Protein sequences homologous to the structure-associated sequences were retrieved by reciprocal Blast searching of 85 complete gamma-proteobacterial proteomes (see supplementary material, Supplementary Material online), only considering reciprocal hits with E values < 10−4 where the length of the whole protein was within the range of ±25% of the structure sequence.
See details in Materials in the online-only Data Supplement.
To confirm these results, we compared these pathways suppressed by sifalimumab to four primary gene signatures that were elevated in muscle biopsies in a previous study evaluating 31 dermatomyositis or polymyositis patients 26 (see supplementary material, available online only).
Dermatomyositis (n=26) or polymyositis (n=25) patients enrolled in this study were screened using their baseline 13 IFNGS described previously 15 (detailed in supplementary material, available online only), then randomly assigned to either placebo or sifalimumab groups.
Exclusion criteria included treatment with immunosuppressive therapies 3 months before baseline (including prednisone equivalent >10 mg), pregnancy, serious medical conditions, diffusion capacity of carbon monoxide (DLCO) less than 30% predicted, or ejection fraction (EF) less than 50% (see supplementary material, available online only).
All AE captured regardless of attribution are presented as supplementary material, available online only.
A β-catenin targeting vector was constructed as described in the supplementary material available online only.
Mice and embryos were genotyped as described in the supplementary material, available online only.
Additional background information on PML is provided in the supplementary material, available online only.
Data that have emerged from recent RCT are summarised in the supplementary material available online only.
