Volltext-Downloads (blau) und Frontdoor-Views (grau)

Case report: Novel variants in RELA associated with familial Behcet's-like disease

  • RELA haploinsufficiency is a recently described autoinflammatory condition presenting with intermittent fevers and mucocutaneous ulcerations. The RELA gene encodes the p65 protein, one of five NF-κB family transcription factors. As RELA is an essential regulator of mucosal homeostasis, haploinsufficiency leads to decreased NF-κB signaling which promotes TNF-driven mucosal apoptosis with impaired epithelial recovery. Thus far, only eight cases have been reported in the literature. Here, we report four families with three novel and one previously described pathogenic variant in RELA. These four families included 23 affected individuals for which genetic testing was available in 16. Almost half of these patients had been previously diagnosed with more common rheumatologic entities (such as Behcet's Disease; BD) prior to the discovery of their pathogenic RELA variants. The most common clinical features were orogenital ulcers, rash, joint inflammation, and fever. The least common were conjunctivitis and recurrent infections. Clinical variability was remarkable even among familial cases, and incomplete penetrance was observed. Patients in our series were treated with a variety of medications, and benefit was observed with glucocorticoids, colchicine, and TNF inhibitors. Altogether, our work adds to the current literature and doubles the number of reported cases with RELA-Associated Inflammatory Disease (RAID). It reaffirms the central importance of the NF-κB pathway in immunity and inflammation, as well as the important regulatory role of RELA in mucosal homeostasis. RELA associated inflammatory disease should be considered in all patients with BD, particularly those with early onset and/or with a strong family history.

Export metadata

Additional Services

Search Google Scholar Check availability

Statistics

Show usage statistics
Metadaten
Document Type:Article
Language:English
Author:Jason W. An, Pallavi Pimpale-Chavan, Deborah L. Stone, Marcia Bandeira, Fatma Dedeoglu, Jeffrey Lo, John Bohnsack, Sofia Rosenzweig, Oskar Schnappauf, Dilan Dissanayake, Linda T. Hiraki, Daniel L. Kastner, Christina Pelajo, Ronald M. Laxer, Ivona Aksentijevich
Parent Title (English):Frontiers in Immunology
Volume:14
Article Number:1127085
ISSN:1664-3224
DOI:https://doi.org/10.3389/fimmu.2023.1127085
PMID:https://pubmed.ncbi.nlm.nih.gov/36926348
Publisher:Frontiers Media
Date of first publication:2023/02/28
Keyword:Behcet’s Disease; NF-κB; RAID; RELA; RELA haploinsufficiency; RELA-associated inflammatory disease; autoinflammatory; mucosal ulcers
Departments, institutes and facilities:Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Entry in this database:2023/07/27