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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
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...
November 14, 2017: Clinical and Experimental Rheumatology
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
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
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
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
Chun Lai Too, Shahnaz Murad, Jasbir Singh Dhaliwal, Per Larsson, Xia Jiang, Bo Ding, Lars Alfredsson, Lars Klareskog, Leonid Padyukov
INTRODUCTION: The majority of our knowledge regarding disease-related mechanisms of uncontrolled citrullination and anti-citrullinated protein antibody development in rheumatoid arthritis (RA) was investigated in Caucasian populations. However, peptidylarginine deiminase (PADI) type 4 gene polymorphisms are associated with RA in East Asian populations and weak or no association was found in Caucasian populations. This study explores the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal of elucidating generalizability of association in non-Caucasian populations...
2012: Arthritis Research & Therapy
Young Ho Lee, Sang-Cheol Bae, Sung Jae Choi, Jong Dae Ji, Gwan Gyu Song
The aim of this study was to explore candidate single nucleotide polymorphisms (SNPs) and candidate mechanisms of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Two SLE genome-wide association studies (GWASs) datasets were included in this study. Meta-analysis was conducted using 737,984 SNPs in 1,527 SLE cases and 3,421 controls of European ancestry, and 4,429 SNPs that met a threshold of p < 0.01 in a Korean RA GWAS dataset was used. ICSNPathway (identify candidate causal SNPs and pathways) analysis was applied to the meta-analysis results of the SLE GWAS datasets, and a RA GWAS dataset...
December 2012: Molecular Biology Reports
Sylvie Ferrari-Lacraz, Mireille Sebbag, Rachel Chicheportiche, Céline Foulquier, Guy Serre, Jean-Michel Dayer
OBJECTIVE: The antigenic targets of the rheumatoid arthritis (RA)-associated autoantibodies to "citrullinated" proteins are generated following citrullination by a peptidylarginine deiminase (PAD). Of the five PAD isotypes, two - PAD2 and PAD4 - are expressed in RA synovial tissue. Within this tissue, the activation of macrophages and fibroblasts mediated by T-cell contact or driven by cytokines plays a prominent part in the pathogenesis. We wanted to determine whether cytokine stimulation and contact with T cells could play a role in PAD expression by peripheral blood monocytes and fibroblastic synoviocytes...
June 2012: European Cytokine Network
Ola Kilsgård, Pia Andersson, Martin Malmsten, Sara L Nordin, Helena M Linge, Mette Eliasson, Eva Sörenson, Jonas S Erjefält, Johan Bylund, Anders I Olin, Ole E Sørensen, Arne Egesten
Bacterial colonization of the lower respiratory tract is frequently seen in chronic obstructive pulmonary disease (COPD), and may cause exacerbations leading to disease progression. Antimicrobial peptides comprise an important part of innate lung immunity, and not least the cathelicidin human cationic antimicrobial protein-18/LL-37. Peptidylarginine deiminases (PADIs) post-translationally modify proteins by converting cationic peptidylarginine residues to neutral peptidylcitrulline. An increased presence of PADI2 and citrullinated proteins was demonstrated in the lungs of smokers...
February 2012: American Journal of Respiratory Cell and Molecular Biology
Alyssa K Johnsen, William Valdar, Louis Golden, Adriana Ortiz-Lopez, Robert Hitzemann, Jonathan Flint, Diane Mathis, Christophe Benoist
OBJECTIVE: Susceptibility to inflammatory arthritis is determined by a complex set of environmental and genetic factors, but only a portion of the genetic effect can be explained. Conventional genome-wide screens of arthritis models using crosses between inbred mice have been hampered by the low resolution of results and by the restricted range of natural genetic variation sampled. The aim of this study was to address these limitations by performing a genome-wide screen for determinants of arthritis severity using a genetically heterogeneous cohort of mice...
September 2011: Arthritis and Rheumatism
Makiko Nakayama-Hamada, Akari Suzuki, Kazuishi Kubota, Tomoko Takazawa, Mizuko Ohsaka, Reimi Kawaida, Mitsuru Ono, Atsushi Kasuya, Hidehiko Furukawa, Ryo Yamada, Kazuhiko Yamamoto
In the sera of rheumatoid arthritis (RA) patients, autoantibodies directed to citrullinated proteins are found with high specificity for RA. Peptidylarginine deiminases (PADIs) are enzymes responsible for protein citrullination. Among many isoforms of PADIs, only PADI4 has been identified as an RA-susceptibility gene. To understand the mechanisms of the initiation and progression of RA, we compared the properties of two PADIs, human PADI2 and human PADI4, which are present in the synovial tissues of RA patients...
February 4, 2005: Biochemical and Biophysical Research Communications
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