keyword
https://read.qxmd.com/read/38524554/association-of-padi2-and-padi4-polymorphisms-in-covid-19-host-severity-and-non-survival
#1
JOURNAL ARTICLE
Ilse Adriana Gutiérrez-Pérez, Ivette Buendía-Roldán, Oscar Zaragoza-García, Gloria Pérez-Rubio, José Rafael Villafan-Bernal, Leslie Chávez-Galán, Isela Parra-Rojas, Rafael de Jesús Hernández-Zenteno, Ingrid Fricke-Galindo, Natividad Castro-Alarcón, Brandon Bautista-Becerril, Ramcés Falfán-Valencia, Iris Paola Guzmán-Guzmán
BACKGROUND: Enzymes of the peptidylarginine deiminase family (PADs) play a relevant role in the pathogenesis of COVID-19. However, the association of single nucleotide polymorphisms (SNPs) in their genes with COVID-19 severity and death is unknown. METHODOLOGY: We included 1045 patients who were diagnosed with COVID-19 between October 2020 and December 2021. All subjects were genotyped for PADI2 (rs1005753 and rs2235926) and PADI4 (rs11203366, rs11203367, and rs874881) SNPs by TaqMan assays and their associations with disease severity, death, and inflammatory biomarkers were evaluated...
March 30, 2024: Heliyon
https://read.qxmd.com/read/37759458/molecular-factors-in-pad2-padi2-and-pad4-padi4-are-associated-with-interstitial-lung-disease-susceptibility-in-rheumatoid-arthritis-patients
#2
JOURNAL ARTICLE
Karol J Nava-Quiroz, Jorge Rojas-Serrano, Gloria Pérez-Rubio, Ivette Buendia-Roldan, Mayra Mejía, Juan Carlos Fernández-López, Pedro Rodríguez-Henríquez, Noé Ayala-Alcantar, Espiridión Ramos-Martínez, Luis Alberto López-Flores, Alma D Del Ángel-Pablo, Ramcés Falfán-Valencia
Around 50% of rheumatoid arthritis (RA) patients show some extra-articular manifestation, with the lung a usually affected organ; in addition, the presence of anti-citrullinated protein antibodies (ACPA) is a common feature, which is caused by protein citrullination modifications, catalyzed by the peptidyl arginine deiminases (PAD) enzymes. We aimed to identify single nucleotide variants (SNV) in PADI2 and PADI4 genes (PAD2 and PAD4 proteins, respectively) associated with susceptibility to interstitial lung disease (ILD) in RA patients and the PAD2 and PAD4 levels...
September 8, 2023: Cells
https://read.qxmd.com/read/36224627/delayed-puberty-gonadotropin-abnormalities-and-subfertility-in-male-padi2-padi4-double-knockout-mice
#3
JOURNAL ARTICLE
Kelly L Sams, Chinatsu Mukai, Brooke A Marks, Chitvan Mittal, Elena Alina Demeter, Sophie Nelissen, Jennifer K Grenier, Ann E Tate, Faraz Ahmed, Scott A Coonrod
BACKGROUND: Peptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo. METHODS: Preliminary analysis of Padi2 and Padi4 single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation...
October 12, 2022: Reproductive Biology and Endocrinology: RB&E
https://read.qxmd.com/read/35979360/genetic-basis-of-defects-in-immune-tolerance-underlying-the-development-of-autoimmunity
#4
REVIEW
Anne M Hocking, Jane H Buckner
Genetic variants associated with susceptibility to autoimmune disease have provided important insight into the mechanisms responsible for the loss of immune tolerance and the subsequent development of autoantibodies, tissue damage, and onset of clinical disease. Here, we review how genetic variants shared across multiple autoimmune diseases have contributed to our understanding of global tolerance failure, focusing on variants in the human leukocyte antigen region, PTPN2 and PTPN22, and their role in antigen presentation and T and B cell homeostasis...
