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Clinical features and outcomes of the patients with anti-glycyl tRNA synthetase syndrome

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Abstract

Objective

To analyze the clinical features and outcomes of the patients with anti-glycyl tRNA synthetase (anti-EJ) syndrome in a large Chinese cohort.

Methods

The medical records, imaging, and serologic data of patients with anti-EJ antibodies from the China-Japan Friendship Hospital database were retrospectively investigated. Anti-EJ antibodies were identified using immunoblot assay. Long-term follow-up was conducted.

Results

Anti-EJ antibodies were present in 46 (19.7%) of the 234 patients with antisynthetase syndrome (ASS), preceded by anti-Jo-1 and anti-PL-7 antibodies. The mean age of disease onset was 51.2 ± 15.9 years, and 69.6% of these patients were female. The most prevalent clinical feature was interstitial lung disease (ILD) (96.7%), which was also the most common initial manifestation, followed by fever (60.9%), mechanic’s hands (56.5%), muscle involvement (50%), and Raynaud phenomenon (8.7%). Ten (21.7%) patients developed rapidly progressive ILD (RP-ILD). Organizing pneumonia (OP) on high-resolution computed tomography (HRCT) scans (OR = 37.5, p = 0.006) and a higher C-reactive protein-to-albumin ratio (CAR) (OR = 28.3, p = 0.01) were independent risk factors for RP-ILD. Muscular pathological features were heterogeneous. Concomitant infection was noted in 63.0% of the patients during the disease course. Hypoalbuminemia (OR = 0.759, p = 0.002) was an independent risk factor for concomitant infection. Patients responded well to glucocorticoid therapy. The 5- and 10-year survival rates of the patients with anti-EJ were 97.8% and 88%, respectively.

Conclusion

Anti-EJ syndrome was found to be a relatively common ASS subtype, with a favorable outcome. A notable proportion of the patients experienced RP-ILD, which was prone to OP on HRCT and a higher CAR, and needed aggressive management.

Key Points

• ILD was the most common initial manifestation of anti-glycyl tRNA synthetase syndrome.

• RP-ILD was notable in anti-EJ positive patients.

• Anti-EJ positive patients possessed a favorable long-term prognosis, but easily relapsed.

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References

  1. Targoff IN (1992) Autoantibodies in polymyositis. Rheum Dis Clin N Am 18(2):455–482

    CAS  Google Scholar 

  2. 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(5):604–611

    Article  CAS  Google Scholar 

  3. Mathews MB, Reichlin M, Hughes GR, Bernstein RM (1984) Anti-threonyl-tRNA synthetase, a second myositis-related autoantibody. J Exp Med 160(2):420–434

    Article  CAS  Google Scholar 

  4. Targoff IN (1990) Autoantibodies to aminoacyl-transfer RNA synthetases for isoleucine and glycine. Two additional synthetases are antigenic in myositis. J Immunol 144(5):1737–1743

    CAS  PubMed  Google Scholar 

  5. Bunn CC, Bernstein RM, Mathews MB (1986) Autoantibodies against alanyl-tRNA synthetase and tRNAAla coexist and are associated with myositis. J Exp Med 163(5):1281–1291

    Article  CAS  Google Scholar 

  6. Hirakata M, Suwa A, Nagai S, Kron MA, Trieu EP et al (1999) Anti-KS: identification of autoantibodies to asparaginyl-transfer RNA synthetase associated with interstitial lung disease. J Immunol 162(4):2315–2320

    CAS  PubMed  Google Scholar 

  7. Betteridge Z, Gunawardena H, North J, Slinn J, McHugh N (2007) Anti-synthetase syndrome: a new autoantibody to phenylalanyl transfer RNA synthetase (anti-Zo) associated with polymyositis and interstitial pneumonia. Rheumatology (Oxford) 46(6):1005–1008

    Article  CAS  Google Scholar 

  8. Hashish L, Trieu EP, Sadanandan P, Targoff IN (2005) Identification of autoantibodies to tyrosyl-tRNA synthetase in dermatomyositis with features consistent with antisynthetase syndrome. Arthritis Rheum 52(Suppl 9):S312

