Using data from a Sjogren's registry, researchers have shown that IFNα drives Sjögren's disease, and can be elevated a decade before diagnosis. This study assessed the role of type 1 interferon (IFNα) in its onset and in establishing a Sjögren's disease endotype.
Data was drawn from two cohorts: the UK Primary Sjögren's Syndrome Registry (UKPSSR), and UK Biobank (a large population-based cohort which includes people with and without Sjögren's disease), to study the role of IFNα in Sjögren's disease. IFNα was assayed using an ultrasensitive single molecule ELISA. The study included 177 people with Sjögren's disease from UKPSSR (mean age 57 yrs' 92% women) and from the UK Biobank - 47 606 people without Sjögren's disease and 257 with Sjögren's disease.
IFNα concentrations were elevated in 108 (61%) of 177 people with Sjögren's disease in the UKPSSR. IFN signatures were detected up to 14 years before diagnosis of Sjögren's disease in the UK Biobank Pharma Proteomics Project.
From the UKPSSR cohort - SjD with elevated, their immunological endotype characterised by cytopenia, hypergammaglobulinaemia, multiple autoantibodies, and autoimmunity against the Sjögren autoantigen TRIM21/Ro52. Nevertheless, those SjD with and without an elevated IFNα concentration were clinically similar even though they were immunologically distinct.
Using a mouse model of systemic chronic IFNα elevation, in which IFNα4 was overexpressed by conventional dendritic cells, the key features of the endotype were recapitulated and could be partly reversed by type 1 interferon receptor (IFNAR1) blockade. Thus chronic IFNα elevation has the potential to establish persistent immune dysregulation, which responded only partly to IFNAR1 blockade.
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