An Update on Autoinflammatory Diseases: Relopathies.

Current Rheumatology Reports
Annemarie SteinerSophia Davidson

Abstract

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. 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-1β- and TNF-induced NF-κB activation, yet monocytes were hyper-responsive to IL-1β, 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 autoi...Continue Reading

References

Sep 29, 2006·The EMBO Journal·Takayoshi KirisakoKazuhiro Iwai
Feb 29, 2008·Cytokine·Yong-Chen LuPamela S Ohashi
Jun 7, 2008·Cellular and Molecular Life Sciences : CMLS·L VerstrepenR Beyaert
Jan 13, 2009·Nature Cell Biology·Fuminori TokunagaKazuhiro Iwai
Mar 24, 2009·Annual Review of Immunology·Sivakumar Vallabhapurapu, Michael Karin
Feb 4, 2012·Genes & Development·Matthew S Hayden, Sankar Ghosh
Jun 27, 2013·Annals of Neurology·Johanna NilssonAnders Oldfors
Aug 15, 2013·The EMBO Journal·Yoshiteru SasakiKazuhiro Iwai
Aug 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Christoph H EmmerichPhilip Cohen
Sep 14, 2013·The Journal of Biological Chemistry·Judith J SmitTitia K Sixma
Jan 28, 2014·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Tsuyoshi TakiuchiKazuhiro Iwai
Apr 15, 2014·Molecular Cell·Paul R ElliottDavid Komander
Apr 15, 2014·Molecular Cell·Veronique SchaefferIvan Dikic
Jun 25, 2014·The Journal of Experimental Medicine·Mary A RodgersJae U Jung
Jul 22, 2014·Nature·Lieselotte Vande WalleMohamed Lamkanfi
Jul 26, 2014·The FEBS Journal·Berthe K Fiil, Mads Gyrd-Hansen
May 27, 2015·The Journal of Experimental Medicine·Bertrand BoissonLuigi D Notarangelo
Jun 19, 2015·Immunological Reviews·Katsuhiro Sasaki, Kazuhiro Iwai
Aug 26, 2016·Proceedings of the National Academy of Sciences of the United States of America·Qing ZhouIvona Aksentijevich
Nov 16, 2016·The Journal of Allergy and Clinical Immunology·Masatoshi TakagiTomohiro Morio
Apr 28, 2017·Open Biology·Katrin Rittinger, Fumiyo Ikeda
May 6, 2017·Cell Death and Differentiation·Philip Cohen, Sam Strickson
Jul 1, 2017·Annals of the Rheumatic Diseases·Christopher J A DuncanSophie Hambleton

❮ Previous
Next ❯

Citations

Oct 16, 2018·Current Opinion in Pediatrics·M Cecilia Poli
Mar 7, 2019·International Immunology·Heledd H Jarosz-GriffithsMichael F McDermott
May 13, 2020·Zeitschrift für Rheumatologie·T KallinichH Wittkowski
Dec 19, 2018·Frontiers in Pediatrics·Selcan DemirSeza Ozen
Feb 16, 2019·Frontiers in Immunology·David B Beck, Ivona Aksentijevich
Nov 27, 2019·Rheumatology·Mark KacarSinisa Savic
Sep 6, 2020·Scandinavian Journal of Immunology·Sandro F PerazzioMikko R J Seppänen
Nov 27, 2020·International Journal of Molecular Sciences·Rossella GrattonSergio Crovella
Nov 17, 2020·Frontiers in Immunology·Sandro F PerazzioAlexandre W S de Souza
Feb 20, 2021·The Journal of Experimental Medicine·Ommar OmarjeeAlexandre Belot
Aug 4, 2020·Journal of Translational Autoimmunity·Achille MarinoRolando Cimaz
Jan 29, 2019·La Presse médicale·Sophie Georgin-LavialleGilles Grateau
Jun 18, 2020·Best Practice & Research. Clinical Rheumatology·Sophie Georgin-LavialleVéronique Hentgen
May 1, 2021·Journal of Clinical Medicine·Carl Christoph GoetzkeTilmann Kallinich
Jun 24, 2021·Journal of Clinical Immunology·Yvan JamillouxIsabelle Meunier
Jul 3, 2021·International Journal of Molecular Sciences·Giulia Di DonatoFrancesco Chiarelli

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Lymphoproliferative Syndrome

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of abnormal lymphocyte survival caused by defective Fas mediated apoptosis. Discover the latest research on ALPS here.