An Update on Autoinflammatory Diseases: Relopathies.
Curr Rheumatol Rep
; 20(7): 39, 2018 05 30.
Article
en En
| MEDLINE
| ID: mdl-29846841
ABSTRACT
PURPOSE OF REVIEW The nuclear factor κB (NF-κB) pathway is tightly regulated through multiple posttranslational mechanisms including ubiquitination. Mutations in these regulatory pathways can cause disease and are the focus of this review. RECENT FINDINGS:
The linear ubiquitin chain assembly complex (LUBAC) is a trimer made up of HOIL-1L, SHARPIN, and the catalytic subunit HOIP. Loss of function mutations in HOIL-1L and HOIP result in largely overlapping phenotypes, characterized by multi-organ autoinflammation, immunodeficiency, and amylopectinosis. Interestingly, patient fibroblasts exhibited diminished IL-1ß- and TNF-induced NF-κB activation, yet monocytes were hyper-responsive to IL-1ß, hinting at cell type or target specific roles of LUBAC-mediated ubiquitination. Ubiquitin-driven signaling is counterbalanced by deubiquitinase enzymes (DUBs), such as OTULIN and A20. Hypomorphic mutations in OTULIN result in elevated NF-κB signaling causing an autoinflammatory syndrome. Similarly, patients with high-penetrance heterozygous mutations in the gene encoding A20 (haploinsufficiency of A20 (HA20)) display excessive ubiquitination and increased activity of NF-κB and of NLRP3 inflammasome activation. HA20 patients present with Behçet-like characteristics or an autoimmune lymphoproliferative syndrome (ALPS)-like phenotype, indicating diverse protein functions. This review summarizes recent discoveries in the field of NF-kB-related autoinflammatory diseases (relopathies) within the past 3 years and points to several questions that still remain unanswered.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinflamatorias Hereditarias
Límite:
Humans
Idioma:
En
Revista:
Curr Rheumatol Rep
Asunto de la revista:
REUMATOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Australia