POS0233 DISTINCT CYTOKINE PROFILE WITH ELEVATED TYPE I/II/III INTERFERONS IN CIRCULATION FROM PATIENTS WITH ANTI-MDA5 ANTIBODY-POSITIVE DERMATOMYOSITIS

• Published in: Annals of the rheumatic diseases Vol. 83; no. Suppl 1; p. 247
• Main Authors: Yoshida, A., Gono, T., Okazaki, Y., Kuwana, M.
• Format: Journal Article
• Language: English
• Published: Kidlington BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2024; Elsevier Limited
• Subjects: Antibodies; Antiviral drugs; Biomarkers; Coronaviruses; COVID-19; Cytokines; Cytokines and Chemokines; Dermatomyositis; Enzyme-linked immunosorbent assay; IL-1β; Interleukin 10; Interleukin 6; Interleukin 8; Lung diseases; Melanoma; Monocytes; Myositis; Patients; Pharmaceuticals; Phenotypes; Pneumonia; Rheumatology; Scientific Abstracts; Serum levels; Systemic lupus erythematosus; Tumor necrosis factor-α; α-Interferon; β-Interferon; γ-Interferon
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2024-eular.3674

Background:Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) is often complicated with rapidly progressive interstitial lung disease (RP-ILD) and associated with early mortality. Previous studies indicated the role of type I interferons (IFNs) in the pathogenesis of anti-MDA5 antibody-positive DM [1]. Recently, a striking similarity of clinical features and serum cytokine profiles between anti-MDA5 antibody-positive DM-ILD and severe coronavirus disease 2019 (COVID-19) pneumonia has been noted. In severe COVID-19, serum IFN-λ3, a type III IFN, is elevated in the early disease course and suggested as a prognostic biomarker. Interestingly, a recent multicenter study demonstrated in patients with myositis-associated ILD, IFN-λ3 was elevated exclusively in those with anti-MDA5 antibodies and associated with poor prognosis [2].Objectives:We explored a characteristic serum cytokine profile in patients with anti-MDA5 antibody-positive DM, with a particular focus on type I/II/III IFNs, in comparison with other systemic autoimmune rheumatic diseases and COVID-19 pneumonia.Methods:This study enrolled consecutive patients with anti-MDA5 antibody-positive DM (n = 10), anti-synthetase antibodies (n = 6), anti-transcription intermediary factor 1-γ (TIF1-γ) antibody-positive DM (n = 6), systemic lupus erythematosus (SLE) (n = 6), COVID-19 pneumonia (n = 3), who visited Nippon Medical School Hospital from September 2020 to August 2023, as well as healthy controls (n = 5). Pre-treatment serum IFN-α, IFN-γ, IL-1β, IL-6, IL-8, IL-10, and TNF-α were measured by cytometric bead array, while IFN-β and IFN-λ3 were measured by enzyme-linked immunosorbent assay. Results are shown as median [interquartile range]. Z score was calculated to standardize data for radar chart and heat map visualization.Results:The median age of patients with anti-MDA5 antibody-positive DM was 57 years and 80% were female. Of these, nine were classified as amyopathic DM according to the 2017 American College of Rheumatology/European League Against Rheumatism classification criteria for idiopathic inflammatory myopathies. All the 10 patients had ILD and two were complicated with RP-ILD. A radar chart shows serum levels of individual cytokines according to the disease categories (Figure 1A). IFN-α was the highest in SLE (52.2 [16.5–60.9] pg/mL), followed by anti-MDA5 antibody-positive DM (23.1 [4.1–34.8] pg/mL). Elevation of IFN-β was found in anti-MDA5 antibody-positive DM (10.2 [5.7–11.8] pg/mL), while two patients with anti-TIF1-γ antibody-positive classic DM showed remarkably increased levels (30.6, 76.6 pg/mL). IFN-γ was increased in anti-MDA5 antibody-positive DM (7.4 [1.8–10.1] pg/mL) and COVID-19 pneumonia (7.5 [7.2–8.6] pg/mL) compared to other groups. Notably, IFN-λ3 was elevated in anti-MDA5 antibody-positive DM (77.4 [42.4–103.5] pg/mL), with the median level being higher than the level in a patient with severe COVID-19 pneumonia (26.4 pg/mL). On the other hand, IL-6, IL-8, and IL-10 were elevated in COVID-19 pneumonia, but not in anti-MDA5 antibody-positive DM. There was no difference in the levels of IL-1β and TNF-α between the disease categories. A clustering heatmap in individual subjects demonstrated distinct serum cytokine profiles among the disease categories, although there was substantial heterogeneity among patients (Figure 1B). Anti-MDA antibody-positive DM was characterized by the increased levels of all three IFN types, including IFN-β, IFN-γ, and IFN-λ3, while the elevation of IL-6, IL-8, and IL-10 was the hallmark of COVID-19 pneumonia.Conclusion:Patients with anti-MDA5 antibody-positive DM exhibited a distinct serum cytokine profile with elevated type I/II/III IFNs, namely IFN-β, IFN-γ, and IFN-λ3.REFERENCES:[1] Gono T, Okazaki Y, Kuwana M. Antiviral proinflammatory phenotype of monocytes in anti-MDA5 antibody-associated interstitial lung disease. Rheumatology (Oxford) 2022;61:806–14.[2] Fukada A, Fujisawa T, Hozumi H, Koda K, Akamatsu T, Oyama Y, et al. Arthritis Rheumatol 2023. doi: 10.1002/art.42785. Epub ahead of print.Acknowledgements:NIL.Disclosure of Interests:Akira Yoshida: None declared, Takahisa Gono Asahi Kasei Pharma, Astellas, Boehringer-Ingelheim, Bristol-Myers Squibb, Chugai, Eli Lily, Ono Pharmaceuticals, and Tanabe-Mitsubishi, Yuka Okazaki: None declared, Masataka Kuwana Asahi Kasei Pharma, Boehringer-Ingelheim, Chugai, Eisai, Janssen, Kissei, Mochida, Nippon Shinyaku, and Ono Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Chugai, GSK, Kissei, and Mochida, Boehringer-Ingelheim, MBL, and Ono Pharmaceuticals.