Abstract Number: L08 • ACR Convergence 2023
Early Clinical Development of CIT-013, a First in Class NETosis Inhibitor, in a Randomized Phase I Dose Escalation Study in Healthy Volunteers Demonstrating Potent Inhibition of LPS Induced Neutrophil Extracellular Trap Formation
Background/Purpose: Aberrant Neutrophil Extracellular Traps (NETs) production contributes to the pathophysiology of multiple inflammatory and autoimmune diseases such as Rheumatoid arthritis (RA) Hidradenitis suppurativa (HS),…Abstract Number: 0045 • ACR Convergence 2023
Discovery and Characterization of a Selective, Orally Bioavailable PAD4 Inhibitor to Target NETs Driven Autoimmune and Inflammatory Diseases
Background/Purpose: Protein arginine deiminases (PAD) 4 is an enzyme that catalyzes the conversion of protein-embedded arginine to citrulline. It is essential for neutrophil extracellular traps…Abstract Number: 0050 • ACR Convergence 2023
Anti-Citrullinated Histone Antibody CIT-013, a Dual Action Therapeutic for Neutrophil Extracellular Trap Associated Autoimmune Disease
Background/Purpose: Neutrophil extracellular traps (NETs) contribute to the pathophysiology of multiple inflammatory and autoimmune diseases (Chirivi et al., 2021; DOI: 10.1038/s41423-020-0381-3). Targeting the NETosis pathway…Abstract Number: 0423 • ACR Convergence 2023
Detection of Citrullinated Proteins Recognized by a Novel Chimeric Antigen Receptor TregTherapy in Both Synovial Fluid and Serum from Patients with Rheumatoid Arthritis
Background/Purpose: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases and despite many therapeutic options, an unmet medical need persists for novel therapies…Abstract Number: 1727 • ACR Convergence 2023
Arthritogenicity of Homocitrullinated Peptides in HLA-DRB1 Transgenic Mice
Background/Purpose: Most rheumatoid arthritis (RA) patients express autoantibodies to post-translationally modified antigens, including citrullinated and homocitrullinated (also known as carbamylated) peptides. Homocitrulline and citrulline are…Abstract Number: 1742 • ACR Convergence 2023
Sputum Citrullinated Proteins and Sputum Anti-Cit-S100A8/A9 IgG Antibodies Are Increased in Serum Anti-CCP-IgG Positive Individuals Who Developed RA
Background/Purpose: The presence of anti-CCP-IgG in the blood identifies individuals who are "at-risk" of developing RA. Our group has reported that in a cohort of…Abstract Number: 1748 • ACR Convergence 2023
Macrophage Extracellular Traps Require Peptidylarginine Deiminase 2 and 4 and Are a Source of Citrullinated Antigens Bound by Rheumatoid Arthritis Autoantibodies
Background/Purpose: Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis, but the sources of citrullinated antigens as well as which peptidylarginine deiminases (PADs) are…Abstract Number: 1764 • ACR Convergence 2023
Antibody Responses to Citrullinated Type II Collagen and Vimentin Modified with Malondialdehyde-Acetaldehyde Differ in Rheumatoid Arthritis and Rheumatoid Arthritis-Interstitial Lung Disease
Background/Purpose: Interstitial lung disease (ILD) causes significant complications and mortality in patients with rheumatoid arthritis (RA). We have previously shown that patients with RA-ILD had…Abstract Number: 1775 • ACR Convergence 2023
The Peptidyl Arginine Deiminase Inhibitor BB-CLA Decreases the Inflammatory and Fibrotic Responses in Macrophages and Rheumatoid Arthritis Synovial Fibroblasts Exposed to Fibrinogen Modified with Malondialdehyde-Acetaldehyde Adduct and Citrulline
Background/Purpose: Peptide citrullination and adduction with malondialdehyde-acetaldehyde adduct (MAA) are post-translational modifications involved in the pathogenesis of rheumatoid arthritis (RA). Anti-cyclic-citrullinated peptide antibodies are >90%…Abstract Number: 1681 • ACR Convergence 2022
Supernatants from Activated Macrophages Contain Citrullinated Vimentin and Induce Extracellular Matrix Deposition from Fibroblasts
Background/Purpose: Studies have shown that activated macrophages secrete several factors that promote human fibroblast-like synoviocyte (HFLS) activation, resulting in an invasive phenotype, that contributes to…Abstract Number: 1682 • ACR Convergence 2022
Peptidyl Arginine Deiminase Expression and Macrophage Polarization Following Stimulation with Citrullinated and Malondialdehyde-acetaldehyde Modified Fibrinogen
Background/Purpose: Post-translational modifications (PTM) of extracellular matrix proteins, such as fibrinogen, have been implicated in the pathogenesis of rheumatoid arthritis (RA). Citrullination, a type of…Abstract Number: 1683 • ACR Convergence 2022
Malondialdehyde-Acetaldehyde (MAA) Modified Matrix Gla Protein (MGP) Increases Citrullination by Human Macrophages
Background/Purpose: Malondialdehyde and acetaldehyde, by-products of lipid peroxidation, react with free amino groups on proteins to form a stable post-translational modification (PTM), termed MAA. MAA…Abstract Number: 1684 • ACR Convergence 2022
A Potent Inhibitor of PAD4 Suppresses Histone Citrullination in Vitro and in Vivo
Background/Purpose: Peptidyl arginine deaminase 4 (PAD4) catalyzes the conversion of arginine residues to citrulline, a post-translational modification that has been implicated in the auto-immune response…Abstract Number: 1735 • ACR Convergence 2022
Clonally Expanded Cytotoxic CD8+ T Cells Recognize Citrullinated Antigens in ACPA+ Rheumatoid Arthritis
Background/Purpose: Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with MHC polymorphisms. The shared epitope polymorphism in MHC class II genes is by far…Abstract Number: 0609 • ACR Convergence 2022
Macrophage Response to MAA Modified Fibrinogen in the Presence of Peptidyl Arginine Deiminase Inhibitor
Background/Purpose: The formation of citrullinated (CIT) proteins is catalyzed by a calcium-dependent peptidyl arginine deiminase (PAD). In rheumatoid arthritis (RA), synovial macrophages are main contributors…
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