OTULIN-Related Autoinflammatory Syndrome With a Novel Mutation Treated With Tumor Necrosis Factor Inhibitor Therapy: A Rare Case Report

Ubiquitylation, a posttranslational modification, is one of the key mechanisms regulating cellular homeostasis in the innate immune system. OTULIN is a deubiquitinase that prevents the accumulation of linear ubiquitin chains in the cell. OTULIN deficiency causes OTULIN-related autoinflammatory syndrome (ORAS), also known as otulipenia, an autosomal recessive disease characterized by uncontrolled inflammation. Defects in OTULIN activity result in hyperubiquitylation and inflammation due to increased activity of the nuclear factor-κB (NF-κB) pathway. At the molecular level, OTULIN-deficient humans and mice have been shown to exhibit increased levels of linear ubiquitin chains following increased tumor necrosis factor (TNF) receptor 1 (TNFR1) signaling and TNF stimulation compared to control cells. Therefore, OTULIN is considered crucial for preventing TNF-associated systemic inflammation.1