Abstracts tagged "citrullination"

Abstract Number: 0045 • ACR Convergence 2024
Proteomic Analysis of the Rheumatoid Arthritis Citrullinome Reveals an Enrichment of Citrullinated Complement Proteins
Khushali Trivedi¹, Clarissa Klenke², Jun Kim¹, Jeba Atkia Maisha², Alina Sememenko¹, XIAOBO MENG², Mario Navarrete¹, Hani El-Gabalawy² and Liam O'Neil², ¹University of Manitoba, Winnipeg, Canada, ²University of Manitoba, Winnipeg, MB, Canada
Background/Purpose: Citrullination is a key physiological process that drives autoantibody formation in Rheumatoid Arthritis (RA). This irreversible post-translational modification of the amino acid arginine is…
Abstract Number: 0046 • ACR Convergence 2024
Impaired Neutrophil Extracellular Trap (NET) Degradation in Rheumatoid Arthritis (RA) and Pre-clinical RA Is Mediated by Anti-NET Antibodies
Jeba Atkia Maisha¹, Alina Sememenko², Jun Kim², Mario Navarrete², XIAOBO MENG¹, Hani El-Gabalawy¹ and Liam O'Neil¹, ¹University of Manitoba, Winnipeg, MB, Canada, ²University of Manitoba, Winnipeg, Canada
Background/Purpose: Rheumatoid Arthritis (RA) begins after a prolonged preclinical phase which is marked by the development of RA antibodies, typically against citrullinated proteins (ACPA). The…
Abstract Number: 0062 • ACR Convergence 2024
Pro-Fibrotic Effects of Malondialdehyde-Acetaldehyde-Adducted and/or Citrullinated Proteins on Macrophages and Human Lung Fibroblasts
Lauren Klingemann¹, Nozima Aripova¹, Nigina Aripova², Michael Duryee¹, Carlos Hunter¹, Jill Poole¹, Bryant England¹, Ted Mikuls¹ and Geoffrey Thiele¹, ¹University of Nebraska Medical Center, Omaha, NE, ²WUSTL, St. Louis, MO
Background/Purpose: Clinically evident rheumatoid arthritis-associated interstitial lung disease (RA-ILD) affects approximately 10-15% of patients with rheumatoid arthritis (RA) and accounts for the most overrepresented cause…
Abstract Number: 0065 • ACR Convergence 2024
Evidence of Membranolytic Targeting and Intracellular Citrullinationin Neutrophils Isolated from Patients with Rheumatoid Arthritis
Neela Fatemeh Moadab¹, Tal Gazitt², Rayan Najjar¹, Ethan Le¹, J Lee Nelson³, Vijay Joshua⁴, Keith Elkon¹, Caroline Grönwall⁴ and Tomas Mustelin¹, ¹University of Washington, Seattle, WA, ²Carmel Hospital, Haifa, Israel, ³University of Washington and Fred Hutchinson Cancer Center, Seattle, WA, ⁴Karolinska Institutet, Stockholm, Sweden
Background/Purpose: Anti-citrullinated protein autoantibodies (ACPA) are diagnostic for rheumatoid arthritis (RA). The antigens recognized by these autoantibodies are produced by protein arginine deiminases (PADs), particularly…
Abstract Number: 1846 • ACR Convergence 2024
Citrullinated Vimentin-reactive Immune-regulatory CD4+CD39+TIGIThi T Cells Expand During Drug Free Remission in HLA-DR Shared-epitope+ ACPA+ Rheumatoid Arthritis
Amy Anderson¹, Henrique de Paula Lemos¹, Hendrik Nel², Sofia Sorbet Santiago¹, Fiona Rayner³, Abbie Degnan¹, Imogen Wilson¹, Julie Diboll¹, Jasmine Sim¹, Andrew Melville⁴, Stefan Siebert⁴, Iain McInnes⁵, Carl Goodyear⁴, Catharien Hilkens¹, Andrew Filer⁶, Karim Raza⁶, Christopher Buckley⁷, Hugh Reid⁸, Kenneth Baker¹, Arthur Pratt³, Jamie Rossjohn⁸, Ranjeny Thomas⁹ and John Isaacs¹, ¹Translational and Clinical Research Institute, NIHR Newcastle Biomedical Research Centre, Newcastle University and The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom, ²Frazer Institute, The University of Queensland, Translational Research Institute, Brisbane, Australia, ³Translational and Clinical Research Institute, NIHR Newcastle Biomedical Research Centre, Newcastle University and The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, England, United Kingdom, ⁴School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom, ⁵University of Glasgow, College of Medical Veterinary and Life Sciences, Glasgow, United Kingdom, ⁶Rheumatology Research Group, Institute for Inflammation and Ageing, NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Birmingham, United Kingdom, ⁷Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom, ⁸Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia, ⁹University of Queensland, Brisbane, Australia
