TY  - JOUR
U1  - Wissenschaftlicher Artikel
A1  - An, Jason W.
A1  - Pimpale-Chavan, Pallavi
A1  - Stone, Deborah L.
A1  - Bandeira, Marcia
A1  - Dedeoglu, Fatma
A1  - Lo, Jeffrey
A1  - Bohnsack, John
A1  - Rosenzweig, Sofia
A1  - Schnappauf, Oskar
A1  - Dissanayake, Dilan
A1  - Hiraki, Linda T.
A1  - Kastner, Daniel L.
A1  - Pelajo, Christina
A1  - Laxer, Ronald M.
A1  - Aksentijevich, Ivona
T1  - Case report: Novel variants in RELA associated with familial Behcet's-like disease
JF  - Frontiers in Immunology
N2  - 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.
KW  - NF-κB
KW  - mucosal ulcers
KW  - Behcet’s Disease
KW  - autoinflammatory
KW  - RAID
KW  - RELA haploinsufficiency
KW  - RELA-associated inflammatory disease
KW  - RELA
Y1  - 2023
SN  - 1664-3224
SS  - 1664-3224
U6  - https://doi.org/10.3389/fimmu.2023.1127085
DO  - https://doi.org/10.3389/fimmu.2023.1127085
PM  - 36926348
VL  - 14
PB  - Frontiers Media
ER  -