A5057205976- Rheumatoid Arthritis Research and Therapies
- Systemic Lupus Erythematosus Research
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Viral Infections and Immunology Research
- Autoimmune and Inflammatory Disorders Research
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Systemic Sclerosis and Related Diseases
- Cancer Immunotherapy and Biomarkers
- Peptidase Inhibition and Analysis
- HER2/EGFR in Cancer Research
- Inflammatory Myopathies and Dermatomyositis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Vector-borne infectious diseases
- Immune cells in cancer
- Mast cells and histamine
- vaccines and immunoinformatics approaches
- Cytokine Signaling Pathways and Interactions
- Vasculitis and related conditions
Johns Hopkins Medicine
2016-2025
Johns Hopkins University
2016-2025
Stanford University
2024
Development Fund
2024
University of Baltimore
2017-2023
AstraZeneca (United States)
2022
University of Alabama at Birmingham
2022
Hospital for Special Surgery
2022
Cornell University
2022
Columbia University
2022
Autoimmune diseases are thought to be initiated by exposures foreign antigens that cross-react with endogenous molecules. Scleroderma is an autoimmune connective tissue disease in which patients make antibodies a limited group of autoantigens, including RPC1, encoded the POLR3A gene. As scleroderma and against RPC1 at increased risk for cancer, we hypothesized "foreign" this somatically mutated genes patients' incipient cancers. Studying cancers from patients, found genetic alterations locus...
RA-associated hypercitrullination is specifically induced by immune-mediated membrane pore-forming pathways.
Multiple Sclerosis (MS) is characterized by central nervous system perivenular and parenchymal mononuclear cell infiltrates consisting of activated T cells macrophages. We recently demonstrated that elevated expression the voltage-gated potassium channel, Kv1.3, a functional marker effector memory (T EM ) in experimental allergic encephalomyelitis myelin-specific derived from peripheral blood patients with MS. Herein, we show Kv1.3 highly expressed postmortem MS brain inflammatory...
Objective To define the relationship between autoantigen citrullination and different peptidylarginine deiminase (PAD) enzymes in rheumatoid arthritis (RA). Methods Citrullinated autoantigens were identified by immunoblotting control ionomycin-activated human primary neutrophil lysate with RA sera. Autoantigen identity sites defined mass spectrometry. PAD isoenzyme expression neutrophils was determined immunoblotting. substrate specificity addressed HL-60 cell lysates co-incubated...
Autoantibodies from rheumatoid arthritis patients augment the function of PAD4 by decreasing its calcium requirement.
To address mechanisms that control the activity of human peptidyl arginine deiminase type 4 (PAD-4).PAD-4 autocitrullination was determined by anti-modified citrulline immunoblotting, using purified recombinant and endogenous PAD-4 from activated primary neutrophils cell lines expressing PAD-4. The citrullination sites in were mass spectrometry. Mechanisms autocitrullination-induced inactivation functional consequences polymorphic variants addressed components wild-type, mutant, relevant to...
To determine whether antibodies against peptidyl arginine deiminase type 4 (PAD-4) are present in the preclinical phase of rheumatoid arthritis (RA) and to compare timing extent their appearance with those other autoantibodies.Prediagnosis serum samples from 83 patients RA were evaluated for presence anti-PAD-4 antibody, anti-cyclic citrullinated peptide (anti-CCP) factor. In addition, a control cohort (n = 83) matched by age, sex, race, number samples, duration storage was tested antibody...
For almost 20 years, apoptosis and secondary necrosis have been considered the major source of autoantigens endogenous adjuvants in pathogenic model systemic autoimmune diseases. This focus is justified part because initial evidence lupus erythematosus (SLE) guided investigators toward study apoptosis, but also other forms cell death were unknown. To date, it known that many occur, they vary their capacity to stimulate as well inhibit immune system. Among these, NETosis (an antimicrobial...