2022: Frontiers in Immunology
https://read.qxmd.com/read/34881329/suppression-of-epithelial-abnormalities-by-nintedanib-in-induced-rheumatoid-arthritis-associated-interstitial-lung-disease-mouse-model
#5
JOURNAL ARTICLE
Yoko Miura, Hirotsugu Ohkubo, Akio Niimi, Satoshi Kanazawa
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is relevant for the prognosis in patients with RA. Nintedanib, which inhibits both receptor and non-receptor type tyrosine kinases, is an antifibrotic drug for the treatment of progressive fibrosing ILDs, such as idiopathic pulmonary fibrosis and systemic sclerosis-associated interstitial lung disease. Little is known about the effects of nintedanib on RA-ILD. We examined the characteristics of a novel induced RA-ILD (iRA-ILD) mouse model and the effects of nintedanib on the model...
October 2021: ERJ Open Research
https://read.qxmd.com/read/34733271/-padi4-polymorphisms-confer-risk-of-anti-ccp-positive-rheumatoid-arthritis-in-synergy-with-hla-drb1-04-and-smoking
#6
JOURNAL ARTICLE
Laura Massarenti, Christian Enevold, Dres Damgaard, Niels Ødum, Peter Garred, Morten Frisch, Miriam A Shelef, Søren Jacobsen, Claus Henrik Nielsen
Peptidylarginine deiminases (PADs) catalyze citrullination, a post-translational modification playing a pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA). The interplay between single nucleotide polymorphisms (SNPs) in the PADI genes and known risk factors for ACPA-positive RA, including smoking, HLA-DR4 and -1, and the PTPN22 R620W polymorphism, was investigated. We typed four PADI2 SNPs, four PADI4 SNPs, and the PTPN22 R620W SNP in 445 Danish RA patients and 533 age-matched healthy controls, as well as in 200 North American RA patients and 100 age- and sex-matched controls...
2021: Frontiers in Immunology
https://read.qxmd.com/read/34569542/the-clinical-and-prognostic-significance-of-protein-arginine-deiminases-2-and-4-in-colorectal-cancer
#7
JOURNAL ARTICLE
Mohamed Gijon, Rachael L Metheringham, Michael S Toss, Samantha J Paston, Lindy G Durrant
INTRODUCTION: Protein arginine deiminases (PADIs) are a family of enzymes that catalyse the post-translational modification of proteins. Association between PADI expression and clinicopathology, protein expression, and outcome was determined. METHODS: PADI2 and PADI4 expression was assessed immunohistochemically in a cohort of colorectal cancer (CRC) patients. RESULTS: CRC tissues expressed variable levels of PADI2 which was mainly localised in the cytoplasm and correlated with patient survival (p = 0...
September 16, 2021: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://read.qxmd.com/read/34561224/cd8-t-cells-variably-recognize-native-versus-citrullinated-grp78-epitopes-in-type-1-diabetes
#8
JOURNAL ARTICLE
Marie Eliane Azoury, Fatoumata Samassa, Mijke Buitinga, Laura Nigi, Noemi Brusco, Aïsha Callebaut, Matthieu Giraud, Magali Irla, Ana Ines Lalanne, Alexia Carré, Georgia Afonso, Zhicheng Zhou, Barbara Brandao, Maikel L Colli, Guido Sebastiani, Francesco Dotta, Maki Nakayama, Decio L Eizirik, Sylvaine You, Sheena Pinto, Mark J Mamula, Yann Verdier, Joelle Vinh, Soren Buus, Chantal Mathieu, Lut Overbergh, Roberto Mallone
In type 1 diabetes, autoimmune β-cell destruction may be favored by neoantigens harboring posttranslational modifications (PTMs) such as citrullination. We studied the recognition of native and citrullinated glucose-regulated protein (GRP)78 peptides by CD8+ T cells. Citrullination modulated T-cell recognition and, to a lesser extent, HLA-A2 binding. GRP78-reactive CD8+ T cells circulated at similar frequencies in healthy donors and donors with type 1 diabetes and preferentially recognized either native or citrullinated versions, without cross-reactivity...
