Top

Respiratory Research

Published in:

Open Access 01-12-2019 | Pneumonia | Research

Presentations and outcomes of interstitial lung disease and the anti-Ro52 autoantibody

Authors: A. Sclafani, K. M. D’Silva, B. P. Little, E. M. Miloslavsky, J. J. Locascio, A. Sharma, S. B. Montesi

Published in: Respiratory Research | Issue 1/2019

Abstract

Background

Distinct clinical presentations of interstitial lung disease (ILD) with the myositis-specific antibodies, including anti-synthetase antibodies, are well-recognized. However, the association between ILD and the myositis-associated antibodies, including anti-Ro52, is less established. Our objectives were to compare presenting phenotypes of patients with anti-Ro52 alone versus in combination with myositis-specific autoantibodies and to identify predictors of disease progression or death.

Methods

We performed a retrospective cohort study of 73 adults with ILD and a positive anti-Ro52 antibody. We report clinical features, treatment, and outcomes.

Results

The majority of patients with ILD and anti-Ro52 had no established connective tissue disease (78%), and one-third had no rheumatologic symptoms. Thirteen patients (17.8%) required ICU admission for respiratory failure, with 84.6% all-cause mortality. Of the 73 subjects, 85.7% had a negative SS-A, and 49.3% met criteria for idiopathic pneumonia with autoimmune features (IPAF). The 50 patients with anti-Ro52 alone were indistinguishable from patients with anti-Ro52 plus a myositis-specific autoantibody. ICU admission was associated with poor outcomes (HR 12.97, 95% CI 5.07–34.0, p < 0.0001), whereas rheumatologic symptoms or ANA > = 1:320 were associated with better outcomes (HR 0.4, 95% CI 0.16–0.97, p = 0.04, and HR 0.29, 95% CI 0.09–0.81, p = 0.03, respectively).

Conclusions

Presentations of ILD with the anti-Ro52 antibody are heterogeneous, and outcomes are similar when compared to anti-Ro52 plus myositis-specific antibodies. Testing for anti-Ro52 may help to phenotype unclassifiable ILD patients, particularly as part of the serologic criteria for IPAF. Further research is needed to investigate treatment of ILD in the setting of anti-Ro52 positivity.

MyoMarker Panel 3 (RDL Reference Laboratory) includes the following tests: Anti-Jo-1 Ab, Anti-Mi-2 Ab, Anti-PL-12 Ab, Anti-PL-7 Ab, Anti-EJ Ab, Anti-OJ Ab, Anti-SRP Ab, Anti-Ku Ab, Anti-U2 RNP, Anti-PM/Scl-100 Ab, Anti-MDA5 Ab, Anti-NXP2 Ab, Anti-TIF-1γ Ab, Anti-SSA 52 kD IgG Ab, Anti-U1 RNP Ab, Anti-Fibrillarin U3 RNP Ab. http://www.rdlinc.com/test_menu/myomarker-panel-3/

Saketkoo LA, Ascherman DP, Cottin V, Christopher-Stine L, Danoff SK, Oddis CV. Interstitial lung disease in idiopathic inflammatory myopathy. Curr Rheumatol Rev. 2010;6(2):108–19.CrossRefPubMedPubMedCentral

Chen I-J, Jan Wu Y-J, Lin C-W, et al. Interstitial lung disease in polymyositis and dermatomyositis. Clin Rheumatol. 2009;28(6):639–46. https://doi.org/10.1007/s10067-009-1110-6.CrossRefPubMed

Hallowell RW, Danoff SK. Interstitial lung disease associated with the idiopathic inflammatory myopathies and the antisynthetase syndrome. Curr Opin Rheumatol. 2014;26(6):684–9. https://doi.org/10.1097/BOR.0000000000000104.CrossRefPubMed

Hallowell R, Ascherman D, Danoff S. Pulmonary manifestations of Polymyositis/Dermatomyositis. Semin Respir Crit Care Med. 2014;35(02):239–48. https://doi.org/10.1055/s-0034-1371528.CrossRefPubMed

Won Huh J, Soon Kim D, Keun Lee C, et al. Two distinct clinical types of interstitial lung disease associated with polymyositis-dermatomyositis. Respir Med. 2007;101(8):1761–9. https://doi.org/10.1016/j.rmed.2007.02.017.CrossRefPubMed

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. https://doi.org/10.1371/journal.pone.0060442.CrossRefPubMedPubMedCentral

Shi J, Li S, Yang H, et al. Clinical profiles and prognosis of patients with distinct Antisynthetase autoantibodies. J Rheumatol. 2017;44(7):1051–7. https://doi.org/10.3899/jrheum.161480.CrossRefPubMed

Solomon J, Swigris JJ, Brown KK. Myositis-related interstitial lung disease and antisynthetase syndrome. J Bras Pneumol. 2011;37(1):100–9.CrossRefPubMed

Satoh M, Tanaka S, Ceribelli A, Calise SJ, Chan EKL. A comprehensive overview on myositis-specific antibodies: new and old biomarkers in idiopathic inflammatory myopathy. Clin Rev Allergy Immunol. 2017;52(1):1–19. https://doi.org/10.1007/s12016-015-8510-y.CrossRefPubMedPubMedCentral

10.

