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https://www.readbyqxmd.com/read/28291534/ptpn22-1123g-c-polymorphism-and-anti-cyclic-citrullinated-protein-antibodies-in-rheumatoid-arthritis
#1
José Francisco Muñoz-Valle, Jorge Ramón Padilla-Gutiérrez, Jorge Hernández-Bello, Yeniley Ruiz-Noa, Yeminia Valle, Claudia Azucena Palafox-Sánchez, Isela Parra-Rojas, Sergio Ramón Gutiérrez-Ureña, Hector Rangel-Villalobos
BACKGROUND AND OBJECTIVES: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase -Lyp- and has been associated with different autoimmune disorders. The PTPN22 -1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 -1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico...
March 10, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28262800/the-influence-of-population-stratification-on-genetic-markers-associated-with-type-1-diabetes
#2
Karla Fabiana Brasil Gomes, Aritânia Sousa Santos, Cintia Semzezem, Márcia Regina Correia, Luciano Abreu Brito, Marcelo Ortega Ruiz, Rosa Tsuneshiro Fukui, Sergio Russo Matioli, Maria Rita Passos-Bueno, Maria Elizabeth Rossi da Silva
Ethnic admixtures may interfere with the definition of type 1 diabetes (T1D) risk determinants. The role of HLA, PTPN22, INS-VNTR, and CTLA4 in T1D predisposition was analyzed in Brazilian T1D patients (n = 915), with 81.7% self-reporting as white and 789 controls (65.6% white). The results were corrected for population stratification by genotyping 93 ancestry informative markers (AIMs) (BeadXpress platform). Ancestry composition and structural association were characterized using Structure 2.3 and STRAT...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28243041/rs2476601-polymorphism-in-ptpn22-is-associated-with-crohn-s-disease-but-not-with-ulcerative-colitis-a-meta-analysis-of-16-838-cases-and-13-356-controls
#3
Abdellah Hedjoudje, Chérifa Cheurfa, Clément Briquez, Allen Zhang, Stéphane Koch, Lucine Vuitton
BACKGROUND: Although the rs2476601 polymorphism of PTPN22 has been reported to be a susceptibility gene for Crohn's disease (CD), results from different studies vary and remain inconclusive. Also, no association has been found between rs2476601 and the risk of ulcerative colitis (UC). The aim of this meta-analysis was to investigate the association between this PTPN22 polymorphism (rs2476601) and the risk of inflammatory bowel disease, UC and CD. METHODS: We performed a meta-analysis by identifying relevant candidate gene-based studies from EMBASE and MEDLINE...
2017: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
https://www.readbyqxmd.com/read/28237724/the-common-autoimmunity-predisposing-620arg%C3%A2-%C3%A2-trp-variant-of-ptpn22-modulates-macrophage-function-and-morphology
#4
Meihang Li, Hugues Beauchemin, Natalija Popovic, Alan Peterson, Eva d'Hennezel, Ciriaco A Piccirillo, Chao Sun, Constantin Polychronakos
The C1858T single nucleotide polymorphism (SNP) in PTPN22 (protein tyrosine phosphatase nonreceptor 22) leads to the 620 Arg to Trp polymorphism in its encoded human protein LYP. This allelic variant is associated with multiple autoimmune diseases, including type 1 diabetes (T1D), Crohn's disease, rheumatoid arthritis and systemic lupus erythematosus. However, the underlying mechanisms are poorly understood. To study how this polymorphism influences the immune system, we generated a mouse strain with a knock-in of the Trp allele, imitating the human disease-associated variant...
