Abstract
This study aimed to assess the clinical utility of serum interferon-lambda 3 (IFN-λ3) as a sequential biomarker for treatment response and disease control in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM)-associated interstitial lung disease (ILD). Serum IFN-λ3 levels were measured in 24 patients with anti-MDA5 antibody-positive DM-ILD at diagnosis and 1 month after initiating immunosuppressive therapy. Patients were categorized into two groups based on clinical outcomes: a good control group (n = 16; survived without relapse for ≥ 1 year) and a poor control group (n = 8; died from ILD progression or relapse within 1 year). Changes in serum IFN-λ3 levels and differences between groups were analyzed. In the good control group, serum IFN-λ3 levels significantly decreased from 94.6 to 12.7 pg/mL (p < 0.001), whereas no significant change was observed in the poor control group (129.0 to 118.8 pg/mL). Furthermore, serum IFN-λ3 levels at 1 month were significantly lower in the good control group than in the poor control group (p = 0.004). Serum IFN-λ3 levels may reflect short-term treatment response and could serve as a useful sequential biomarker for assessing disease control in patients with anti-MDA5 antibody-positive DM-ILD.
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The data that support the findings of this study are available from the corresponding authors upon reasonable request.
References
Hozumi, H. et al. Comprehensive assessment of myositis-specific autoantibodies in polymyositis/dermatomyositis-associated interstitial lung disease. Respir. Med. 121, 91–99 (2016).
Sato, S. et al. Initial predictors of poor survival in myositis-associated interstitial lung disease: A multicentre cohort of 497 patients. Rheumatology (Oxford) 57(7), 1212–1221 (2018).
Fujisawa, T. Management of myositis-associated interstitial lung disease. Medicina (Kaunas). 57(4), 347 (2021).
Nakashima, R., Hosono, Y. & Mimori, T. Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease. Lupus 25(8), 925–933 (2016).
Zhu, Y. et al. Serum Krebs von den Lungen-6 concentrations reflect severity of anti-melanoma differentiation-associated protein 5 antibody positive dermatomyositis associated interstitial lung disease. Clin. Exp. Rheumatol. 40(2), 292–297 (2022).
Yang, Q. et al. Anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis exhibit three clinical phenotypes with different prognoses. Clin. Exp. Rheumatol. 40(2), 304–308 (2022).
Gono, T. et al. Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology (Oxford) 51(9), 1563–1570 (2012).
Broggi, A., Granucci, F. & Zanoni, I. Type III interferons: Balancing tissue tolerance and resistance to pathogen invasion. J. Exp. Med. 217(1), e20190295 (2020).
Ye, L., Schnepf, D. & Staeheli, P. Interferon-λ orchestrates innate and adaptive mucosal immune responses. Nat. Rev. Immunol. 19(10), 614–625 (2019).
Dellgren, C., Gad, H. H., Hamming, O. J., Melchjorsen, J. & Hartmann, R. Human interferon-lambda3 is a potent member of the type III interferon family. Genes Immun. 10(2), 125–131 (2009).
Amezcua-Guerra, L. M. et al. Type III interferons in systemic lupus erythematosus: Association between interferon λ3, disease activity, and anti-Ro/SSA antibodies. J. Clin. Rheumatol. 23(7), 368–375 (2017).
Metwally, M. et al. IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis. Sci. Rep. 9(1), 14834 (2019).
Wen, J. et al. Serum level of IFN-λ is elevated in idiopathic inflammatory myopathies. Clin. Rheumatol. 44(1), 327–340 (2025).
Fukada, A. et al. Prognostic role of interferon-λ3 in anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated interstitial lung disease. Arthritis Rheumatol. 76(5), 796–805 (2024).
Yoshida, A. et al. Dysregulated type I/III interferon system in circulation from patients with anti-MDA5-positive dermatomyositis. Sci. Rep. 15(1), 25537 (2025).
Bohan, A. & Peter, J. B. Polymyositis and dermatomyositis (first of two parts). N. Engl. J. Med. 292(7), 344–347 (1975).
