A5043889746- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- Long-Term Effects of COVID-19
- Immune Cell Function and Interaction
- Respiratory viral infections research
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Pneumonia and Respiratory Infections
- Hematological disorders and diagnostics
- Systemic Lupus Erythematosus Research
- Bacterial Infections and Vaccines
- Asthma and respiratory diseases
- Influenza Virus Research Studies
- Diabetes and associated disorders
- Streptococcal Infections and Treatments
- Erythrocyte Function and Pathophysiology
- Calcium signaling and nucleotide metabolism
- Immunodeficiency and Autoimmune Disorders
- Heparin-Induced Thrombocytopenia and Thrombosis
- Immune responses and vaccinations
- Complement system in diseases
- Malaria Research and Control
- Pancreatic function and diabetes
- SARS-CoV-2 detection and testing
Emory University
2014-2024
Emory University Hospital
2016
University of Rochester Medical Center
2010
Pulmonary and Critical Care Associates
2008
A wide spectrum of clinical manifestations has become a hallmark the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although immunological underpinnings diverse disease outcomes remain to be defined. We performed detailed characterization B cell responses through high-dimensional flow cytometry reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks extrafollicular activation shared...
Abstract Severe SARS-CoV-2 infection 1 has been associated with highly inflammatory immune activation since the earliest days of COVID-19 pandemic 2–5 . More recently, these responses have emergence self-reactive antibodies pathologic potential 6–10 , although their origins and resolution remained unclear 11 Previously, we others identified extrafollicular B cell activation, a pathway formation new autoreactive in chronic autoimmunity 12,13 as dominant feature severe critical (refs. 14–18 )....
Abstract Human antibody-secreting cells (ASC) in peripheral blood are found after vaccination or infection but rapidly apoptose unless they migrate to the bone marrow (BM). Yet, elements of BM microenvironment required sustain long-lived plasma (LLPC) remain elusive. Here, we identify factors that maintain human ASC > 50 days vitro. The critical components cell-free vitro mimic consist products from primary mesenchymal stromal (MSC), a proliferation-inducing ligand (APRIL), and hypoxic...
Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibody types, some of which are produced long-lived plasma cells (LLPC). Active SLE generates increased circulating antibody-secreting (ASC). Here, we examine the phenotypic, molecular, structural, and functional features ASC in SLE. Relative to post-vaccination healthy controls, blood from patients with active enriched newly generated mature CD19 − CD138 + ASC, similar bone marrow LLPC....
Abstract An emerging feature of COVID-19 is the identification autoreactivity in patients with severe disease that may contribute to pathology, however origin and resolution these responses remain unclear. Previously, we identified strong extrafollicular B cell activation as a shared immune response between both advanced rheumatic disease. In autoimmune settings, this pathway associated relaxed peripheral tolerance antibody secreting compartment generation de novo autoreactive responses....
Abstract/Introduction A wide clinical spectrum has become a hallmark of the SARS-CoV-2 (COVID-19) pandemic, although its immunologic underpinnings remain to be defined. We have performed deep characterization B cell responses through high-dimensional flow cytometry reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks extrafollicular activation as previously described autoimmune settings. Extrafollicular...
Human antibody-secreting cells (ASCs) triggered by immunization are globally recognized as CD19loCD38hiCD27hi. Yet, different vaccines give rise to antibody responses of longevity, suggesting ASC populations heterogeneous. We define circulating-ASC heterogeneity in vaccine using multicolor flow cytometry, morphology, VH repertoire, and RNA transcriptome analysis. also tested differential survival a human cell-free system that mimics the bone marrow (BM) microniche. In peripheral blood, we...
Immunoglobulin (Ig) E is central to the pathogenesis of allergic conditions, including fungal rhinosinusitis. However, little known about IgE antibody secreting cells (ASCs). We performed single-cell RNA sequencing from cluster differentiation (CD)19+ and CD19− ASCs nasal polyps patients with rhinosinusitis (n = 3). Nasal were highly enriched in CD19+ ASCs. Class-switched IgG IgA dominant (95.8%), whereas rare (2%) found only compartment. Through Ig gene repertoire analysis, shared clones...
