Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Rheumatoid arthritis (RA) is associated with HLA-DRB1 alleles expressing the "shared epitope." RA is usually preceded by the emergence of anti-citrullinated protein autoantibodies (ACPAs). ACPAs recognize citrulline residues on numerous proteins. Conversion of arginine into citrulline is performed by enzymes called peptidyl arginine deiminases (PADs). We have previously demonstrated that C3H mice immunized with PADs can produce ACPAs by a hapten-carrier mechanism. Here, we address the influence of HLA-DR alleles in this model in mice expressing RA-associated HLA-DRB1*04:01 (KO/KI*04:01), HLA-DRB1*04:04 (KO/KI*04:04), or non-RA-associated HLA-DRB1*04:02 (KO/KI*04:02) after murine PAD2 immunization. Immunization with mPAD2 triggers production of ACPAs in wild-type (WT) and HLA-DR4 C57BL/6 mice. Both I-A and HLA-DR are involved in the activation of mPAD2-specific T lymphocytes. Among HLA-DR4 mice, mice expressing RA-associated HLA-DRB1*04:01 are the best responders to mPAD2 and the best anti-citrullinated peptide antibody producers.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545684 | PMC |
| http://dx.doi.org/10.1002/eji.202249889 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Glutathione Promotes Susceptibility to by Modulating Thiol Homeostasis in Arabidopsis.
Phytopathology
August 2025
University of California Davis Department of Entomology & Nematology, One Shields Avenue, Storer Hall 4208, Davis, Davis, California, United States, 95616;
Glutathione () is a key molecule that regulates numerous plant processes under both biotic and abiotic stress conditions. However, its role in plant responses to soil-borne pathogens, particularly the economically important root-knot nematodes (RKN; spp.), remains largely unexplored.
View Article and Find Full Text PDFA citrullinated histone H3 monoclonal antibody for immune modulation in sepsis.
Nat Commun
August 2025
Division of Surgical Sciences, Department of Surgery, University of Virginia, Charlottesville, VA, USA.
Citrullinated histone H3 (CitH3), released from immune cells during early sepsis, drives a vicious cycle of inflammation through excessive NETosis and pyroptosis, causing immune dysfunction and tissue damage. To regulate this process, we develop a humanized CitH3 monoclonal antibody (hCitH3-mAb) with high affinity and specificity to target this process. In murine models, hCitH3-mAb reduces cytokine production, mortality and acute lung injury (ALI) caused by LPS and Pseudomonas aeruginosa while enhancing bacteria phagocytosis in the lungs, spleen, and liver.
View Article and Find Full Text PDFPAD2-mediated citrullination of STAT3 enhances immunosuppressive function of PMN-MDSCs in tumor-bearing hosts.
Int Immunopharmacol
August 2025
Department of Laboratory Medicine, Jiangsu Province Engineering Research Center for Precise Diagnosis and Treatment of Inflammatory Diseases, Affiliated Hospital, Jiangsu University, Zhenjiang, China; Department of Immunology, Jiangsu Key Laboratory for Laboratory Medicine, Jiangsu University School
Myeloid-derived suppressor cells (MDSCs) play a key role in inhibiting antitumor immunity and helping tumor cells escape from the immune system. Citrullination is a unique posttranslational modification of proteins that has been found to play a role in tumorigenesis and development. We aimed to determine the role of citrullination regulating MDSCs function in tumor bearing hosts.
View Article and Find Full Text PDFCitH3, a Druggable Biomarker for Human Diseases Associated with Acute NETosis and Chronic Immune Dysfunction.
Pharmaceutics
June 2025
Division of Surgical Sciences, Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA.
Neutrophils are essential components of innate immunity, executing a range of effector functions including phagocytosis, degranulation, and the release of neutrophil extracellular traps (NETs). A key hallmark of NET formation is the presence of citrullinated histone H3 (CitH3), produced by peptidylarginine deiminases (PAD2 and PAD4) to facilitate chromatin decondensation. While NETs play critical antimicrobial roles, excessive or dysregulated NET formation, termed NETosis, can drive tissue injury, chronic inflammation, and organ dysfunction across a wide spectrum of diseases.
View Article and Find Full Text PDFPlacental Protein Citrullination Signatures Are Modified in Early- and Late-Onset Fetal Growth Restriction.
Int J Mol Sci
April 2025
Department of Neonatology, EGA Institute for Women's Health, University College London, London WC1E 6BT, UK.
Fetal growth restriction (FGR) is an obstetric condition most frequently caused by placental dysfunction. It is a major cause of perinatal morbidity with limited treatment options, so identifying the underpinning mechanisms is important. Peptidylarginine deiminases (PADs) are calcium-activated enzymes that mediate post-translational citrullination (deimination) of proteins, through conversion of arginine to citrulline.
View Article and Find Full Text PDF