December 2021: Diabetes
https://read.qxmd.com/read/34073629/the-expression-of-non-coding-rnas-and-their-target-molecules-in-rheumatoid-arthritis-a-molecular-basis-for-rheumatoid-pathogenesis-and-its-potential-clinical-applications
#9
REVIEW
Chang-Youh Tsai, Song-Chou Hsieh, Chih-Wei Liu, Cheng-Hsun Lu, Hsien-Tzung Liao, Ming-Han Chen, Ko-Jen Li, Cheng-Han Wu, Cheih-Yu Shen, Yu-Min Kuo, Chia-Li Yu
Rheumatoid arthritis (RA) is a typical autoimmune-mediated rheumatic disease presenting as a chronic synovitis in the joint. The chronic synovial inflammation is characterized by hyper-vascularity and extravasation of various immune-related cells to form lymphoid aggregates where an intimate cross-talk among innate and adaptive immune cells takes place. These interactions facilitate production of abundant proinflammatory cytokines, chemokines and growth factors for the proliferation/maturation/differentiation of B lymphocytes to become plasma cells...
May 26, 2021: International Journal of Molecular Sciences
https://read.qxmd.com/read/32785008/the-essential-role-of-peptidylarginine-deiminases-2-for-cytokines-secretion-apoptosis-and-cell-adhesion-in-macrophage
#10
JOURNAL ARTICLE
Hui-Chun Yu, Chien-Hsueh Tung, Kuang-Yung Huang, Hsien-Bin Huang, Ming-Chi Lu
OBJECTIVE: The study aims to investigate the functional roles of peptidylarginine deiminase 2 (PADI2) in macrophages. METHODS: The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (Cas9) system was used to knockout PADI2 in U937 cells. U937 cells were introduced to differentiate macrophages and were stimulated with lipopolysaccharides (LPS). The protein expression of PADI2, PADI4, and citrullinated proteins were analyzed by Western blotting...
August 10, 2020: International Journal of Molecular Sciences
https://read.qxmd.com/read/32629995/putative-roles-for-peptidylarginine-deiminases-in-covid-19
#11
JOURNAL ARTICLE
Elif Damla Arisan, Pinar Uysal-Onganer, Sigrun Lange
Peptidylarginine deiminases (PADs) are a family of calcium-regulated enzymes that are phylogenetically conserved and cause post-translational deimination/citrullination, contributing to protein moonlighting in health and disease. PADs are implicated in a range of inflammatory and autoimmune conditions, in the regulation of extracellular vesicle (EV) release, and their roles in infection and immunomodulation are known to some extent, including in viral infections. In the current study we describe putative roles for PADs in COVID-19, based on in silico analysis of BioProject transcriptome data (PRJNA615032 BioProject), including lung biopsies from healthy volunteers and SARS-CoV-2-infected patients, as well as SARS-CoV-2-infected, and mock human bronchial epithelial NHBE and adenocarcinoma alveolar basal epithelial A549 cell lines...
June 30, 2020: International Journal of Molecular Sciences
https://read.qxmd.com/read/31058095/a-novel-citrullinated-modification-of-histone-3-and-its-regulatory-mechanisms-related-to-ipo-38-antibody-labeled-protein
#12
JOURNAL ARTICLE
Shuzheng Song, Zhen Xiang, Jun Li, Jun Ji, Ranlin Yan, Zhenggang Zhu, Yingyan Yu
IPO-38 is a potential biomarker for early diagnosis of gastric cancer that we recently identified. Although we characterized its chemical nature as a nucleosome histone, we suspected the existence of histone modification for the IPO-38 antibody-labeled protein. Here, we used a commercially available modified histone peptide array to identify the type and site of histone modification labeled by the IPO-38 monoclonal antibody. In protein array analysis, the citrulline modification of histone 3 on arginine 26 (H3R26Cit) yielded the strongest signal...
