Universidad del Desarrollo

Now showing 1 - 3 of 3

Some of the metrics are blocked by your
consent settings
Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency
(2023)
Tom Le Voyer
;
Audrey V. Parent
;
Xian Liu
;
Axel Cederholm
;
Adrian Gervais
<jats:title>Abstract</jats:title><jats:p>Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs)<jats:sup>1,2</jats:sup>, conferring a predisposition to life-threatening COVID-19 pneumonia<jats:sup>3</jats:sup>. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52<jats:sup>LOF</jats:sup>/IκBδ<jats:sup>GOF</jats:sup>). By contrast, neutralizing autoantibodies against type I IFNs are not found in individuals who are heterozygous for <jats:italic>NFKB2</jats:italic> variants causing haploinsufficiency of p100 and p52 (hereafter, p52<jats:sup>LOF</jats:sup>/IκBδ<jats:sup>LOF</jats:sup>) or gain-of-function of p52 (hereafter, p52<jats:sup>GOF</jats:sup>/IκBδ<jats:sup>LOF</jats:sup>). In contrast to patients with APS-1, patients with disorders of NIK, RELB or NF-κB2 have very few tissue-specific autoantibodies. However, their thymuses have an abnormal structure, with few AIRE-expressing medullary thymic epithelial cells. Human inborn errors of the alternative NF-κB pathway impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases.</jats:p>
3Scopus© Citations 90
Some of the metrics are blocked by your
consent settings
Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children
(2023)
Danyel Lee
;
Jérémie Le Pen
;
Ahmad Yatim
;
Beihua Dong
;
Yann Aquino
<jats:p> Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of <jats:italic>OAS1</jats:italic> , <jats:italic>OAS2</jats:italic> , or <jats:italic>RNASEL</jats:italic> in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L–deficient cells. Cytokine production in RNase L–deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C. </jats:p>
11Scopus© Citations 137
Some of the metrics are blocked by your
consent settings
Coronavirus disease 2019 in patients with inborn errors of immunity: An international study
(2021)
Isabelle Meyts
;
Giorgia Bucciol
;
Isabella Quinti
;
Bénédicte Neven
;
Alain Fischer
Scopus© Citations 309 3

CRIS

Browse

Filters

Settings

Sort By

Results per page

Search Results