Cassius C, Le Buanec H, Bouaziz J-D, Amode R. Biomarkers in Adult Dermatomyositis: Tools to Help the Diagnosis and Predict the Clinical Outcome. J Immunol Res. 2019;2019(9, article s139):9141420–15. https://doi.org/10.1155/2019/9141420.CrossRefPubMedPubMedCentral

11.

Vuillard C, de Chambrun MP, de Prost N, et al. Clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French multicenter retrospective study. Ann Intensive Care. 2018;8(1):755. https://doi.org/10.1186/s13613-018-0433-3.CrossRef

12.

Casciola-Rosen L, Mammen AL. Myositis autoantibodies. Curr Opin Rheumatol. 2012;24(6):602–8. https://doi.org/10.1097/BOR.0b013e328358bd85.CrossRefPubMed

13.

Dugar M, Cox S, Limaye V, Gordon TP, Roberts-Thomson PJ. Diagnostic utility of anti-Ro52 detection in systemic autoimmunity. Postgrad Med J. 2010;86(1012):79–82. https://doi.org/10.1136/pgmj.2009.089656.CrossRefPubMed

14.

Frank MB, McCubbin V, Trieu E, Wu Y, Isenberg DA, Targoff IN. The association of anti-Ro52 autoantibodies with myositis and scleroderma autoantibodies. J Autoimmun. 1999;12(2):137–42. https://doi.org/10.1006/jaut.1998.0265.CrossRefPubMed

15.

Koenig M, Fritzler MJ, Targoff IN, Troyanov Y, Senécal J-L. Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: insights into clinical features and outcomes. Arthritis Res Ther. 2007;9(4):R78. https://doi.org/10.1186/ar2276.CrossRefPubMedPubMedCentral

16.

Rutjes SA, Vree Egberts WT, Jongen P, Van Den Hoogen F, Pruijn GJ, Van Venrooij WJ. Anti-Ro52 antibodies frequently co-occur with anti-Jo-1 antibodies in sera from patients with idiopathic inflammatory myopathy. Clin Exp Immunol. 1997;109(1):32–40. https://doi.org/10.1046/j.1365-2249.1997.4081308.x.CrossRefPubMedPubMedCentral

17.

Yamasaki Y, Satoh M, Mizushima M, et al. Clinical subsets associated with different anti-aminoacyl transfer RNA synthetase antibodies and their association with coexisting anti-Ro52. Mod Rheumatol. 2016;26(3):403–9. https://doi.org/10.3109/14397595.2015.1091155.CrossRefPubMed

18.

Fiorentino D, Chung L, Zwerner J, Rosen A, Casciola-Rosen L. The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): a retrospective study. J Am Acad Dermatol. 2011;65(1):25–34. https://doi.org/10.1016/j.jaad.2010.09.016.CrossRefPubMedPubMedCentral

19.

La Corte R. Mo Naco Lo a, Locaputo a, Dolzani F, Trotta F. in patients with antisynthetase syndrome the occurrence of anti-Ro/SSA antibodies causes a more severe interstitial lung disease. Autoimmunity. 2006;39(3):249–53. https://doi.org/10.1080/08916930600623791.CrossRefPubMed

20.

Váncsa A, Csípo I, Németh J, Dévényi K, Gergely L, Dankó K. Characteristics of interstitial lung disease in SS-A positive/Jo-1 positive inflammatory myopathy patients. Rheumatol Int. 2009;29(9):989–94. https://doi.org/10.1007/s00296-009-0884-9.CrossRefPubMed

21.

Ferreira JP, Almeida I, Marinho A, Cerveira C, Vasconcelos C. Anti-Ro52 antibodies and interstitial lung disease in connective tissue diseases excluding scleroderma. ISRN Rheumatol. 2012;2012(5):1–4. https://doi.org/10.5402/2012/415272.CrossRef

22.

Schulte-Pelkum J, Fritzler M, Mahler M. Latest update on the Ro/SS-A autoantibody system. Autoimmun Rev. 2009;8(7):632–7. https://doi.org/10.1016/j.autrev.2009.02.010.CrossRefPubMed

23.

Robbins A, Hentzien M, Toquet S, et al. Diagnostic utility of separate anti-Ro60 and anti-Ro52/TRIM21 antibody detection in autoimmune diseases. Front Immunol. 2019;10:444. https://doi.org/10.3389/fimmu.2019.00444.CrossRefPubMedPubMedCentral

24.

Ghillani P, André C, Toly C, et al. Clinical significance of anti-Ro52 (TRIM21) antibodies non-associated with anti-SSA 60kDa antibodies: results of a multicentric study. - PubMed - NCBI. Autoimmun Rev. 2011;10(9):509–13. https://doi.org/10.1016/j.autrev.2011.03.004.CrossRefPubMed

25.

