New data in causes of autoinflammatory diseases

Publication date: Available online 22 November 2018Source: Joint Bone SpineAuthor(s): Isabelle Koné-Paut, Sophie Georgin Lavialle, Caroline Galeotti, Linda Rossi-Semerano, Véronique Hentgen, Léa Savey, David Saadoun, Guillaume Sarrabay, Isabelle TouitouAbstractThe spectrum of factors known to mediate autoinflammation has broadened recently to include not only interleukin-1 (IL-1) and interferon, but also abnormalities that impair NF-κB pathway negative regulation. The NF-κB pathway is activated upon contact of a ligand with tumor necrosis factor receptor 1 (TNFR1) and plays a pivotal role in triggering the inflammatory process by producing major cytokines such as IL-1, IL-6, and TNF. Negative regulation of the NF-κB pathway, which is essential to stop the inflammatory process, depends on the level of ubiquitination of the proteins associated with TNFR1 and of other intermediate compounds. A20 and otulin are proteins that influence the level of ubiquitination, and a deficiency in either can result in NF-κB activation with overproduction of proinflammatory cytokines. Similar to Behçet’s disease, A20 haploinsufficiency manifests as oral and genital ulcers and, more rarely, as uveitis. However, transmission is dominant, symptom onset occurs at a younger age, and severe gastrointestinal involvement is at the forefront of the clinical picture. Clinical presentations are extremely diverse. Over their lifetime, affected patients simultaneously or sequentially experience aut...
Source: Joint Bone Spine - Category: Orthopaedics Source Type: research