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https://www.readbyqxmd.com/read/27917628/association-between-ptpn22-ctla-4-gene-polymorphism-and-allergic-rhinitis-with-asthma-in-children
#1
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
#2
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
#3
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
#4
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 C1858T variant as a prognostic factor, given its influence on disease variability. Moreover, we present the potential role of C1858T as a target for tertiary prevention trials and new therapeutic strategies, such as the LYP inhibitors...
November 28, 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
#5
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...
November 22, 2016: Human Immunology
https://www.readbyqxmd.com/read/27878451/beyond-genetics-what-causes-type-1-diabetes
#6
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...
November 22, 2016: 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
#7
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...
November 17, 2016: Human Immunology
https://www.readbyqxmd.com/read/27847023/protein-tyrosine-phosphatase-nonreceptor-type-22-ptpn22-gene-polymorphism-in-pulmonary-tuberculosis-in-the-indian-population
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27751376/the%C3%A2-1858%C3%A2-c-t-polymorphism-in-the-ptpn22-gene-is-associated-with-cystic-fibrosis-patients-in-northeast-mexico
#13
Mauricio A Salinas-Santander, Elizabeth Bazan-Mendoza, Marisol Espinoza-Ruiz, Rocio Ortiz-Lopez, Adriana Bustamante, Celia N Sanchez-Dominguez
Cystic fibrosis (CF) is the most common autosomal recessive disease in the Caucasian population, but it has also been widely diagnosed in the Mexican population. Production of viscous secretions affects the secretory epithelia and the respiratory condition usually leads to death. The relationship between the CFTR genotype and the disease phenotype is not well understood. Other risk factors such as genetic and autoimmune influence the development of this disease. We analyzed the PTPN22 R620W polymorphism (+1858 C/T, rs2476601) in 78 DNA samples from CF patients and 232 healthy controls from northeast Mexico using the polymerase chain reaction-restriction fragment length (PCR-RFLP) method...
July 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/27744395/rheumatoid-arthritis-and-coronary-artery-disease-genetic-analyses-do-not-support-a-causal-relation
#14
Henning Jansen, Christina Willenborg, Wolfgang Lieb, Lingyao Zeng, Paola Gloria Ferrario, Christina Loley, Inke R König, Jeanette Erdmann, Nilesh J Samani, Heribert Schunkert
OBJECTIVE: Inflammatory diseases, specifically rheumatoid arthritis (RA), are assumed to increase the risk of coronary artery disease (CAD). More recently, multiple single-nucleotide polymorphisms (SNP) associated with RA risk were identified. If causal mechanisms affecting risks of RA and CAD are overlapping, risk alleles for RA might also increase the risk of CAD. METHODS: Sixty-one SNP associating with RA in genome-wide significant analyses were tested for association with CAD in CARDIoGRAM (Coronary ARtery DIsease Genome wide Replication and Meta-analysis), a metaanalysis including genome-wide association data (22,233 CAD cases, 64,762 controls)...
October 15, 2016: Journal of Rheumatology
https://www.readbyqxmd.com/read/27732119/association-of-ptpn22-gene-polymorphisms-with-susceptibility-to-juvenile-idiopathic-arthritis-in-iranian-population
#15
Tayyeb Bahrami, Samaneh Soltani, Kasra Moazzami, Mir Saeed Yekaninejad, Arash Salmaninejad, Ehsan Soltaninejad, Vahid Ziaee, Nima Rezaei
Juvenile idiopathic arthritis (JIA), the most common cause of chronic arthritis in children, is a complex immune-mediated disease with considerable long-term morbidity and mortality. According to previous studies, PTPN22 gene has been associated with JIA in several populations. In the present study, we attempted to determine the association of PTPN22 single nucleotide polymorphisms (SNPs) with susceptibility to JIA in Iranian population. Using the Real-time PCR allelic discrimination method, samples consisting of 55 unrelated patients and 93 healthy controls were genotyped...
October 12, 2016: Fetal and Pediatric Pathology
https://www.readbyqxmd.com/read/27725666/protein-tyrosine-phosphatase-ptpn22-has-dual-roles-in-promoting-pathogen-versus-homeostatic-driven-cd8-t-cell-responses
#16
Tatiana Jofra, Roberta Di Fonte, Tarun Edgar Hutchinson, Farhad Dastmalchi, Giuseppe Galvani, Manuela Battaglia, Shahram Salek-Ardakani, Georgia Fousteri
PTPN22 (protein tyrosine phosphatase non receptor 22) encodes a tyrosine phosphatase that functions as a key regulator of immune homeostasis. In particular, PTPN22 inhibits T-cell receptor signaling and selectively promotes type I interferon responses in myeloid cells. To date, there is little information on the CD8 T-cell-intrinsic role of PTPN22 in response to a viral pathogen. We unexpectedly found that PTPN22-deficient virus-specific CD8 T cells failed to accumulate in wild-type hosts after lymphocytic choriomeningitis virus infection...
