Kurumun Atıf Alan Makalesi
Atıf Alan Yayın
Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children
Scopus
Open Access Toplam 142 atıf DOI
Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL 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.
Atıf Kaynağı
Atıf Yapan Yayın
Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection
Scopus
Havuzumuzda Open Access 8 atıf almış
Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.
Atıf Yapan Makale Bilgileri
Kurumlar (22)
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland
École Polytechnique Fédérale de Lausanne
Lausanne, Switzerland
Garvan Institute of Medical Research
Sydney, Australia
Helix OpCo LLC
San Diego, United States
Hôpital Bichat-Claude-Bernard AP-HP
Paris, France
Hôpital Necker Enfants Malades
Paris, France
Hôpital Universitaire Pitié Salpêtrière
Paris, France
Howard Hughes Medical Institute
Chevy Chase, United States
hVIVO Services Limited
London, United Kingdom
Imperial College London
London, United Kingdom