2019: Frontiers in Oncology
https://read.qxmd.com/read/31039829/increased-peptidylarginine-deiminases-expression-during-the-macrophage-differentiation-and-participated-inflammatory-responses
#13
JOURNAL ARTICLE
Ning-Sheng Lai, Hui-Chun Yu, Chien-Hsueh Tung, Kuang-Yung Huang, Hsien-Bin Huang, Ming-Chi Lu
OBJECTIVE: To investigate the expression of peptidylarginine deiminases (PADIs) during macrophage differentiation and its role in inflammatory responses. METHODS: The protein expression of PADI2, PADI4, and citrullinated histone 3 in U937 cells, differentiated macrophages, and macrophages stimulated with lipopolysaccharides (LPS) were analyzed by Western blotting. Three PADI inhibitors were used for assessing their effects on the secretion of proinflammatory cytokines in macrophages...
April 30, 2019: Arthritis Research & Therapy
https://read.qxmd.com/read/30064459/increased-citrullination-and-expression-of-peptidylarginine-deiminases-independently-of-p-gingivalis-and-a-actinomycetemcomitans-in-gingival-tissue-of-patients-with-periodontitis
#14
JOURNAL ARTICLE
Marianne Engström, Kaja Eriksson, Linkiat Lee, Monika Hermansson, Anders Johansson, Anthony P Nicholas, Natalija Gerasimcik, Karin Lundberg, Lars Klareskog, Anca Irinel Catrina, Tülay Yucel-Lindberg
BACKGROUND: A relationship between rheumatoid arthritis (RA) and periodontitis has been suggested from findings that individuals with RA are prone to have advanced periodontitis and vice versa. In search of possible common pathogenetic features of these two diseases, we investigated the presence of citrullinated proteins and expression of endogenous peptidylarginine deiminases (PAD2 and PAD4), in periodontal tissue of individuals with periodontitis and healthy controls, in relation to the periodontal pathogens Porphyromonas gingivalis (P...
July 31, 2018: Journal of Translational Medicine
https://read.qxmd.com/read/29287593/upregulation-of-citrullination-pathway-from-autoimmune-to-idiopathic-lung-fibrosis
#15
JOURNAL ARTICLE
Katerina D Samara, Athina Trachalaki, Eliza Tsitoura, Anastasios V Koutsopoulos, Eleni D Lagoudaki, Ismini Lasithiotaki, George Margaritopoulos, Panagiotis Pantelidis, Eleni Bibaki, Nikolaos M Siafakas, Nikolaos Tzanakis, Athol U Wells, Katerina M Antoniou
BACKGROUND: Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity. Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis remains unclear...
December 29, 2017: Respiratory Research
https://read.qxmd.com/read/29148420/the-expression-of-mrna-for-peptidylarginine-deiminase-type-2-and-type-4-in-bone-marrow-cd34-cells-in-rheumatoid-arthritis
#16
JOURNAL ARTICLE
Tatsuo Nagai, Yu Matsueda, Tetsuya Tomita, Hideki Yoshikawa, Shunsei Hirohata
OBJECTIVES: Antibodies directed to citrullinated proteins are highly specific for rheumatoid arthritis (RA). Citrullination is catalyzed by peptidylarginine deiminase (PAD) enzymes. The current study examined the mRNA expression of PADI2 and PADI4 in bone marrow (BM) CD34+ cells from RA patients. METHODS: CD34+ cells were purified from BM samples obtained from 48 RA patients and from 30 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest...
