A5100433606- Immunodeficiency and Autoimmune Disorders
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- Diabetes and associated disorders
- interferon and immune responses
- Immune Response and Inflammation
- Blood disorders and treatments
- Traditional Chinese Medicine Analysis
- Natural product bioactivities and synthesis
- Inflammasome and immune disorders
- Phytochemistry and Biological Activities
- Chronic Lymphocytic Leukemia Research
- Long-Term Effects of COVID-19
- Respiratory viral infections research
- NF-κB Signaling Pathways
- Kawasaki Disease and Coronary Complications
- Cytomegalovirus and herpesvirus research
- Orthopedic Surgery and Rehabilitation
- RNA regulation and disease
- Pharmacological Effects of Natural Compounds
- Traditional Chinese Medicine Studies
- Platelet Disorders and Treatments
- Complement system in diseases
Kunming University of Science and Technology
2023-2025
National Institute of Allergy and Infectious Diseases
2015-2024
Zhejiang University
2005-2024
National Institutes of Health
2015-2024
Office of Extramural Research
2020-2024
Aviation General Hospital
2024
Beijing Institute of Technology
2024
Huazhong University of Science and Technology
2010-2023
Sun Yat-sen University
2023
Sichuan University
2010-2023
Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 987 patients with life-threatening disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), 13 types IFN-α (36), or both (52) onset critical disease; a few also auto-Abs other three type I IFNs. The neutralize ability corresponding IFNs to block...
The genetics underlying severe COVID-19 immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody dampens IFN response prevent damage from pathogen-induced inflammation. Two studies now examine likelihood affects risk of coronavirus disease 2019 (COVID-19) through components this (see Perspective by Beck Aksentijevich). Q....
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor found on immune cells. The consequences of mutations in CTLA4 humans are unknown. We identified germline heterozygous subjects with severe dysregulation from four unrelated families. Whereas Ctla4 mice have no obvious phenotype, human haploinsufficiency caused FoxP3(+) regulatory (Treg) cells, hyperactivation effector and lymphocytic infiltration target organs. Patients also exhibited progressive loss circulating B...
Trafficking from bedside to bench Typically in translational research, a discovery cell or molecular biology is later exploited improve patient care. Occasionally, information flows the opposite direction. Lo et al. found that patients with an autoimmune disorder caused by deficiency of protein called LRBA responded dramatically drug abatacept (see Perspective Sansom). Abatacept contains segment potent inhibitory immune receptor, CTLA4. Experiments prompted this observation revealed...
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found about 10% patients with critical COVID-19 pneumonia, but not subjects asymptomatic infections. We detect auto-Abs 100-fold lower, more physiological, (100 pg/mL, 1/10 dilutions plasma) 13.6% 3,595 COVID-19, including 21% 374 > 80 years, and 6.5% 522 severe COVID-19. These antibodies also detected 18% the 1,124 deceased (aged 20 days-99 years; mean: 70...
Class IA phosphatidylinositol 3-kinases (PI3K), which generate PIP3 as a signal for cell growth and proliferation, exist an intracellular complex of catalytic subunit bound to regulatory subunit. We others have previously reported that heterozygous mutations in PIK3CD encoding the p110δ PI3K cause unique disorder termed p110δ-activating causing senescent T cells, lymphadenopathy, immunodeficiency (PASLI) disease. report four patients from three families with similar disease who harbor...
Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It important to estimate their quantitative impact on mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence these risk death increase with higher in men. Using an unvaccinated sample 1,261 deceased patients 34,159 individuals from general population, we found against IFNs strongly increased...
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 five unrelated with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing generate 2′-5′-linked oligoadenylates (2-5A) activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines primary myeloid cells OAS1, OAS2, RNase produce excessive amounts cytokines upon dsRNA acute...
Abstract The chr12q24.13 locus encoding OAS1–OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this in relation to COVID-19 severity. In our analysis of patients European ( n = 2,249) African 835) ancestries hospitalized versus nonhospitalized COVID-19, the risk was a common OAS1 haplotype, which also reduced severe acute respiratory syndrome 2 (SARS-CoV-2) clearance trial...
Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent interferon (IFN) immunity or autoantibodies against IFN, account for 15–20% cases life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants remain be identified ~ 80% cases. Methods report here a genome-wide rare variant burden association analysis 3269 patients with COVID-19, 1373 SARS-CoV-2-infected individuals without pneumonia. Among 928...
Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development targeted therapies.
In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)–related diseases. Three presented EBV-associated Hodgkin’s lymphoma and hypogammaglobulinemia; one also had severe varicella infection. The fourth viral encephalitis during infancy. Homozygous frameshift or in-frame deletions in CD70 these abolished either surface expression binding its cognate...
MDA5 is a cytosolic sensor of double-stranded RNA (ds)RNA including viral byproducts and intermediates. We studied child with life-threatening, recurrent respiratory tract infections, caused by viruses human rhinovirus (HRV), influenza virus, syncytial virus (RSV). identified in her homozygous missense mutation IFIH1 that encodes MDA5. Mutant was expressed but did not recognize the synthetic agonist/(ds)RNA mimic polyinosinic-polycytidylic acid. When overexpressed, mutant failed to drive...
Life-threatening “breakthrough” cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie least 15% pneumonia unvaccinated individuals; their contribution hypoxemic breakthrough vaccinated people is unknown. We studied a cohort 48 (aged 20 86 years) who received two doses messenger RNA (mRNA) vaccine and developed infection with 2 weeks 4 months later. Ab levels...
Phosphatidylinositol 3-kinase-gamma (PI3Kγ) is highly expressed in leukocytes and an attractive drug target for immune modulation. Different experimental systems have led to conflicting conclusions regarding inflammatory anti-inflammatory functions of PI3Kγ. Here, we report a human patient with bi-allelic, loss-of-function mutations PIK3CG resulting absence the p110γ catalytic subunit She has history childhood-onset antibody defects, cytopenias, T lymphocytic pneumonitis colitis, reduced...