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

Behere A, Mildner H, Peralta Garcia I, Pérez Bucio C, Lundberg I, Horuluoglu B, Landegren N

RMD Open 11 (3) - [2025-09-25; online 2025-09-25]

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

PubMed 40998521

DOI 10.1136/rmdopen-2025-005836

Crossref 10.1136/rmdopen-2025-005836

pmc: PMC12481268
pii: rmdopen-2025-005836