March 2018: Clinical and Experimental Rheumatology
https://read.qxmd.com/read/27150598/decreased-severity-of-experimental-autoimmune-arthritis-in-peptidylarginine-deiminase-type-4-knockout-mice
#17
JOURNAL ARTICLE
Akari Suzuki, Yuta Kochi, Hirofumi Shoda, Yu Seri, Keishi Fujio, Tetsuji Sawada, Ryo Yamada, Kazuhiko Yamamoto
BACKGROUND: Peptidylarginine deiminase type 4 (PADI4) has been identified as a susceptibility gene for rheumatoid arthritis (RA) by genome-wide association studies. PADI4 is highly expressed in the bone marrow, macrophages, neutrophils, and monocytes. Peptidyl citrulline is an interesting molecule in RA because it is a target antigen for anti-citrullinated peptide antibodies, and only PADs (translated proteins from PADI genes) can provide peptidyl citrulline via the modification of protein substrates...
May 5, 2016: BMC Musculoskeletal Disorders
https://read.qxmd.com/read/27060082/identification-of-citrullinated-peptides-in-the-synovial-fluid-of-patients-with-rheumatoid-arthritis-using-lc-maldi-tof-tof
#18
JOURNAL ARTICLE
Fei Wang, Fang-Fang Chen, Wen-Bo Gao, Hai-Yong Wang, Ning-Wei Zhao, Min Xu, De-Yu Gao, Wei Yu, Xiao-Ling Yan, Jian-Ning Zhao, Xiao-Jun Li
The objective of the study is to investigate potential citrullinated autoantigens as targets of anti-citrullinated protein antibodies (ACPAs) response in synovial fluids (SFs) of patients with rheumatoid arthritis (RA). SFs from six RA patients and six osteoarthritis (OA) patients as controls were collected. The citrullinated proteins in SFs were extracted by immunoprecipitation with rabbit anti-citrulline antibodies. Matrix-assisted laser desorption/ionization time of flight mass spectrometry/time of flight mass spectrometry (MALDI-TOF/TOF) mass spectrometry was subsequently performed to discover a characteristic neutral loss to finally determine citrullinated autoantigens...
September 2016: Clinical Rheumatology
https://read.qxmd.com/read/26255191/the-amount-of-citrullinated-proteins-in-synovial-tissue-is-related-to-serum-anti-cyclic-citrullinated-peptide-anti-ccp-antibody-levels
#19
JOURNAL ARTICLE
Elizabeth Olivares-Martínez, Diego F Hernández-Ramírez, Carlos A Núñez-Álvarez, Antonio R Cabral, Luis Llorente
The objective of this study was to determine the relationship between citrullinated proteins in synovial tissue with peripheral anti-citrullinated peptides autoantibodies (ACPA) and peptidylarginine deiminase (PADI) PADI2, PADI3, and PADI4 messenger RNA (mRNA) expressions in synovial tissue and fibroblast-like synoviocytes in rheumatoid arthritis (RA) patients. Eleven RA and 12 osteoarthritis (OA) patients who underwent knee replacement surgery were studied. We detected citrullinated proteins in synovial tissue homogenates by western blot and serum ACPA by ELISA to anti-cyclic citrullinated peptide (anti-CCP) antibodies, and PADI2, PADI3, and PADI4 mRNA expressions in synovial tissue and in fibroblast-like synoviocytes...
January 2016: Clinical Rheumatology
https://read.qxmd.com/read/24339914/padi2-is-significantly-associated-with-rheumatoid-arthritis
#20
JOURNAL ARTICLE
Xiaotian Chang, Yifang Xia, Jihong Pan, Qingsong Meng, Yan Zhao, Xinfeng Yan
Citrullination, a posttranslational modification of peptidyl arginine to citrulline, plays an essential role in rheumatoid arthritis (RA). Citrullination is catalyzed by a group of peptidylarginine deiminases (PADs) including PADI 1, 2, 3, 4 and 6. Many studies have indicated that the gene encoding PADI4 is a factor in susceptibility to RA. Some studies have detected PADI2 expression in RA synovial tissues, suggesting that PADI2 also plays an important role in the disease. This study evaluated the possible association between the PADI2-encoding gene and RA...
2013: PloS One
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