Background/Purpose: There is a need for immunotherapy that sustains symptom remission without ongoing need for disease modifying drugs (DMARDs). In a phase 1b trial of…
Abstract Number: 1858 • ACR Convergence 2024
Co-modification of Citrullinated Proteins with Malondialdehyde-Acetaldehyde Leads to Amplified T Cell Responses and Increased Disease-specific Autoantibody Concentrations
Breanna Butler¹, Wenxian Zhou², Michael Duryee¹, Nozima Aripova¹, Engle Sharp¹, Carlos Hunter¹, Bridget Kramer¹, Harlan Sayles¹, James O'Dell¹, Geoffrey Thiele¹, Bryant England¹, Joshua Baker³, Andreas Reimold⁴, Gail Kerr⁵ and Ted Mikuls¹, ¹University of Nebraska Medical Center, Omaha, NE, ²University of Nebraska Medical Center, Bellevue, NE, ³University of Pennsylvania, Philadelphia, PA, ⁴Dallas VA Medical Center, Dallas, TX, ⁵Washington DC VAMC/Georgetown and Howard Universities, Washington, DC
Background/Purpose: Anti-citrullinated protein antibody (ACPA) is highly specific to rheumatoid arthritis (RA). Beyond citrullination, other post-translational protein modifications including malondialdehyde-acetaldehyde (MAA) are targeted by T…
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
Leonie Middelink¹, Renato Chirivi², Helmuth van Es², Eric Meldrum², Peter van Zandvoort², Tirza Bruurmijn², Matthijs Moerland³ and Patrick Round², ¹Middelinc., Utrecht, Netherlands, ²Citryll BV, Oss, Netherlands, ³CHDR, Leiden, Netherlands
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
Min Yang¹, song feng¹, yuling wen¹, Xiaoming ren¹, Huijuan Li¹, lili yao¹, Zhi xie² and Wenge zhong¹, ¹Regor Therapeutics, Shanghai, China, ²Regor Pharmaceuticals, Inc., San Francisco, CA
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
Maarten van der Linden¹, Sangeeta Kumari¹, Daphne Montizaan¹, Stephanie van Dalen¹, Annemarie Kip¹, Martyn FOSTER², Inge Reinieren¹, Elsa Neubert³, Luise Erpenbeck⁴, Tirza Bruurmijn¹, Peter van Zandvoort¹, Paul Vink¹, Eric Meldrum⁵, Helmuth van Es¹ and Renato Chirivi¹, ¹Citryll BV, Oss, Netherlands, ²Experimental Pathology Consultancy, Benfleet, United Kingdom, ³Leiden Academic Centre for Drug Research, Leiden, Netherlands, ⁴University Medical Center Münster, General Dermatology and Venereology, Münster, Germany, ⁵Citryll BV, Basel, Switzerland
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
Sara Charmsaz¹, Jeff Tracy¹, Elizabeth Whalen¹, John Bui¹, Anne-Renee van der Vuurst de Vries¹, Vivianne Malmström² and Michelle Blake¹, ¹Sonoma Biotherapeutics, Seattle, WA, ²Karolinska Institutet, Stockholm, Sweden
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
Sheri Saunders, Garth Blackler, Patti Kiser, Ewa Cairns and Lillian Barra, Western University, London, ON, Canada
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
Rachna Talluri¹, Sudeshna Sen², Timothy Wilson³, Adam Savage⁴, Mark Gillespie⁴, Tom Bumol⁴, Marie Feser¹, Jill Norri⁵, Michael Holer¹, kevin Deane¹, Paul Thompson² and Kristen Demoruelle¹, ¹University of Colorado Anschutz Medical Campus, Aurora, CO, ²University of Massachusetts Chan Medical School, Worcester, MA, ³Thomas Jefferson University, Philadelphia, PA, ⁴Allen Institute for Immunology, Seattle, WA, ⁵Colorado School of Public Health, Denver, CO
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
S Janna Bashar, Caitlyn Holmes and Miriam Shelef, University of Wisconsin, Madison, WI
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
Breanna Butler¹, Jill Poole¹, Michael Duryee¹, Nozima Aripova¹, Carlos Hunter¹, Bridget Kramer¹, James O'Dell¹, Geoffrey Thiele¹, Bryant England¹ and Ted R Mikuls², ¹University of Nebraska Medical Center, Omaha, NE, ²Division of Rheumatology and Immunology, University of Nebraska Medical Center, Omaha, NE
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
Jack Mordeson¹, Nozima Aripova¹, Michael Duryee¹, James O'Dell¹, Bryant England¹, Daniel Anderson¹, Ted R Mikuls² and Geoffrey Thiele¹, ¹University of Nebraska Medical Center, Omaha, NE, ²Division of Rheumatology and Immunology, University of Nebraska Medical Center, Omaha, NE
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%…

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