February 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28210620/association-of-ptpn22-haplotypes-1123g-c-1858c-t-with-rheumatoid-arthritis-in-western-mexican-population
#5
Yeniley Ruiz-Noa, Jorge Ramón Padilla-Gutiérrez, Jorge Hernández-Bello, Claudia Azucena Palafox-Sánchez, Yeminia Valle, Edith Oregón-Romero, Ana Laura Pereira-Suárez, Ana Guilaisne Bernard-Medina, José Francisco Muñoz-Valle
Rheumatoid arthritis (RA) is an autoimmune disease characterized by the presence of antibodies against cyclic citrullinated peptide (anti-CCP), a consequence of the breakdown of immune tolerance. The lymphoid tyrosine phosphatase (Lyp) protein has significant effects on maintenance of peripheral immune tolerance. Two polymorphic variants (-1123G>C and +1858C>T) at PTPN22 gene that encodes this protein have been associated with autoimmune disorders and found in strong linkage disequilibrium in Caucasian population...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/28029757/identification-of-functional-and-expression-polymorphisms-associated-with-risk-for-anti-neutrophil-cytoplasmic-autoantibody-associated-vasculitis
#6
Peter A Merkel, Gang Xie, Paul A Monach, Xuemei Ji, Dominic J Ciavatta, Jinyoung Byun, Benjamin D Pinder, Ai Zhao, Jinyi Zhang, Yohannes Tadesse, David Qian, Matthew Weirauch, Rajan Nair, Alex Tsoi, Christian Pagnoux, Simon Carette, Sharon Chung, David Cuthbertson, John C Davis, Paul F Dellaripa, Lindsy Forbess, Ora Gewurz-Singer, Gary S Hoffman, Nader Khalidi, Curry Koening, Carol A Langford, Alfred D Mahr, Carol McAlear, Larry Moreland, E Philip Seo, Ulrich Specks, Robert F Spiera, Antoine Sreih, E William St Clair, John H Stone, Steven R Ytterberg, James T Elder, Jia Qu, Toshiki Ochi, Naoto Hirano, Jeffrey C Edberg, Ronald J Falk, Christopher I Amos, Katherine A Siminovitch
OBJECTIVE: To identify risk alleles relevant to the cause and biology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We conducted a genome-wide association and subsequent replication study including 1986 cases of AAV [granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)] and 4723 controls. Meta-analysis of these datasets and functional annotation of identified risk loci were performed and candidate disease variants with unknown functional effects investigated for impact on gene expression and/or protein function...
December 28, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27936393/suppression-of-protein-tyrosine-phosphatase-ptpn22-gene-induces-apoptosis-in-t-cell-leukemia-cell-line-jurkat-through-the-akt-and-erk-pathways
#7
Elham Baghbani, Behzad Baradaran, Fatemeh Pak, Leila Mohammadnejad, Daryoush Shanehbandi, Behzad Mansoori, Vahid Khaze, Noushin Montazami, Ali Mohammadi, Parviz Kokhaei
The aim of this study was to investigate the effect of specific PTPN22 small interfering RNAs (siRNAs) on the viability and induction of apoptosis in Jurkat cells and to evaluate apoptosis signaling pathways. In this study, Jurkat cells were transfected with specific PTPN22 siRNA. Relative PTPN22 mRNA expression was measured by Quantitative Real-time PCR. Western blotting was performed to determine the protein levels of PTPN22, AKT, P-AKT, ERK, and P-ERK. The cytotoxic effects of PTPN22 siRNA were determined using the MTT assay...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27926878/the-csk-associated-adaptor-pag-inhibits-effector-t-cell-activation-in-cooperation-with-phosphatase-ptpn22-and-dok-adaptors
#8
Dominique Davidson, Ming-Chao Zhong, Pier Paolo Pandolfi, Silvia Bolland, Ramnik J Xavier, Brian Seed, Xin Li, Hua Gu, André Veillette
The transmembrane adaptor PAG (Cbp) has been proposed to mediate membrane recruitment of Csk, a cytoplasmic protein tyrosine kinase playing a critical inhibitory role during T cell activation, by inactivating membrane-associated Src kinases. However, this model has not been validated by genetic evidence. Here, we demonstrate that PAG-deficient mice display enhanced T cell activation responses in effector, but not in naive, T cells. PAG-deficient mice also have augmented T cell-dependent autoimmunity and greater resistance to T cell anergy...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27917628/association-between-ptpn22-ctla-4-gene-polymorphism-and-allergic-rhinitis-with-asthma-in-children
#9
Shang Hua Song, Xiao Qiang Wang, Yang Shen, Su Ling Hong, Xia Ke
Allergic rhinitis (AR) is an IgE-mediated upper airway disease, and its impact on asthma has been widely recognized. Protein tyrosine phosphatase non-receptor 22 (PTPN22) gene and the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms have been reported to be associated with several immune-related diseases. Here we investigated the reffect of these two genes' polymorphisms on the risk of AR and asthma in Chinese Han children. A total of 106 AR patients, 112 AR with asthma patients, and 109 healthy children were enrolled in the study...
