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. 2025 Feb 12:16:1529582.
doi: 10.3389/fimmu.2025.1529582. eCollection 2025.

Ultrasensitive interferons quantification reveals different cytokine profile secretion in inflammatory myopathies and can serve as biomarkers of activity in dermatomyositis

Loïs Bolko  1   2   3 , Céline Anquetil  2   3 , Alba Llibre  4 , Solène Maillard  3 , Damien Amelin  3 , Karim Dorgham  5 , Vincent Bondet  4 , Océane Landon-Cardinal  2   6   7 , Ségolène Toquet  2   3 , Kuberaka Mariampillai  2 , Samuel Malatre  3 , Alexandrine Mahoudeau  3 , Baptiste Hervier  2 , Mathieu Rodero  8 , Guy Gorochov  5 , Darragh Duffy  4 , Olivier Benveniste  2   3 , Yves Allenbach  2   3
Affiliations

Ultrasensitive interferons quantification reveals different cytokine profile secretion in inflammatory myopathies and can serve as biomarkers of activity in dermatomyositis

Loïs Bolko et al. Front Immunol. .

Abstract

Objective: The objective of this study was to evaluate the presence of different types of interferon in idiopathic inflammatory myopathies (IIM) and their subgroups using ultrasensitive cytokine detection techniques (SIMOA) and to assess their potential as activity biomarkers.

Methods: Disease activity was measured at the time of serum collection and assessed by manual muscle testing eight (MMT8 score 0-150), muscle enzymes to calculate the Physician Global Assessment (PGA) (0-10). Patients were classified as active if PGA>5.Serum IFN-α and IFN-γ levels was measured using the single molecule array (SIMOA) technique. Serum IFN-β level was measured by Elisa. Correlation between IFN levels and disease activity were performed.

Results: We included 242 IIM patients and found a good correlation between type I Interferon (IFN) and dermatomyositis disease activity. IFN-α and IFN-β was highly correlated with disease activity (r=0.76 and r=0,58). To evaluate whether the different types of Interferons could serve as biomarkers of activity, we generated ROC curves. Patients with active DM had a higher median IFN-α level (0.49 pg/ml [0.1-3.7]) compared with non-active patients (0.03 pg/ml [0.01-0.07] p<0.05). The area under the curve was 0.90 IC95 (0.76-0.97) p<0.05. Furthermore, Myositis-specific antibodies appear to be associated with a different secretion profile; patients with anti-MDA 5 antibodies had higher level of IFN-α than most other antibodies (6.58 vs 0.14 p<0.005). NXP2 had higher IFN-β level than patients with Tif1γ antibodies.

Conclusion: Serum IFN-α level measured by SIMOA is a reliable biomarker of DM activity. Myositis-specific antibodies appear to be associated with a different secretion profile. This data needs to be confirmed in order to select the good therapeutics strategies in DM.

Keywords: Anti-synthetase syndrom; biomarker; dermatomyositis; immune mediated necrotizing myopathie; inclusion body myositis; interferon.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Interferon alpha. (B) Interferon Beta. (C) Interferon gamma. IFN levels in IIM. DM, Dermatomyositis; ASyS, Anti-synthetase syndrome; IMNM, Immune-mediated necrotizing myopathies; IBM, Inclusion body myositis; HD, healthy donors - - mean ± 3 standard deviation or positivity threshold, *: p<0.05, ** p<0.005, ***: p<0.0005, **** p<0.00005.
Figure 2
Figure 2
Correlation between IFNs and disease activity. (A) Correlation between IFN-α and DM disease activity. (B) Correlation between IFN-β and DM disease activity. (C) Correlation between IFN-α and ASyS disease activity. (D) Correlation between IFN-γ and IMNM disease activity. DM, Dermatomyositis; ASyS, Anti-synthetase syndrom; PGA, physician global assessment.
Figure 3
Figure 3
Different cytokine profile according to subgroup of myositis and antibody in DM. Each rows represent a patient, each colomn an IFN subtype and the color define the quantity of IFN secretion in pg/ml.
See this image and copyright information in PMC

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