Dataset Information

Citrullinated proteins in platelets and platelets releasing microparticles may serve as a potential target of ACPA

ABSTRACT: To investigate the expression of peptidylarginine deiminase (PAD) enzymes and mining citrullination proteins in human platelets and platelets releasing microparticles (PRMs), and to determine whether these less-studied platelets associated citrullination proteins can be targeted by anti-citrullinated protein antibodies (ACPA) in RA.

ORGANISM(S): Homo Sapiens

SUBMITTER: Hui Geng

PROVIDER: PXD037743 | iProX | Wed Oct 26 00:00:00 BST 2022

REPOSITORIES: iProX

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Publications

Platelets derived citrullinated proteins and microparticles are potential autoantibodies ACPA targets in RA patients.

Xu Minjie M Du Rong R Xing Wenping W Chen Xueting X Wan Jian J Wang Shengqing S Xiong Li L Nandakumar Kutty Selva KS Holmdahl Rikard R Geng Hui H

Frontiers in immunology 20230124

Citrullinated neoepitopes have emerged as key triggers of autoantibodies anti-citrullinated protein antibodies (ACPA) synthesis in rheumatoid arthritis (RA) patients. Apart from their critical role in homeostasis and thrombosis, platelets have a significant contribution to inflammation as well. Although anuclear in nature, platelets have an intricate post-translational modification machinery. Till now, citrullination in platelets and its contribution to trigger autoantibodies ACPA production in ...[more]

PMID: 36761728

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Project description:In sickle cell disease, ischemia-reperfusion injury and intravascular hemolysis produce endothelial dysfunction and vasculopathy characterized by reduced nitric oxide (NO) and arginine bioavailability. Recent functional studies of platelets in patients with sickle cell disease reveal a basally activated state, suggesting that pathological platelet activation may contribute to sickle cell disease vasculopathy. Studies were therefore undertaken to examine transcriptional signaling pathways in platelets that may be dysregulated in sickle cell disease. We demonstrate and validate here the feasibility of comparative platelet transcriptome studies on clinical samples from single donors, by the application of RNA amplification followed by microarray-based analysis of 54,000 probe sets. Data mining an existing microarray database, we identified 220 highly abundant genes in platelets and a subset of 72 relatively platelet-specific genes, defined by more than 10-fold increased expression compared to the median of other cell types in the database with amplified transcripts. The highly abundant platelet transcripts found in the current study included 82% or 70% of platelet abundant genes identified in two previous gene expression studies on non-amplified mRNA from pooled or apheresis samples, respectively. On comparing the platelet gene expression profiles in 18 patients with sickle cell disease in steady state to 12 African American controls, at a 3-fold cut-off and 5% false discovery rate, we identified ~100 differentially expressed genes, including multiple genes involved in arginine metabolism and redox homeostasis. Further characterization of these pathways using real time PCR and biochemical assays revealed increased arginase II expression and activity and decreased platelet polyamine levels. These studies suggest a potential pathogenic role for platelet arginase and altered arginine and polyamine metabolism in sickle cell disease and provide a novel framework for the study of disease-specific platelet biology. Keywords: Platelets, genes, enzymes, metabolism, signal transduction, sickle cell disease

Dataset Information

Citrullinated proteins in platelets and platelets releasing microparticles may serve as a potential target of ACPA

Publications

Platelets derived citrullinated proteins and microparticles are potential autoantibodies ACPA targets in RA patients.

Similar Datasets

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