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Article
Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency
The linear ubiquitin assembly complex (LUBAC) consists of HOIP, HOIL-1 and SHARPIN and is essential for proper immune responses. Individuals with HOIP and HOIL-1 deficiencies present with severe immunodeficien...
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Article
Open AccessCorrection: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
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Article
Open AccessAutoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency
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 t...
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Article
Novel NF-kappa B Inhibitor Alpha Gain-of-Function Variant in an Infant with Lymphocytosis and Recurrent Serratia Bacteremia
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Article
Open AccessInherited ARPC5 mutations cause an actinopathy impairing cell motility and disrupting cytokine signaling
We describe the first cases of germline biallelic null mutations in ARPC5, part of the Arp2/3 actin nucleator complex, in two unrelated patients presenting with recurrent and severe infections, early-onset aut...
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Article
Open AccessRare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases ...
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Article
SCID and Other Inborn Errors of Immunity with Low TRECs — the Brazilian Experience
Severe combined immunodeficiency, SCID, is a pediatric emergency that represents the most critical group of inborn errors of immunity (IEI). Affected infants present with early onset life-threatening infection...
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Article
Open AccessX-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia
Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is in...
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Article
Inherited PD-1 deficiency underlies tuberculosis and autoimmunity in a child
The pathophysiology of adverse events following programmed cell death protein 1 (PD-1) blockade, including tuberculosis (TB) and autoimmunity, remains poorly characterized. We studied a patient with inherited ...
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Article
EDA-ID: a Severe Clinical Presentation Associated with a New IKBKG Mutation
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Article
A variant in human AIOLOS impairs adaptive immunity by interfering with IKAROS
In the present study, we report a human-inherited, impaired, adaptive immunity disorder, which predominantly manifested as a B cell differentiation defect, caused by a heterozygous IKZF3 missense variant, resulti...
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Article
Inherited TOP2B Mutation: Possible Confirmation of Mutational Hotspots in the TOPRIM Domain
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Article
The genetic basis of pneumococcal and staphylococcal infections: inborn errors of human TLR and IL-1R immunity
Many bacteria can cause pyogenic lesions in humans. Most of these bacteria are harmless in most individuals, but they, nevertheless, cause significant morbidity and mortality worldwide. The inherited and acqui...
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Article
Autoimmune Lymphoproliferative Syndrome Presenting with Invasive Streptococcus pneumoniae Infection
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Article
Human DOCK2 Deficiency: Report of a Novel Mutation and Evidence for Neutrophil Dysfunction
DOCK2 is a guanine-nucleotide-exchange factor for Rac proteins. Activated Rac serves various cellular functions including the reorganization of the actin cytoskeleton in lymphocytes and neutrophils and product...
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Article
An essential role for the Zn2+ transporter ZIP7 in B cell development
Despite the known importance of zinc for human immunity, molecular insights into its roles have remained limited. Here we report a novel autosomal recessive disease characterized by absent B cells, agammaglobu...
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Article
Human hyper-IgE syndrome: singular or plural?
Spectacular progress has been made in the characterization of human hyper-IgE syndrome (HIES) over the last 50 years. HIES is a primary immunodeficiency defined as an association of atopy in a context of very ...
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Article
Human IκBα Gain of Function: a Severe and Syndromic Immunodeficiency
Germline heterozygous gain-of-function (GOF) mutations of NFKBIA, encoding IκBα, cause an autosomal dominant (AD) form of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). Fourteen unrelated patient...
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Article
Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery
Joseph Gleeson and colleagues report whole-exome sequencing of a cohort of over 1,000 individuals from the Greater Middle East, characterizing common and rare variants. They find evidence of subregional divers...
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Article
The mutation significance cutoff: gene-level thresholds for variant predictions