October 11, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27716086/association-of-cd247-cd3%C3%AE-gene-polymorphisms-with-t1d-and-aitd-in-the-population-of-northern-sweden
#17
Dan Holmberg, Karin Ruikka, Petter Lindgren, Mats Eliasson, Sofia Mayans
BACKGROUND: T1D and AITD are autoimmune disorders commonly occurring in the same family and even in the same individual. The genetic contribution to these disorders is complex making uncovering of susceptibility genes very challenging. The general aim of this study was to identify loci and genes contributing to T1D/AITD susceptibility. Our strategy was to perform linkage and association studies in the relatively genetically homogenous population of northern Sweden. We performed a GWLS to find genomic regions linked to T1D/AITD in families from northern Sweden and we performed an association study in the families to test for association between T1D/AITD and variants in previously published candidate genes as well as a novel candidate gene, CD247...
October 4, 2016: BMC Medical Genetics
https://www.readbyqxmd.com/read/27703032/superresolution-imaging-of-the-cytoplasmic-phosphatase-ptpn22-links-integrin-mediated-t-cell-adhesion-with-autoimmunity
#18
Garth L Burn, Georgina H Cornish, Katarzyna Potrzebowska, Malin Samuelsson, Juliette Griffié, Sophie Minoughan, Mark Yates, George Ashdown, Nicolas Pernodet, Vicky L Morrison, Cristina Sanchez-Blanco, Harriet Purvis, Fiona Clarke, Rebecca J Brownlie, Timothy J Vyse, Rose Zamoyska, Dylan M Owen, Lena M Svensson, Andrew P Cope
Integrins are heterodimeric transmembrane proteins that play a fundamental role in the migration of leukocytes to sites of infection or injury. We found that protein tyrosine phosphatase nonreceptor type 22 (PTPN22) inhibits signaling by the integrin lymphocyte function-associated antigen-1 (LFA-1) in effector T cells. PTPN22 colocalized with its substrates at the leading edge of cells migrating on surfaces coated with the LFA-1 ligand intercellular adhesion molecule-1 (ICAM-1). Knockout or knockdown of PTPN22 or expression of the autoimmune disease-associated PTPN22-R620W variant resulted in the enhanced phosphorylation of signaling molecules downstream of integrins...
October 4, 2016: Science Signaling
https://www.readbyqxmd.com/read/27638722/genetic-markers-as-therapeutic-target-in-rheumatoid-arthritis-a-game-changer-in-clinical-therapy
#19
A M Mohamed Thoufic Ali, S Vino
Rheumatoid arthritis (RA) is a chronic, inflammatory, multi-systemic autoimmune disease unremitted by genetic and environmental factors. The factors are crucial but inadequate in the development of disease; however, these factors can be representative of potential therapeutic targets and response to clinical therapy. Insights into the contribution of genetic risk factors are currently in progress with studies querying the genetic variation, their role in gene expression of coding and non-coding genes and other mechanisms of disease...
November 2016: Rheumatology International
https://www.readbyqxmd.com/read/27615679/coincidence-of-ptpn22-c-1858cc-and-fcrl3-169cc-genotypes-as-a-biomarker-of-preserved-residual-%C3%AE-cell-function-in-children-with-type-1-diabetes
#20
Małgorzata Pawłowicz, Rafał Filipów, Grzegorz Krzykowski, Anna Stanisławska-Sachadyn, Lucyna Morzuch, Julia Kulczycka, Anna Balcerska, Janusz Limon
BACKGROUND: Genotype-phenotype studies in type 1 diabetes (T1DM) patients are needed for further development of therapy strategies. OBJECTIVE: Our aims were to investigate the distribution of selected PTPN22 and FCRL3 gene polymorphisms and their associations with clinical course of disease in children with newly diagnosed T1DM from the Pomeranian region of Poland. SUBJECTS/METHODS: The prospective, longitudinal study of 147 children with newly diagnosed T1DM-autoimmune subtype was conducted...
September 12, 2016: Pediatric Diabetes
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