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https://www.readbyqxmd.com/read/28444099/association-of-the-protein-tyrosine-phosphatase-non-receptor-22-polymorphism-ptpn22-with-endometriosis-a-meta-analysis
#1
Noel Pabalan, Hamdi Jarjanazi, Denise Maria Christofolini, Bianca Bianco, Caio Parente Barbosa
Objective: To evaluate PTPN22 C1858T polymorphism and the risk of endometriosis. Methods: A meta-analysis of 10 published case-control studies (from four articles), with a total sample of 971 cases and 1,181 controls, was performed. We estimated risk (odds ratio and 95% confidence intervals) of endometriosis associations with the C1858T polymorphism. Results: A significant increased risk in all genetic models of the variant T allele with endometriosis (odds ratio: 3...
January 2017: Einstein
https://www.readbyqxmd.com/read/28439269/genome-wide-identification-of-target-genes-for-the-key-b-cell-transcription-factor-ets1
#2
Prontip Saelee, Alyssa Kearly, Stephen L Nutt, Lee Ann Garrett-Sinha
BACKGROUND: The transcription factor Ets1 is highly expressed in B lymphocytes. Loss of Ets1 leads to premature B cell differentiation into antibody-secreting cells (ASCs), secretion of autoantibodies, and development of autoimmune disease. Despite the importance of Ets1 in B cell biology, few Ets1 target genes are known in these cells. RESULTS: To obtain a more complete picture of the function of Ets1 in regulating B cell differentiation, we performed Ets1 ChIP-seq in primary mouse B cells to identify >10,000-binding sites, many of which were localized near genes that play important roles in B cell activation and differentiation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28438156/relative-contribution-of-type-1-and-type-2-diabetes-loci-to-the-genetic-etiology-of-adult-onset-non-insulin-requiring-autoimmune-diabetes
#3
Rajashree Mishra, Alessandra Chesi, Diana L Cousminer, Mohammad I Hawa, Jonathan P Bradfield, Kenyaita M Hodge, Vanessa C Guy, Hakon Hakonarson, Didac Mauricio, Nanette C Schloot, Knud B Yderstræde, Benjamin F Voight, Stanley Schwartz, Bernhard O Boehm, Richard David Leslie, Struan F A Grant
BACKGROUND: In adulthood, autoimmune diabetes can present as non-insulin-requiring diabetes, termed as 'latent autoimmune diabetes in adults' (LADA). In this study, we investigated established type 1 diabetes (T1D) and type 2 diabetes (T2D) genetic loci in a large cohort of LADA cases to assess where LADA is situated relative to these two well-characterized, classic forms of diabetes. METHODS: We tested the association of T1D and T2D GWAS-implicated loci in 978 LADA cases and 1057 non-diabetic controls of European ancestry using a linear mixed model...
April 25, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28437437/use-of-short-interfering-rna-delivered-by-cationic-liposomes-to-enable-efficient-down-regulation-of-ptpn22-gene-in-human-t-lymphocytes
#4
Valentina Perri, Marsha Pellegrino, Francesca Ceccacci, Anita Scipioni, Stefania Petrini, Elena Gianchecchi, Anna Lo Russo, Serena De Santis, Giovanna Mancini, Alessandra Fierabracci
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target...
2017: PloS One
https://www.readbyqxmd.com/read/28430763/protective-effect-of-pinitol-against-inflammatory-mediators-of-rheumatoid-arthritis-via-inhibition-of-protein-tyrosine-phosphatase-non-receptor-type-22-ptpn22
#5
Kewen Zheng, Zhixuan Zhao, Na Lin, Yiyan Wu, Ying Xu, Wanli Zhang
BACKGROUND The aim of the current study was to explore the anti-arthritic effect of pinitol via assessing its effect on various inflammatory mediators and its possible mechanism of action. MATERIAL AND METHODS We assessed the anti-arthritic effect of pinitol in a formaldehyde- and CFA-induced arthritic model in Wistar Swiss albino strain rats divided into 6 groups. The rats received different doses of pinitol and indomethacin for 28 days. The arthritic index and body weight were determined at regular intervals, together with hepatic, hematological, and antioxidant parameters...
April 21, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28424905/association-of-stat4-rs7574865-and-ptpn22-rs2476601-polymorphisms-with-rheumatoid-arthritis-and-non-systemically-reacting-antibodies-in-egyptian-patients
#6
Dalia El-Lebedy, Hala Raslan, Alshaymaa Ibrahim, Ingy Ashmawy, Shereen Abd El-Aziz, Asmaa M Mohammed
The aim of this study was to investigate association of protein tyrosine phosphatase non-receptor type 22 (PTPN22) rs2476601 and signal transducer and activator of transcription 4 (STAT4) rs7574865 polymorphisms with rheumatoid arthritis (RA) susceptibility and to assess potential association with the status of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, serum neopterin, and disease activity. RF, anti-CCP antibodies, and neopterin were assayed in serum of 100 unrelated RA patients and 114 controls...
April 19, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28375784/ptpn22-single-nucleotide-polymorphisms-in-iranian-patients-with-type-1-diabetes-mellitus
#7
Farzaneh Abbasi, Samaneh Soltani, Amene Saghazadeh, Ehsan Soltaninejad, Arezou Rezaei, Alireza Zare Bidoki, Tayyeb Bahrami, Ali Akbar Amirzargar, Nima Rezaei
BACKGROUND: PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases, including type 1 diabetes (T1D) which is a T-cell-mediated disease. OBJECTIVE: The present study was aimed at genotyping of an Iranian population for five polymorphisms of the PTPN22 gene. METHODS: The study population consisted of 99 T1D patients and 100 healthy controls...
April 4, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28364254/characterisation-of-rapid-progressors-to-type-1-diabetes-among-children-with-hla-conferred-disease-susceptibility
#8
Petra M Pöllänen, Johanna Lempainen, Antti-Pekka Laine, Jorma Toppari, Riitta Veijola, Paula Vähäsalo, Jorma Ilonen, Heli Siljander, Mikael Knip
AIMS/HYPOTHESIS: In this study, we aimed to characterise rapid progressors to type 1 diabetes among children recruited from the general population, on the basis of HLA-conferred disease susceptibility. METHODS: We monitored 7410 HLA-predisposed children participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study for the development of beta cell autoimmunity and type 1 diabetes from birth over a median follow-up time of 16.2 years (range 0...
March 31, 2017: Diabetologia
https://www.readbyqxmd.com/read/28291534/ptpn22-1123g-c-polymorphism-and-anti-cyclic-citrullinated-protein-antibodies-in-rheumatoid-arthritis
#9
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
#10
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
#11
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
#12
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
#13
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-antineutrophil-cytoplasmic-autoantibody-associated-vasculitis
#14
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 causal and biologic mechanisms of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: A genome-wide association study and subsequent replication study were conducted in a total cohort of 1,986 cases of AAV (patients with granulomatosis with polyangiitis [Wegener's] [GPA] or microscopic polyangiitis [MPA]) and 4,723 healthy controls. Meta-analysis of these data sets and functional annotation of identified risk loci were performed, and candidate disease variants with unknown functional effects were investigated for their 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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