Table 4.
Summary of questions for future clinical‐translational research
| • Does increased NET formation lead to thrombus formation in patients with ANCA‐associated vasculitis? |
| • What are the mechanisms by which NETs promote thrombus formation in patients with APS? |
| • Do levels of NETs increase during clinical events associated with APS, such as acute thrombotic episodes, or pregnancy complications, such as miscarriages or preeclampsia? |
| • How are the protein contents of NETs influenced by exposure to different autoantibodies and inflammatory cytokines? |
| • Do all patients with SLE have increased NETosis, or does only a subset of patients with specific autoantibodies have increased NETosis? |
| • In which subsets of patients with SLE does increased NETosis correlate with increased disease activity? |
| • What is the best method (ability of sera to induce NETs, NET degradation, NET products, such as cfDNA) to measure increased NET formation in SLE patients? |
| • How will we define normal NET formation versus increased NET formation? |
| • Which measurement of NETosis could be most easily performed in clinical labs? |
| • What is the role of LDGs in the pathogenesis of ANCA‐associated vasculitis? |
| • Could LDGs be potential biomarkers for ANCA‐associated vasculitis and SLE? |
| • Does NETosis correlate with an increased type I IFN signature and increased IFN‐α levels in patients with SLE? |
| • Do NETs propagate inflammation in atherosclerotic lesions in humans? |
| • Is the NET‐mediated inflammatory process in atherosclerosis more pronounced in patients with autoimmune diseases, such as SLE, compared with the general population? |
| • What are the in vivo effects of DNase I in SLE patients? |
| • What are the in vitro and in vivo effects of PAD‐4 inhibitors in SLE patients? |
| • Does eculizumab block NET formation in vitro and in vivo in SLE patients? |
| • Does vitamin D block NET formation and improve EC dysfunction in vivo in SLE patients? |
| • Do antimalarials and other commonly used medications in SLE, such as azathioprine, mycophenolate mofetil, and cyclophosphamide, block NET formation in vivo in SLE patients? |
| • Are there other subsets of type I IFN, in addition to IFN‐α, that are important drivers of SLE disease activity? |