Abstract SARS-CoV-2 has caused over 100,000,000 cases and almost 2,500,000 deaths globally. Comprehensive assessment of the multifaceted antiviral Ab response is critical for diagnosis, differentiation severity, characterization long-term immunity, especially as COVID-19 vaccines become available. Severe disease associated with early, massive plasmablast responses. We developed a multiplex immunoassay from serum/plasma acutely infected convalescent patients prepandemic postpandemic healthy...
ABSTRACT Post-acute sequelae of SARS-CoV-2 (SARS2) infection (PASC) is a heterogeneous condition, but the main viral drivers are unknown. Here, we use MENSA, Media Enriched with Newly Synthesized Antibodies, secreted exclusively from circulating human plasmablasts, to provide an immune snapshot that defines underlying triggers. We proof-of-concept testing MENSA technology can capture new host response accurately diagnose acute primary and breakthrough infections when known SARS2 virus or...
Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well contribution of disease-induced abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and analysis patients with autoimmune systemic lupus erythematosus (SLE) who received Wuhan-Hu-1 monovalent disease 2019 vaccine. Our findings revealed that SLE...
Infections with human rhinovirus (HRV) are commonly associated acute upper and lower respiratory tract disease asthma exacerbations. The role that HRVs play in these diseases suggests it is important to understand host-specific or virus-specific factors contribute pathogenesis. Since species A often more serious HRV than B HRVs, differences immune responses they induce should inform To identify induced responses, we evaluated 3 viruses, 25, 31 36 4, 35 48 by exposing PBMCs infected Calu-3...
Ab-producing plasma cells (PCs) serve as key participants in countering pathogenic challenges well being contributors to autoimmune and malignant disorders. Thus far, only a limited number of PC-specific markers have been identified. The characterization the unique variable lymphocyte receptor (VLR) Abs that are made by evolutionarily distant jawless vertebrates prompted us investigate whether VLR could detect novel PC antigens not recognized conventional Abs. Here, we describe monoclonal...
Plasmodium relapses are attributed to the activation of dormant liver-stage parasites and responsible for a significant number recurring malaria blood-stage infections. While characteristic human infections caused by P. vivax ovale, their relative contribution disease burden transmission remains poorly understood. This is largely because it difficult identify 'bona fide' relapse due ongoing in most endemic areas. Here, we use cynomolgi–rhesus macaque model relapsing demonstrate that clinical...
Abstract Novel mRNA vaccines have resulted in a reduced number of SARS-CoV-2 infections and hospitalizations. Yet, there is paucity studies regarding their effectiveness on immunocompromised autoimmune subjects. In this study, we enrolled subjects naïve to from two cohorts healthy donors (HD, n=56) systemic lupus erythematosus (SLE, n=69). Serological assessments circulating antibodies revealed significant reduction potency breadth neutralization the SLE group, only partially rescued by 3 rd...
Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibodies, some of which are present in high titers a sustained, B cell-independent fashion consistent with their generation from long-lived plasma cells (LLPC). Active SLE displays numbers circulating antibody-secreting (ASC). Understanding the mechanisms and survival ASC would contribute important insight into pathogenesis novel targeted therapies. We studied properties through systematic analysis...
SARS-CoV-2 has caused over 36,000,000 cases and 1,000,000 deaths globally. Comprehensive assessment of the multifaceted anti-viral antibody response is critical for diagnosis, differentiation severe disease, characterization long-term immunity. Initial observations suggest that disease associated with higher levels greater B cell/plasmablast responses. A multi-antigen immunoassay to define complex serological landscape clinical associations essential. We developed a multiplex evaluated...
Abstract Isolating cells based on their secreted proteins remain a challenge. The authors demonstrate capacity for high throughput single‐cell protein secretion analysis and isolation heterofunctional particles combined with fluorescence activated cell sorting (FACS). workflow shows that antibody secreting (ASCs) specific the H1 from influenza virus can be isolated B cells. consists of incubating anti‐CD27 ASCs, capturing locally immunoglobulins Protein G particles, identifying to via...
Background Streptococcus pneumoniae infections cause morbidity and mortality worldwide. A rapid, simple diagnostic method could reduce the time needed to introduce definitive therapy potentially improving patient outcomes. Methods We two new methods for diagnosing S . by measuring presence of newly activated, pathogen-specific, circulating Antibody Secreting Cells (ASC). First, ASC were detected ELISpot assays that measure cells secreting antibodies specific signature antigens. Second,...