A5045495959- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Long-Term Effects of COVID-19
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- Diabetes and associated disorders
- Cytokine Signaling Pathways and Interactions
- SARS-CoV-2 detection and testing
- Immune Response and Inflammation
- interferon and immune responses
- Asthma and respiratory diseases
- Lymphoma Diagnosis and Treatment
- International Development and Aid
- Global Financial Crisis and Policies
- Allergic Rhinitis and Sensitization
- Healthcare Systems and Technology
- Mast cells and histamine
- Kawasaki Disease and Coronary Complications
- Chronic Lymphocytic Leukemia Research
- Clinical practice guidelines implementation
- Cancer Immunotherapy and Biomarkers
Emory University
2018-2024
Center for Economic and Policy Research
2023
Center for Rheumatology
2020-2021
Center for Human Genetics
2021
University of Alabama at Birmingham
2010-2016
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 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...
Abstract Anti-dsDNA antibodies are pathogenically heterogeneous, implying distinct origins and antigenic properties. Unexpectedly, during the clinical molecular characterization of autoantibodies to endonuclease DNase1L3 in patients with systemic lupus erythematosus (SLE), we identified a subset neutralizing anti-DNase1L3 previously catalogued as anti-dsDNA. Based on their variable heavy-chain (V H ) gene usage, these can be divided two groups. One group is encoded by inherently autoreactive...
Type I IFNs (IFN-α and IFN-β) type II IFN (IFN-γ) mediate both regulation inflammation in multiple sclerosis, neuromyelitis optica, experimental autoimmune encephalomyelitis (EAE). However, the underlying mechanism for these Janus-like activities of neuroinflammation remains unclear. Although endogenous signaling provides a protective response neuroinflammation, we find that when IFN-γ is ablated, drive inflammation, resulting exacerbated EAE. has disease stage-specific opposing function...
Abstract Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those mild and severe disease, but IgG only in disease. A similar pattern was observed a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from COVID-19.
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...
While the contribution of B-cells to SLE is well established, its role in chronic cutaneous lupus erythematosus (CCLE) remains unclear. Here, we compare B-cell and serum auto-antibody profiles between patients with systemic (SLE), CCLE, overlap conditions.
Inhibitors of glycogen synthase kinase 3 (GSK3) are being explored as therapy for chronic inflammatory diseases. We previously demonstrated that the GSK inhibitor lithium is beneficial in experimental autoimmune encephalomyelitis (EAE), mouse model multiple sclerosis. In this study we report suppresses EAE induced by encephalitogenic interferon-γ (IFN-γ)-producing T helper (Th1) cells but not interleukin (IL)-17-producing (Th17) cells. The therapeutic activity required functional...
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...
Most genetic variants that confer risk of complex immune-mediated diseases (IMD) affect gene regulation in specific cell types. Their target genes and focus types are often unknown, partially because some effects hidden untested states. B cells play important roles IMDs, including autoimmune, allergic, infectious, cancerous diseases. However, despite this established importance, activation states underrepresented functional genomics studies. In study, we obtained from 26 healthy female...
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...
Mechanisms that modulate the generation of Th17 cells are incompletely understood. We report activation casein kinase 2 (CK2) by CD5 is essential for efficient in vitro and vivo. In our study, CD5–CK2 signaling pathway enhanced TCR‐induced AKT promoted differentiation two independent mechanisms: inhibition glycogen synthase 3 (GSK3) mTOR. Genetic ablation attenuated consequently increased activity GSK3 cells. This resulted sensitivity to IFN‐γ‐mediated inhibition. absence CD5‐CK2 signaling,...
CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T B1a lymphocytes. Current data support the view that negative regulator of antigen-specific receptor-mediated signaling in these cells, this would likely be achieved through interaction with ligand/s (CD5L) still undefined nature immune or accessory cells. To determine functional consequence loss CD5/CD5L vivo, new transgenic mouse line was generated (shCD5EμTg), expressing circulating...
CD5 is well recognized for its importance in thymic selection. Although this property of has been attributed to ITIM-domain dependent regulation TCR-signal strength, the mechanism not established. A second major signaling domain within cytoplasmic tail a CK2 binding/activation (CD5-CK2BD). Using gene-targeted mouse which CD5-CK2BD selectively ablated (CD5-ΔCK2BD), we determined that loss function CD5-CK2 MHC-II selecting TCR transgenic (OT-II) resulted decrease double positive (DP)...
Background: Accurate serological assays can improve the early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but few studies have compared performance characteristics between in symptomatic and recovered patients. Methods: We recruited 32 patients who had 2019 disease (COVID-19; 18 hospitalized actively symptomatic, 14 mild cases), measured levels IgM (against full-length S1 or highly homologous SARS-CoV E protein) IgG receptor binding domain [RBD])....