    Google Scholar 

  9. Hamaguchi Y, Fujimoto M, Matsushita T, Kaji K, Komura K, Hasegawa M, Kodera M, Muroi E, Fujikawa K, Seishima M, Yamada H, Yamada R, Sato S, Takehara K, Kuwana M (2013) Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: heterogeneity within the syndrome. PLoS One 8(4):e60442. https://doi.org/10.1371/journal.pone.0060442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hervier B, Devilliers H, Stanciu R, Meyer A, Uzunhan Y, Masseau A, Dubucquoi S, Hatron PY, Musset L, Wallaert B, Nunes H, Maisonobe T, Olsson NO, Adoue D, Arlet P, Sibilia J, Guiguet M, Lauque D, Amoura Z, Hachulla E, Hamidou M, Benveniste O (2012) Hierarchical cluster and survival analyses of antisynthetase syndrome: phenotype and outcome are correlated with anti-tRNA synthetase antibody specificity. Autoimmun Rev 12(2):210–217. https://doi.org/10.1016/j.autrev.2012.06.006

    Article  CAS  PubMed  Google Scholar 

  11. Aggarwal R, Cassidy E, Fertig N, Koontz DC, Lucas M, Ascherman DP, Oddis CV (2014) Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients. Ann Rheum Dis 73(1):227–232. https://doi.org/10.1136/annrheumdis-2012-201800

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mahler M, Miller FW, Fritzler MJ (2014) Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review. Autoimmun Rev 13(4–5):367–371. https://doi.org/10.1016/j.autrev.2014.01.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Solomon J, Swigris JJ, Brown KK (2011) Myositis-related interstitial lung disease and antisynthetase syndrome. J Bras Pneumol 37(1):100–109

    Article  Google Scholar 

  15. Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA 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(6):733–748. https://doi.org/10.1164/rccm.201308-1483ST

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kazerooni EA, Martinez FJ, Flint A, Jamadar DA, Gross BH et al (1997) Thin-section CT obtained at 10-mm increments versus limited three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring. AJR Am J Roentgenol 169(4):977–983

    Article  CAS  Google Scholar 

  17. Fujiki Y, Kotani T, Isoda K, Ishida T, Shoda T et al (2018) Evaluation of clinical prognostic factors for interstitial pneumonia in anti-MDA5 antibody-positive dermatomyositis patients. Mod Rheumatol 28(1):133–140. https://doi.org/10.1080/14397595.2017.1318468

    Article  CAS  PubMed  Google Scholar 

  18. Gono T, Kawaguchi Y, Satoh T, Kuwana M, Katsumata Y, Takagi K, Masuda I, Tochimoto A, Baba S, Okamoto Y, Ota Y, Yamanaka H (2010) Clinical manifestation and prognostic factor in anti-melanoma differentiation-associated gene 5 antibody-associated interstitial lung disease as a complication of dermatomyositis. Rheumatology (Oxford) 49(9):1713–1719. https://doi.org/10.1093/rheumatology/keq149

    Article  CAS  Google Scholar 

  19. Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I et al (2016) 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Rev Esp Cardiol (Engl Ed) 69(2):177

    Article  Google Scholar 

  20. Rider LG, Giannini EH, Brunner HI, Ruperto N, James-Newton L, Reed AM, Lachenbruch PA, Miller FW, International Myositis Assessment and Clinical Studies Group (2004) International consensus on preliminary definitions of improvement in adult and juvenile myositis. Arthritis Rheum 50(7):2281–2290

    Article  Google Scholar 

  21. Yamasaki Y, Satoh M, Mizushima M, Okazaki T, Nagafuchi H, Ooka S, Shibata T, Nakano H, Ogawa H, Azuma K, Maeda A, Tonooka K, Ito H, Takakuwa Y, Inoue M, Mitomi H, Kiyokawa T, Tsuchida K, Matsushita H, Mikage H, Murakami Y, Chan JY, Ozaki S, Yamada H (2016) Clinical subsets associated with different anti-aminoacyl transfer RNA synthetase antibodies and their association with coexisting anti-Ro52. Mod Rheumatol 26(3):403–409. https://doi.org/10.3109/14397595.2015

    Article  CAS  PubMed  Google Scholar 

  22. Shi J, Li S, Yang H, Zhang Y, Peng Q, Lu X, Wang G (2017) Clinical profiles and prognosis of patients with distinct Antisynthetase autoantibodies. J Rheumatol 44(7):1051–1057. https://doi.org/10.3899/jrheum.161480