Lundberg, I. E. 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. 76(12), 1955–1964 (2017).
Fujisawa, T. et al. Prognostic factors for myositis-associated interstitial lung disease. PLoS ONE 9(6), e98824 (2014).
Suda, T. et al. Interstitial lung diseases associated with amyopathic dermatomyositis. Eur. Respir. J. 28(5), 1005–1012 (2006).
Fujisawa, T. et al. Clinical significance of serum chitotriosidase level in anti-MDA5 antibody-positive dermatomyositis-associated interstitial lung disease. J. Rheumatol. 46(8), 935–942 (2019).
Sugiyama, M. et al. Serum CCL17 level becomes a predictive marker to distinguish between mild/moderate and severe/critical disease in patients with COVID-19. Gene 766, 145145 (2021).
Aoki, Y. et al. Association of serum IFN-λ3 with inflammatory and fibrosis markers in patients with chronic hepatitis C virus infection. J. Gastroenterol. 50(8), 894–902 (2015).
Gono, T., Okazaki, Y., Murakami, A. & Kuwana, M. Improved quantification of a commercial enzyme-linked immunosorbent assay kit for measuring anti-MDA5 antibody. Mod. Rheumatol. 29(1), 140–145 (2019).
American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am. J. Respir. Crit. Care Med. 161(2 Pt 1), 646–664 (2000).
Raghu, G. et al. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: An official ATS/ERS/JRS/ALAT clinical practice guideline. Am. J. Respir. Crit. Care Med. 205(9), e18–e47 (2022).
Kanda, Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 48(3), 452–458 (2013).
Tanizawa, K. et al. The prognostic value of HRCT in myositis-associated interstitial lung disease. Respir. Med. 107(5), 745–752 (2013).
Chen, J. Y. et al. Interferon-λ3/4 genetic variants and interferon-λ3 serum levels are biomarkers of lupus nephritis and disease activity in Taiwanese. Arthritis Res. Ther. 20(1), 193 (2018).
Dias Junior, A. G., Sampaio, N. G. & Rehwinkel, J. A balancing act: MDA5 in antiviral immunity and autoinflammation. Trends Microbiol. 27(1), 75–85 (2019).
Cassius, C. et al. MDA5(+) dermatomyositis is associated with stronger skin type I interferon transcriptomic signature with upregulation of IFN-κ transcript. J. Invest. Dermatol. 140(6), 1276–9.e7 (2020).
Ono, N. et al. The relationship between type 1 IFN and vasculopathy in anti-MDA5 antibody-positive dermatomyositis patients. Rheumatology (Oxford) 58(5), 786–791 (2019).
Zhang, S. H. et al. Aberrant activation of the type I interferon system may contribute to the pathogenesis of anti-melanoma differentiation-associated gene 5 dermatomyositis. Br. J. Dermatol. 180(5), 1090–1098 (2019).
Acknowledgements
We thank Enago for editing a draft of the manuscript.
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This work was supported by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (Grant Number 22K08231, received by TF).
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Y.Kitahara: Conception and design, data collection, data analysis and interpretation, manuscript writing. T.F: Conception and design, data collection, data analysis and interpretation, manuscript writing, and final approval of the manuscript; K.K, T.A, M.Ikeda, M.F, M.N, Y.Kaida, H.M, K.Yokomura, N.K, M.T, S.I, and D.H: Conception and design, data collection, and data analysis; K.Yamashita, M.Iwaizumi, M.M: Data analysis and interpretation; A.F, Y.I, H.Y, H.H, Y.Suzuki, M.Karayama, K.F, N.E, N.I: Data collection, data analysis, and supervision; T.S: Conception and design, manuscript writing, and administrative support. All authors have reviewed and approved the manuscript.
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Kitahara, Y., Fujisawa, T., Fukada, A. et al. Serum interferon-λ3 as a short-term biomarker of disease control in anti-MDA5-positive dermatomyositis-associated ILD. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37104-x
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DOI: https://doi.org/10.1038/s41598-026-37104-x
