We report a new inborn error of immunity, termed OTULIN-related pyoderma gangrenosum (ORP). ORP is caused by homozygosity for R57C, a separation-of-function mutation in OTULIN that impairs its binding and regulation of LUBAC but preserves its catalytic activity. ORP features inflammasome activation and sensitization of dermal cells to TNF-dependent death, pointing to TNF blockade as a therapeutic option. Read more about Barath’s work in his Nature Immunology paper and in the accompanying Research Briefing.
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