IMMUNOLOGY2026™ Conference Recordings For Attendees-A novel inborn error of immunity perturbs linear ubiquitin homeostasis and causes pyoderma gangrenosum

A novel inborn error of immunity perturbs linear ubiquitin homeostasis and causes pyoderma gangrenosum

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Video Summary

Researchers described a new childhood-onset, monogenic form of pyoderma gangrenosum (PG) caused by homozygous R57C mutations in <strong>oculin</strong>, a linear deubiquitinase. Unlike other oculin-related disease (ORAS), this variant leaves catalytic activity intact but disrupts binding to the LUBAC complex by increasing phosphorylation near the HOIP-binding site. Patient cells showed normal NF-κB signaling but abnormal inflammasome activation, especially in monocytes, with elevated IL-1β and IL-8. In skin cells, the mutation caused excessive linear ubiquitin accumulation and heightened TNF-dependent apoptotic cell death, which was rescued by wild-type oculin but not by R57C. A patient with recurrent steroid-refractory lesions improved markedly with anti-TNF therapy. The study establishes a genetic and mechanistic basis for a novel recessive IEI causing PG and suggests targeted treatment options.

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Date April 18, 2026 8:05 AM - 8:25 AM

Room 104C

Session Surprising Insights on Human Immunology from the Study of Monogenic Inborn Errors of Immunity, Sponsored by the Clin. Immunol. Soc. (CIS)

Speaker Janet Markle

Track Human/translational immunology

Year 2026

Keywords

pyoderma gangrenosum

oculin R57C

LUBAC complex

inflammasome activation

IL-1β

anti-TNF therapy

April 18, 2026 8:05 AM - 8:25 AM

104C

Surprising Insights on Human Immunology from the Study of Monogenic Inborn Errors of Immunity, Sponsored by the Clin. Immunol. Soc. (CIS)

Janet Markle

Human/translational immunology

2026