Autoantibodies directed against citrullinated epitopes of proteins are highly diagnostic rheumatoid arthritis (RA), and elevated levels protein citrullination can be found in the joints patients with RA. Calcium-dependent peptidyl-arginine deiminases (PAD) enzymes responsible for citrullination. PAD2 PAD4 enriched neutrophils likely drive under inflammatory conditions. PADs may released during NETosis or cell death, but mechanisms PAD activity physiological conditions have not been fully...
Abstract Cryptic peptides, hidden from the immune system under physiologic conditions, are revealed by changes to MHC class II processing and hypothesized drive loss of tolerance self-antigens in autoimmunity. Rheumatoid arthritis (RA) is an autoimmune disease characterized responses citrullinated self-antigens, which arginine residues converted citrullines. Here, we investigate hypothesis that citrullination exposes cryptic peptides modifying protein structure proteolytic cleavage. We show...
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with dramatic sex bias, affecting 9-times more women than men. Activation of toll-like receptor 7 (TLR7) by self-RNA central pathogenic process leading to aberrant production type-I interferon (IFN) in SLE, but the specific RNA molecules that serve as TLR7 ligands have not been defined. We therefore sought identify female-specific endogenous RNAs containing canonical stimulatory motifs. By leveraging gene expression data and...
Abstract Objective Protein citrullination is an important posttranslational modification recognized by rheumatoid arthritis (RA)–specific autoantibodies. One of the citrullinating enzymes, peptidyl arginine deiminase type 4 (PAD‐4), genetically associated with development RA in some populations, although mechanism(s) mediating this effect are not yet clear. There have been descriptions anti–PAD‐4 autoantibodies different rheumatic diseases. This study was undertaken to investigate whether...
Background A subset of rheumatoid arthritis (RA) patients have detectable antibodies directed against the peptidyl-arginine deiminase (PAD) enzyme isoforms 3 and 4. Anti-PAD3/4 cross-reactive (anti-PAD3/4XR) been shown to lower calcium threshold required for PAD4 activation, an effect potentially relevant pathogenesis RA-associated interstitial lung disease (ILD). Methods RA underwent multi-detector computed tomography (MDCT) chest with interpretation by a pulmonary radiologist ILD features....
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...
Objective Autoantibodies targeting peptidylarginine deiminase 4 (PAD4), an enzyme involved in protein citrullination, are found a subset of rheumatoid arthritis (RA) patients with severe joint disease. However, the mechanisms by which anti‐PAD4 antibodies participate disease pathogenesis incompletely defined. Methods We investigated role monoclonal derived from RA using collagen‐induced (CIA) mouse model and human monocyte vitro cultures. The cellular targets were identified knee cells...
Systemic lupus erythematosus (SLE) displays a hallmark interferon (IFN) signature. Yet, clinical trials targeting type I IFN (IFN-I) have shown variable efficacy, and blocking IFN-II failed to treat SLE. Here, we show that levels in SLE vary significantly across transcriptional endotypes. Whereas skin involvement correlated with IFN-I alone, systemic features like nephritis associated co-elevation of IFN-I, IFN-II, IFN-III, indicating additive effects severe Notably, while high IFN-II/-III...
Objectives: Peptidylarginine deiminases (PAD) 2 and 4 are key enzymes in rheumatoid arthritis (RA) pathogenesis due to their ability generate the protein targets of anti-citrullinated antibodies (ACPA). Anti-PAD4 that cross-react with PAD3 (anti-PAD3/4) have been identified associated severe joint lung disease. Here, we examined whether anti-PAD2 were present patients RA defined clinical significance. Patients Methods: A PAD2 ELISA was established screen for IgG sera from a prospective...
Evidence suggests that the presence of peptidyl arginine deiminase type 4 (PAD4) antibodies is associated with radiographic-severity rheumatoid arthritis (RA) among Caucasian patients. The anti-PAD4 were cross-reactivity against PAD3 was more aggressive erosive disease (compared without anti-PAD3 crossreactivity) in RA objectives this study to determine prevalence serum and anti-PAD4/PAD3 cross-reactive autoantibodies African Americans whether these associate radiographic severity...