Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F23%3A10471080" target="_blank" >RIV/00064203:_____/23:10471080 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/23:00133819 RIV/00216208:11130/23:10471080

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=XG9naz4bp5" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=XG9naz4bp5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41586-023-06717-x" target="_blank" >10.1038/s41586-023-06717-x</a>

Result language

angličtina

Original language name

Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency

Original language description

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs)(1,2), conferring a predisposition to life-threatening COVID-19 pneumonia(3). 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(LOF)/IκBδ(GOF)). By contrast, neutralizing autoantibodies against type I IFNs are not found in individuals who are heterozygous for NFKB2 variants causing haploinsufficiency of p100 and p52 (hereafter, p52(LOF)/IκBδ(LOF)) or gain-of-function of p52 (hereafter, p52(GOF)/IκBδ(LOF)). 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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30102 - Immunology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nature

ISSN

0028-0836

e-ISSN

1476-4687

Volume of the periodical

623

Issue of the periodical within the volume

7988

Country of publishing house

GB - UNITED KINGDOM

Number of pages

11

Pages from-to

803-813

UT code for WoS article

001182780400001

EID of the result in the Scopus database

2-s2.0-85176091832