Fig. 5.

Schematic depicting associations between RA disease progression and IFN-𝛂 levels over time. There is increasing evidence that IFN-I is increased at RA disease onset and in at-risk cohorts. Proposed triggers include environmental influences including infection on the background of genetic risk; however, when these events may occur in relation to disease onset or initial immune dysfunction, with regards to autoantibody generation, is unclear. There is emerging evidence that this IFN-α exposure in early RA populations may cause potentially pathogenic epigenetic changes in key cellular subsets which could persist into established disease. IFN-𝛂, interferon-𝛂; RA, rheumatoid arthritis