    Article  CAS  PubMed  Google Scholar 

  23. Sasano H, Hagiwara E, Kitamura H, Enomoto Y, Matsuo N, Baba T, Iso S, Okudela K, Iwasawa T, Sato S, Suzuki Y, Takemura T, Ogura T (2016) Long-term clinical course of anti-glycyl tRNA synthetase (anti-EJ) antibody-related interstitial lung disease pathologically proven by surgical lung biopsy. BMC Pulm Med 16(1):168

    Article  Google Scholar 

  24. Ishizuka M, Nagata H, Takagi K, Iwasaki Y, Shibuya N, Kubota K (2016) Clinical significance of the C-reactive protein to albumin ratio for survival after surgery for colorectal cancer. Ann Surg Oncol 23(3):900–907. https://doi.org/10.1245/s10434-015-4948-7

    Article  PubMed  Google Scholar 

  25. Ha YJ, Hur J, Go DJ, Kang EH, Park JK et al (2018) Baseline peripheral blood neutrophil-to-lymphocyte ratio could predict survival in patients with adult polymyositis and dermatomyositis: a retrospective observational study. PLoS One 13(1):e0190411. https://doi.org/10.1371/journal.pone.0190411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Svensson J, Holmqvist M, Lundberg IE, Arkema EV (2017) Infections and respiratory tract disease as risk factors for idiopathic inflammatory myopathies: a population-based case-control study. Ann Rheum Dis 76(11):1803–1808. https://doi.org/10.1136/annrheumdis-2017-211174

    Article  PubMed  Google Scholar 

  27. Yuwen P, Chen W, Lv H, Feng C, Li Y, Zhang T, Hu P, Guo J, Tian Y, Liu L, Sun J, Zhang Y (2017) Albumin and surgical site infection risk in orthopaedics: a meta-analysis. BMC Surg 17(1):7. https://doi.org/10.1186/s12893-016-0186-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Oh DH, Kim YC, Kim EJ, Jung IY, Jeong SJ, Kim SY, Park MS, Kim A, Lee JG, Paik HC (2019) Multidrug-resistant Acinetobacter baumannii infection in lung transplant recipients: risk factors and prognosis. Infect Dis (Lond) 51(7):493–501. https://doi.org/10.1080/23744235.2018.1556400

    Article  CAS  Google Scholar 

  29. Hozumi H, Fujisawa T, Nakashima R, Yasui H, Suzuki Y, Kono M, Karayama M, Furuhashi K, Enomoto N, Inui N, Nakamura Y, Mimori T, Suda T (2019) Efficacy of glucocorticoids and calcineurin inhibitors for anti-aminoacyl-tRNA synthetase antibody-positive polymyositis/dermatomyositis-associated interstitial lung disease: a propensity score-matched analysis. J Rheumatol 46(5):509–517. https://doi.org/10.3899/jrheum.180778

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Qinlin Peng, Lin Liang, Yamei Zhang, Lifang Ye, Yawen Shen, Hongxia Yang from China-Japan Friendship Hospital, Beijing, China, and Lili Jiang from Jiangxi Provincial People’s hospital, Nanchang, Jiangxi, China for their assistance and advice.

Funding

This study was supported by the National Natural Science Foundation of China (81571603), and Beijing Municipal Science and Technology Commission (Z181100001718063, Z171100001017208).

Author information

Authors and Affiliations

  1. Department of Rheumatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Yinli Zhang & Shengyun Liu

  2. Department of Rheumatology, China-Japan Friendship Hospital, Beijing, 100029, China

    Yongpeng Ge, Hanbo Yang, He Chen, Xiaolan Tian, Xin Lu & Guochun Wang

  3. Department of Radiology, China-Japan Friendship Hospital, Beijing, China

    Zhenguo Huang

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  1. Yinli Zhang
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Contributions

Yinli Zhang, Xin Lu and Guochun Wang designed the study; Yinli Zhang and Yongpeng Ge enrolled subjects and collected data; Yinli Zhang, Hanbo Yang and He Chen analyzed the data; Xiaolan Tian and Zhenguo Huang reviewed the CT scans; Yinli Zhang, Shengyun Liu and Guochun Wang discussed the results and wrote the manuscript. All authors reviewed the manuscript.

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Correspondence to Guochun Wang.

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Zhang, Y., Ge, Y., Yang, H. et al. Clinical features and outcomes of the patients with anti-glycyl tRNA synthetase syndrome. Clin Rheumatol 39, 2417–2424 (2020). https://doi.org/10.1007/s10067-020-04979-8

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  • DOI: https://doi.org/10.1007/s10067-020-04979-8

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