October 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27917411/ptpn22-inhibition-resets-defective-human-central-b-cell-tolerance
#10
Jean-Nicolas Schickel, Marcel Kuhny, Alessia Baldo, Jason M Bannock, Christopher Massad, Haowei Wang, Nathan Katz, Tyler Oe, Laurence Menard, Pauline Soulas-Sprauel, Till Strowig, Richard Flavell, Eric Meffre
The 1858T protein tyrosine phosphatase nonreceptor type 22 (PTPN22 T) allele is one of the main risk factors associated with many autoimmune diseases and correlates with a defective removal of developing autoreactive B cells in humans. To determine whether inhibiting PTPN22 favors the elimination of autoreactive B cells, we first demonstrated that the PTPN22 T allele interfered with the establishment of central B cell tolerance using NOD-scid-common γ chain knockout (NSG) mice engrafted with human hematopoietic stem cells expressing this allele...
2016: Science Immunology
https://www.readbyqxmd.com/read/27906052/antibody-responses-to-de-novo-identified-citrullinated-fibrinogen-peptides-in-rheumatoid-arthritis-and-visualization-of-the-corresponding-b-cells
#11
Vijay Joshua, Loes Schobers, Philip J Titcombe, Lena Israelsson, Johan Rönnelid, Monika Hansson, Anca I Catrina, Ger J M Pruijn, Vivianne Malmström
BACKGROUND: Antibodies against citrullinated proteins (ACPA) are common in patients with rheumatoid arthritis (RA). ACPA can appear before disease onset and target many self-antigens. Citrullinated fibrin/fibrinogen represents a classical ACPA target antigen, and mass spectrometry of RA synovial fluid reveals elevated citrullinated (cit) fibrinogen (Fib) peptides compared to non-RA controls. We investigated the extent to which these less-studied peptides represent autoantibody targets and sought to visualize the corresponding cit-Fib-reactive B cells in RA patients...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27892782/c1858t-polymorphism-of-protein-tyrosine-phosphatase-non-receptor-type-22-ptpn22-an-eligible-target-for-prevention-of-type-1-diabetes
#12
Giovanni Prezioso, Laura Comegna, Concetta Di Giulio, Simone Franchini, Francesco Chiarelli, Annalisa Blasetti
In type 1 diabetes (T1D), several genetic factors are associated to β-cell autoimmunity onset and clinical progression. HLA-genes play a major role in susceptibility and initiation of β-cell autoimmunity, whereas non-HLA genes may influence the destruction rate. Areas covered: Our review focuses on the possible role of the PTPN22 C1858 T variant as a prognostic factor, given its influence on disease variability. Moreover, we present the potential role of C1858 T as a target for tertiary prevention trials and new therapeutic strategies, such as the LYP inhibitors...
December 8, 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27888068/associations-of-single-nucleotide-polymorphisms-of-ptpn22-and-ctla4-genes-with-the-risk-of-allergic-rhinitis-in-a-chinese-han-population
#13
Xia Ke, Shanghua Song, Xiaoqiang Wang, Yang Shen, Houyong Kang, Suling Hong
BACKGROUND: Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Protein tyrosine phosphatase non-receptor 22 encoded by PTPN22 gene and cytotoxic T-lymphocyte associated 4 encoded by Ctla4 gene are associated with autoimmune diseases. PURPOSE: This study was performed to evaluate the potential association of PTPN22 and Ctla4 single nucleotide polymorphisms (SNPs) with AR in a Chinese Han population. METHODS: A case-control study was performed in 783 Chinese AR patients and 811 healthy controls...
February 2017: Human Immunology
https://www.readbyqxmd.com/read/27878451/beyond-genetics-what-causes-type-1-diabetes
#14
REVIEW
Zhen Wang, Zhiguo Xie, Qianjin Lu, Christopher Chang, Zhiguang Zhou
Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell-mediated β cell destruction in the pancreas of genetically susceptible individuals. Extensive familial and population genetic studies uncovered the strong linkage and association between HLA gene variants and T1D. Non-HLA genes have also been associated with T1D, such as INS, CTLA4, and PTPN22. T1D is considered as one of the most heritable common diseases. However, evidence that monozygotic twins have incomplete concordance of disease susceptibility provides convincing proof that environmental factors also play important roles in the pathogenesis of the disease...
April 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/27866840/the-role-of-human-leukocyte-antigen-drb1-dqb1-haplotypes-in-the-susceptibility-to-acquired-idiopathic-thrombotic-thrombocytopenic-purpura
#15
György Sinkovits, Ágnes Szilágyi, Péter Farkas, Dóra Inotai, Anikó Szilvási, Attila Tordai, Katalin Rázsó, Marienn Réti, Zoltán Prohászka
The acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying ADAMTS13-deficiency is caused by inhibitory autoantibodies against the protease. Human leukocyte antigens (HLA), responsible for antigen presentation, play an important role in the development of antibodies. The loci coding HLA DR and DQ molecules are inherited in linkage as haplotypes. The c.1858C>T polymorphism of the PTPN22 gene, which codes a protein tyrosine phosphatase important in lymphocyte activation, predisposes to a number of autoimmune diseases...
