A5048259074- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Malaria Research and Control
- Cytomegalovirus and herpesvirus research
- Diabetes and associated disorders
- Cytokine Signaling Pathways and Interactions
- Chemokine receptors and signaling
- Phagocytosis and Immune Regulation
- HIV Research and Treatment
- vaccines and immunoinformatics approaches
- Complement system in diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Inflammasome and immune disorders
- Respiratory viral infections research
- Salivary Gland Disorders and Functions
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- Intensive Care Unit Cognitive Disorders
Emory University
2013-2024
Center for Human Genetics
2021
Center for Rheumatology
2021
University of Rochester Medical Center
2014
University of Rochester
2005-2013
University of Chicago
2000
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 )....
While immunologic correlates of COVID-19 have been widely reported, their associations with post-acute sequelae (PASC) remain less clear. Due to the wide array PASC presentations, understanding if specific disease features associate discrete immune processes and therapeutic opportunities is important. Here we profile patients in recovery phase via proteomics screening machine learning find signatures ongoing antiviral B cell development, immune-mediated fibrosis, markers death but not...
Although B cells expressing the IFNγR or IFNγ-inducible transcription factor T-bet promote autoimmunity in Systemic Lupus Erythematosus (SLE)-prone mouse models, role for IFNγ signaling human antibody responses is unknown. We show that elevated levels of SLE patients correlate with expansion IgDnegCD27negCD11c+CXCR5neg (DN2) pre-antibody secreting cell (pre-ASC) subset. demonstrate naïve form T-bethi pre-ASCs following stimulation either Th1 IFNγ, IL-2, anti-Ig and TLR7/8 ligand IL-21...
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....
9G4(+) IgG Abs expand in systemic lupus erythematosus (SLE) a disease-specific fashion and react with different Ags including B cell apoptotic cells. Their shared use of VH4-34 represents unique system to understand the molecular basis autoreactivity. In this study, large panel recombinant mAbs from single naive memory cells was generated tested against cells, other Ags. Mutagenesis eliminated framework-1 hydrophobic patch (HP) responsible for 9G4 idiotype. The expression HP unselected...
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...
Objective The significance of distinct B cell abnormalities in primary Sjögren's syndrome (SS) remains to be established. We undertook this study analyze the phenotype and messenger RNA (mRNA) transcript profiles subsets patients with SS compare them those sicca healthy controls. Methods CD19+ cells from 26 SS, 27 patients, 22 controls were analyzed by flow cytometry. Gene expression purified (from 3–5 subjects per group test) using Affymetrix gene arrays. Results Patients had lower...
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.
ABSTRACT Pre-existing anti-interferon alpha (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α the airways – initial site of infection can also determine disease outcomes. In this study, we developed a new multiparameter technology, flowBEAT, quantify and profile isotypes anti-SARS-CoV-2 antibodies longitudinal samples collected over 20 months from airway matching 129 donors mild, moderate, severe We...
Abstract We have used TCR transgenic mice directed to different MHC class II-restricted determinants from the influenza virus hemagglutinin (HA) analyze how specificity for self-peptides can shape CD4+CD25+ regulatory T (Treg) cell formation. show that substantial increases in number of Treg cells occur when an autoreactive a major I-Ed-restricted determinant HA develops expressing as self-Ag, and efficiency this process is largely unaffected by ability coexpress additional α-chains. This...
Abstract Immunodominance refers to the restricted peptide specificity of T cells that are detectable after an adaptive immune response. For CD4 cells, many mechanisms used explain this selectivity suggest events related Ag processing play a major role in determining peptide’s ability recruit cells. Implicit these models is prediction molecular context which antigenic contained will impact significantly on its immunodominance. In study, we present evidence cell responses peptides within...