients, 165 met inclusion criteria and 44 (26.7%) were identified to have MA. Fourteen patients (8.5%) had a change in diagnosis as a result of MA screening. Multivariable logistic regression identified the presence of MA to be associated with current smoking [OR 6.87 (1.65–28.64), p = 0.008] and a diffusing capacity of < 70% predicted [OR 2.55 (1.09–5.97), p = 0.03]. In patients with a change in diagnosis due to MA screening, 3 (1.8%) underwent a surgical lung biopsy and 2 (1.2%) were previously treated with antifibrotic therapy.

Conclusions

Screening for MA in patients with idiopathic ILD can contribute to a change in patient diagnosis, and may prevent invasive testing and unproven use of antifibrotic therapy. These results support the addition of MA to CTD screening panels during the initial evaluation of idiopathic ILD.

This is a preview of subscription content, log in to check access.

Abbreviations

ANA:

Antinuclear antibodies

ARS:

Aminoacyl-tRNA synthetase antibodies

aSS:

Antisynthetase syndrome

antiCCP:

Anti-cyclic citrullinated peptide

CT:

Computed tomography

CTD:

Connective tissue disease

DLCO:

Diffusing capacity of the lung for carbon monoxide

FVC:

Forced vital capacity

GER:

Gastroesophageal reflux

IIM:

Idiopathic inflammatory myositis

ILD:

Interstitial lung disease

IPF:

Idiopathic pulmonary fibrosis

MAA:

Myositis-associated antibodies

MA:

Myositis antibodies

MSA:

Myositis-specific antibodies

NSIP:

Non-specific interstitial pneumonia

PFT:

Pulmonary function testing

RF:

Rheumatoid factor

SLB:

Surgical lung biopsy

SRP:

Anti-signal recognition particle

UIP:

Usual interstitial pneumonia

References

  1. 1.

    Mittoo S, Gelber AC, Christopher-Stine L, Horton MR, Lechtzin N, Danoff SK (2009) Ascertainment of collagen vascular disease in patients presenting with interstitial lung disease. Respir Med 103:1152–1158

    Article  PubMed  Google Scholar 

  2. 2.

    Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK 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

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ et al (2018) Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 198:e44–e68

    Article  PubMed  Google Scholar 

  4. 4.

    Idiopathic Pulmonary Fibrosis Clinical Research N, Raghu G, Anstrom KJ, King TE Jr, Lasky JA, Martinez FJ (2012) Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med 366: 1968–1977

    Article  Google Scholar 

  5. 5.

    Watanabe K, Handa T, Tanizawa K, Hosono Y, Taguchi Y, Noma S et al (2011) Detection of antisynthetase syndrome in patients with idiopathic interstitial pneumonias. Respir Med 105:1238–1247

    Article  PubMed  Google Scholar 

  6. 6.

    Ghirardello A, Borella E, Beggio M, Franceschini F, Fredi M, Doria A (2014) Myositis autoantibodies and clinical phenotypyes. Auto Immun Highlights 5:69–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Vrancken A, De Langhe E, Westhovens R, Yserbyt J, Cottin V, Wuyts W (2015) Difficulties in diagnosis of systemic sclerosis-related interstitial lung disease. Respirol Case Rep 2015 3:99–101

    PubMed  Google Scholar 

  8. 8.

    Hallowell RW, Ascherman DP, Danoff SK (2014) Pulmonary manifestations of polymyositis/dermatomyositis. Semin Respir Crit Care Med 35:239–248

    Article  PubMed  Google Scholar 

  9. 9.

    Stone KB, Oddis CV, Fertig N, Katsumata Y, Lucas M, Vogt M et al (2007) Anti-Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy. Arthritis Rheum 56:3125–3131

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Hunninghake GW, Lynch DA, Galvin JR, Gross BH, Muller N, Schwartz DA et al (2003) Radiologic findings are strongly associated with a pathologic diagnosis of usual interstitial pneumonia. Chest 124:1215–1223

    Article  PubMed  Google Scholar 

  11. 11.