February 2017: Human Immunology
https://www.readbyqxmd.com/read/27847023/protein-tyrosine-phosphatase-nonreceptor-type-22-ptpn22-gene-polymorphism-in-pulmonary-tuberculosis-in-the-indian-population
#16
Vydyanath R Narasimha, Kalpana Panati, M Gangadhara Reddy, Venkata Ramireddy Narala
A variant of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene is known to be associated with susceptibility to autoimmune diseases and bacterial infections as it acts as an important regulator of T-cell activation. The objective of this study was to evaluate whether PTPN22-C1858T polymorphism is associated with the resistance to pulmonary tuberculosis (PTB). Single-nucleotide polymorphism of PTPN22-C1858T (rs2476601) was genotyped in 124 patients with PTB and 130 healthy controls from India using restriction fragment length polymorphism and direct sequencing of the amplified DNA...
September 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27807193/ptpn22-is-a-critical-regulator-of-fc%C3%AE-receptor-mediated-neutrophil-activation
#17
Sonja Vermeren, Katherine Miles, Julia Y Chu, Donald Salter, Rose Zamoyska, Mohini Gray
Neutrophils act as a first line of defense against bacterial and fungal infections, but they are also important effectors of acute and chronic inflammation. Genome-wide association studies have established that the gene encoding the protein tyrosine phosphatase nonreceptor 22 (PTPN22) makes an important contribution to susceptibility to autoimmune disease, notably rheumatoid arthritis. Although PTPN22 is most highly expressed in neutrophils, its function in these cells remains poorly characterized. We show in this article that neutrophil effector functions, including adhesion, production of reactive oxygen species, and degranulation induced by immobilized immune complexes, were reduced in Ptpn22(-/-) neutrophils...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27801679/nlrp3-tyrosine-phosphorylation-is-controlled-by-protein-tyrosine-phosphatase-ptpn22
#18
Marianne R Spalinger, Stephanie Kasper, Claudia Gottier, Silvia Lang, Kirstin Atrott, Stephan R Vavricka, Sylvie Scharl, Tina Raselli, Isabelle Frey-Wagner, Petrus M Gutte, Markus G Grütter, Hans-Dietmar Beer, Emmanuel Contassot, Andrew C Chan, Xuezhi Dai, David J Rawlings, Florian Mair, Burkhard Becher, Werner Falk, Michael Fried, Gerhard Rogler, Michael Scharl
No abstract text is available yet for this article.
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27799548/ptpn22-contributes-to-exhaustion-of-t-lymphocytes-during-chronic-viral-infection
#19
Christian J Maine, John R Teijaro, Kristi Marquardt, Linda A Sherman
The protein encoded by the autoimmune-associated protein tyrosine phosphatase nonreceptor type 22 gene, PTPN22, has wide-ranging effects in immune cells including suppression of T-cell receptor signaling and promoting efficient production of type I interferons (IFN-I) by myeloid cells. Here we show that mice deficient in PTPN22 resist chronic viral infection with lymphocytic choriomeningitis virus clone 13 (LCMV cl13). The numbers and function of viral-specific CD4 T lymphocytes is greatly enhanced, whereas expression of the IFNβ-induced IL-2 repressor, cAMP-responsive element modulator (CREM) is reduced...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27777982/a-molecular-signature-of-preclinical-rheumatoid-arthritis-triggered-by-dysregulated-ptpn22
#20
Hui-Hsin Chang, Guang-Yaw Liu, Nishant Dwivedi, Bo Sun, Yuko Okamoto, Jennifer D Kinslow, Kevin D Deane, M Kristen Demoruelle, Jill M Norris, Paul R Thompson, Jeffrey A Sparks, Deepak A Rao, Elizabeth W Karlson, Hui-Chih Hung, V Michael Holers, I-Cheng Ho
A unique feature of rheumatoid arthritis (RA) is the presence of anti-citrullinated protein antibodies (ACPA). Several risk factors for RA are known to increase the expression or activity of peptidyl arginine deiminases (PADs), which catalyze citrullination and, when dysregulated, can result in hypercitrullination. However, the consequence of hypercitrullination is unknown and the function of each PAD has yet to be defined. Th cells of RA patients are hypoglycolytic and hyperproliferative due to impaired expression of PFKFB3 and ATM, respectively...
October 20, 2016: JCI Insight
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