Table 2

Key points to be considered in future research efforts

Issue considered	Comments from advisors
What drives production of type I IFNs (eg, pDCs, keratinocytes)?	What is the contribution of different cell types to IFN production, especially in tissue? Are we measuring production of IFN or downstream effects? Does the source of IFN change during the course of the disease?
What are the endogenous triggers of the immune system?	Better understanding of the pathways
Can we clearly define the signal for IFN?	What is the sensitivity of the assays? Clear signature for IFN-β versus IFN-α
What is the significance of IFN-regulated genes?	Measure IFN in various tissues What is the role of different types of IFN (I, II, III)? What is the role of IFN-α on long-lived plasma cells?
Do we have a biochemical understanding of differential signalling by the various isoforms of IFN-α as well as IFN-β?	Is there a tissue-specific difference?
What is the correlation between IFN status and phenotype?	What are the genetic susceptibility factors?
What is our understanding of the stability of IFN signature for patients with different disease activity?	N/A
What is the role of IFNGS in diseases other than lupus and classical systemic inflammatory rheumatic diseases (eg, Sjögren’s syndrome, SSc, RA), such as opportunity in HIV, psoriasis, others?	N/A
What are the effects of blocking IFN on other compensatory mechanisms?	N/A
What is our understanding of the genome-wide RNA sequencing for patients with several IFN diseases, pre-anifrolumab and post-anifrolumab?	N/A
Is there a point where a disease becomes irreversible and IFN blockage will no longer work?	N/A
How is IFN linked to sex differences in SLE?	N/A
Do we have a good understanding of the clinical and biological characteristics of IFN-low patients?	N/A

HIV, human immunodeficiency virus; IFN, interferon; IFNGS, interferon gene signature; N/A, not applicable; pDC, plasmacytoid dendritic cells; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SSc, systemic sclerosis.