1. Academic Validation
  2. Idiopathic inflammatory myopathies lack neutralising autoantibodies to type- I, II and III interferons

Idiopathic inflammatory myopathies lack neutralising autoantibodies to type- I, II and III interferons

  • RMD Open. 2025 Sep 25;11(3):e005836. doi: 10.1136/rmdopen-2025-005836.
Anish Behere 1 Hedvig Mildner 2 Irene Peralta Garcia 3 4 5 César Pérez Bucio 2 Ingrid Lundberg 3 4 5 Begum Horuluoglu # 4 5 Nils Landegren # 2 5
Affiliations

Affiliations

  • 1 Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden anish.behere@imbim.uu.se.
  • 2 Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
  • 3 Department of Gastro, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
  • 4 Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
  • 5 Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • # Contributed equally.
Abstract

Objective: To determine whether autoantibodies against interferons are present and play a role in disease modulation in idiopathic inflammatory myopathies (IIMs).

Methods: We screened for autoantibodies against a large number of interferons (IFNs) and Other cytokines in a cross-sectional observational cohort of Swedish patients with anti-synthetase syndrome (n=51) and dermatomyositis (n=48), matched together with blood donors (n=100) from general population, using both planar and suspension-based multiplex assays. A single patient with autoimmune polyendocrine syndrome, type-1 (APS-1), known to harbour autoantibodies that neutralise type-I interferons, was included as a reference biological positive. The functional ability of autoantibodies to neutralise type-I interferons was tested in vitro, using an IFN-α/β responsive cell reporter assay.

Result: The initial screening of plasma samples indicated a repertoire of autoantibodies in IIM patients against a number of common myositis-specific and myositis-associated antigens. On screening for autoantibodies against type-I, II or III interferons, we did not find any evidence of anti-IFN autoantibodies being present in any of the IIM patient subgroups or the blood donors from general population. Additionally, none of the tested plasma samples, except the APS-1, exhibited neutralisation of physiological concentration IFN-α2, further confirming a complete lack of functional autoantibodies against IFN-α subtypes in this cohort.

Conclusions: We did not detect neutralising autoantibodies against IFN-α and autoantibodies against Other types of IFNs in a Swedish cohort of IIM patients. These findings contrast with the presence of autoantibodies against type-I IFNs in Other systemic autoimmune diseases, such as systemic lupus erythematosus, characterised by type-I IFN overactivation.

Keywords

Autoantibodies; Autoimmune Diseases; Autoimmunity; Cytokines; Dermatomyositis.

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