    Hwang JH, Misumi S, Sahin H, Brown KK, Newell JD, Lynch DA (2009) Computed tomographic features of idiopathic fibrosing interstitial pneumonia: comparison with pulmonary fibrosis related to collagen vascular disease. J Comput Assist Tomogr 33:410–415

    Article  PubMed  Google Scholar 

  12. 12.

    Akira M (2017) Radiographic differentiation of advanced fibrocystic lung diseases. Ann Am Thorac Soc 14:432–440

    Article  PubMed  Google Scholar 

  13. 13.

    Aggarwal R, Dhillon N, Fertig N, Koontz D, Qi Z, Oddis CV (2017) A negative antinuclear antibody does not indicate autoantibody negativity in myositis: role of anticytoplasmic antibody as a screening test for antisynthetase syndrome. J Rheumatol 44:223–229

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Antoniou KM, Margaritopoulos GA, Goh NS, Karagiannis K, Desai SR, Nicholson AG et al (2016) Combined pulmonary fibrosis and emphysema in scleroderma-related lung disease has a major confounding effect on lung physiology and screening for pulmonary hypertension. Arthritis Rheumatol 68:1004–1012

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    van Wesemael TJ, Ajeganova S, Humphreys J, Terao C, Muhammad A, Symmons DP et al (2016) Smoking is associated with the concurrent presence of multiple autoantibodies in rheumatoid arthritis rather than with anti-citrullinated protein antibodies per se: a multicenter cohort study. Arthritis Res Ther 18:285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Klareskog L, Stolt P, Lundberg K, Kallberg H, Bengtsson C, Grunewald J et al (2006) A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 54:38–46

    Article  CAS  Google Scholar 

  17. 17.

    Chinoy H, Adimulam S, Marriage F, New P, Vincze M, Zilahi E et al (2012) Interaction of HLA-DRB1*03 and smoking for the development of anti-Jo-1 antibodies in adult idiopathic inflammatory myopathies: a European-wide case study. Ann Rheum Dis 71:961–965

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Lilleker JB, Vencovsky J, Wang G, Wedderburn LR, Diederichsen LP, Schmidt J et al (2018) The EuroMyositis registry: an international collaborative tool to facilitate myositis research. Ann Rheum Dis 77:30–39

    Article  PubMed  Google Scholar 

  19. 19.

    Hutchinson JP, Fogarty AW, McKeever TM, Hubbard RB (2016) In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States. 2000 to 2011. Am J Respir Crit Care Med 193:1161–1167

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    De Sadeleer LJ, De Langhe E, Bodart N, Vigneron A, Bossuyt X, Wuyts WA (2018) Prevalence of myositis-specific antibodies in idiopathic interstitial pneumonias. Lung 196:329–333

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Funding for this project was obtained from the Canadian Pulmonary Fibrosis Foundation.

Author information

Affiliations

Authors

Contributions

LF is the guarantor of this research, and takes responsibility for the integrity of this work. All authors contributed to manuscript revisions, and provided final approval of the version for publication. LF, SS and SM contributed to the study concept and design, statistical analysis, drafting of initial manuscript and study supervision. Other contributions: none.

Corresponding author

Correspondence to Lee Fidler.

Ethics declarations

Conflict of interest

SS has participated in speaking engagements and advisory boards for Hoffman-LaRoche Canada, Boehringer-Ingelheim Canada and AstraZeneca Canada. He has participated in clinical trials research for Hoffman-LeRoche Canada, Boehringer-Ingelheim Canada, Prometic Pharmaceuticals, Gilead Pharmaceuticals and Sanofi-Aventis Canada. All others have no conflicts of interest to declare.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

For this type of study, formal consent is not required.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Fidler, L., Doubelt, I., Kandel, S. et al. Screening for Myositis Antibodies in Idiopathic Interstitial Lung Disease. Lung 197, 277–284 (2019). https://doi.org/10.1007/s00408-019-00212-9

Download citation

Keywords

  • Connective tissue disease
  • Idiopathic inflammatory myositis
  • Interstitial lung disease