Travis WD, Costabel U, Hansell DM, 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):733–48. https://doi.org/10.1164/rccm.201308-1483ST.CrossRefPubMedPubMedCentral

26.

van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum. 2013;65(11):2737–47. https://doi.org/10.1002/art.38098.CrossRefPubMedPubMedCentral

27.

Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European league against rheumatism classification criteria for primary Sjögren's syndrome. Ann Rheum Dis. 2016;76(1):9–16. https://doi.org/10.1136/annrheumdis-2016-210571.CrossRefPubMed

28.

Petri M, Orbai A-M, Alarcón GS, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677–86. https://doi.org/10.1002/art.34473.CrossRefPubMedPubMedCentral

29.

Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–81. https://doi.org/10.1002/art.27584.CrossRefPubMed

30.

Alarcon-Segovia D, Villareal M. Classification and diagnostic criteria for mixed connective tissue disease. In: Kasukawa R, Sharp G, editors. Mixed connective tissue disease and anti-nuclear antibodies. Amsterdam: Elsevier; 1987.

31.

Lundberg IE, Tjärnlund 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. Arthritis Rheum. 2017;69(12):2271–82. https://doi.org/10.1002/art.40320.CrossRef

32.

Dasgupta B, Cimmino MA, Maradit-Kremers H, et al. 2012 provisional classification criteria for polymyalgia rheumatica: a European league against rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2012;71(4):484–92. https://doi.org/10.1136/annrheumdis-2011-200329.CrossRefPubMed

33.

Fischer A, Collard HR, Swigris JJ, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J. 2015;46(4):1–12. https://doi.org/10.1183/13993003.00150-2015.CrossRef

34.

Koreeda Y, Higashimoto I, Yamamoto M, et al. Clinical and pathological findings of interstitial lung disease patients with anti-aminoacyl-tRNA synthetase autoantibodies. Intern Med. 2010;49(5):361–9.CrossRefPubMed

35.

Infantino M, Palterer B, Biagiotti R, et al. Reflex testing of speckled cytoplasmic patterns observed in routine ANA HEp-2 indirect immunofluorescence with a multiplex anti-synthetase dot-blot assay: a multicentric pilot study. Immunol Res. 2018;66(1):74–8. https://doi.org/10.1007/s12026-017-8974-3.CrossRefPubMed

36.

Wilfong EM, Lentz RJ, Guttentag A, et al. Interstitial pneumonia with autoimmune features: an emerging challenge at the intersection of rheumatology and pulmonology. Arthritis Rheum. 2018;70(12):1901–13. https://doi.org/10.1002/art.40679.CrossRef

37.

Novikov P, Shchegoleva E, Akulkina L, Bulanov N, Vinogradova E, Moiseev S. Diagnostic pitfalls and treatment challenges in interstitial pneumonia with autoimmune features: comment on the article by Wilfong et al. Arthritis Rheum. 2018;70:1901. https://doi.org/10.1002/art.40783.CrossRef

38.

Bellani G, Laffey JG, Pham T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315(8):788–800. https://doi.org/10.1001/jama.2016.0291.CrossRefPubMed

39.

Gannon WD, Lederer DJ, Biscotti M, et al. Outcomes and mortality prediction model of critically ill adults with acute respiratory failure and interstitial lung disease. - PubMed - NCBI. Chest. 2018;153(6):1387–95. https://doi.org/10.1016/j.chest.2018.01.006.CrossRefPubMedPubMedCentral

40.

Garberg H, Jonsson R, Brokstad KA. The serological pattern of autoantibodies to the Ro52, Ro60, and La48 autoantigens in primary Sjögren's syndrome patients and healthy controls. Scand J Rheumatol. 2005;34(1):49–55.CrossRefPubMed

Title: Presentations and outcomes of interstitial lung disease and the anti-Ro52 autoantibody
Authors: A. Sclafani
K. M. D’Silva
B. P. Little
E. M. Miloslavsky
J. J. Locascio
A. Sharma
S. B. Montesi
Publication date: 01-12-2019
Publisher: BioMed Central
Keyword: Pneumonia
Published in: Respiratory Research / Issue 1/2019
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/s12931-019-1231-7

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2019

Primary pulmonary lymphoepithelioma-like carcinoma: a rare type of lung cancer with a favorable outcome in comparison to squamous carcinoma

COL6A3 polymorphisms were associated with lung cancer risk in a Chinese population

Modulation of blood inflammatory markers by benralizumab in patients with eosinophilic airway diseases

Feasibility of low dose chest CT for virtual bronchoscopy navigation in a porcine model

Diagnostic test interpretation and referral delay in patients with interstitial lung disease

Antioxidative effects of caffeine in a hyperoxia-based rat model of bronchopulmonary dysplasia

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials