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https://www.readbyqxmd.com/read/28701508/prdm1-regulates-thymic-epithelial-function-to-prevent-autoimmunity
#1
Natalie A Roberts, Brian D Adams, Nicholas I McCarthy, Reuben M Tooze, Sonia M Parnell, Graham Anderson, Susan M Kaech, Valerie Horsley
Autoimmunity is largely prevented by medullary thymic epithelial cells (TECs) through their expression and presentation of tissue-specific Ags to developing thymocytes, resulting in deletion of self-reactive T cells and supporting regulatory T cell development. The transcription factor Prdm1 has been implicated in autoimmune diseases in humans through genome-wide association studies and in mice using cell type-specific deletion of Prdm1 in T and dendritic cells. In this article, we demonstrate that Prdm1 functions in TECs to prevent autoimmunity in mice...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28628673/multiple-tolerance-defects-contribute-to-the-breach-of-b-cell-tolerance-in-new-zealand-black-chromosome-1-congenic-mice
#2
Nan-Hua Chang, Kieran P Manion, Christina Loh, Evelyn Pau, Yuriy Baglaenko, Joan E Wither
Lupus is characterized by a loss of B cell tolerance leading to autoantibody production. In this study, we explored the mechanisms underlying this loss of tolerance using B6 congenic mice with an interval from New Zealand Black chromosome 1 (denoted c1(96-100)) sufficient for anti-nuclear antibody production. Transgenes for soluble hen egg white lysozyme (sHEL) and anti-HEL immunoglobulin were crossed onto this background and various tolerance mechanisms examined. We found that c1(96-100) mice produced increased levels of IgM and IgG anti-HEL antibodies compared to B6 mice and had higher proportions of germinal center B cells and long-lived plasma cells, suggesting a germinal center-dependent breach of B cell anergy...
2017: PloS One
https://www.readbyqxmd.com/read/28628475/predictive-autoimmunity-using-autoantibodies-screening-for-anti-nuclear-antibodies
#3
Dolores Pérez, Boris Gilburd, Óscar Cabrera-Marante, Jose A Martínez-Flores, Manuel Serrano, Laura Naranjo, Daniel Pleguezuelo, Luis Morillas, Ora Shovman, Estela Paz-Artal, Yehuda Shoenfeld, Antonio Serrano
BACKGROUND: Early detection of antinuclear antibodies (ANA) in asymptomatic subjects is useful to predict autoimmune diseases years before diagnosis. ANA have been determined by indirect immunofluorescence (IIF) using human epithelial type 2 (HEp-2) cells, which is considered the gold standard technique. Multiplex technology (BioPlex ANA Screen) has been introduced for ANA evaluation in recent years. Nevertheless, concordance between BioPlex and IIF is low and there is no harmonization between both methods for detection of autoantibodies...
June 17, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28620656/oxidative-t-cell-modifications-in-lupus-and-sjogren-s-syndrome
#4
F M Strickland, T Mau, M O'Brien, A Ghosh, B C Richardson, R Yung
OBJECTIVES: Lupus flares are triggered by environmental agents that cause oxidative stress, but the mechanisms involved are unclear. The flares are characterized by oxidative modifications of proteins by 4-hydroxynonenals, malondialdehydes, carbonyls and nitration. These modifications have been proposed to induce and perpetuate lupus flares by "altered self" mechanisms. An epigenetically altered CD4+CD28+ T cell subset, caused at least in part by nitration of T cell signaling molecules, is found in patients with active lupus, and nitrated T cells are sufficient to cause lupus-like autoimmunity in animal models...
April 2017: Lupus (Los Angeles)
https://www.readbyqxmd.com/read/28590340/colonic-phenotypes-are-associated-with-poorer-response-to-anti-tnf-therapies-in-patients-with-ibd
#5
Soon Man Yoon, Talin Haritunians, Sultan Chhina, Zhenqiu Liu, Shaohong Yang, Carol Landers, Dalin Li, Byong Duk Ye, David Shih, Eric A Vasiliauskas, Andrew Ippoliti, Shervin Rabizadeh, Stephan R Targan, Gil Y Melmed, Dermot P B McGovern
BACKGROUND: Although anti-tumor necrosis factor (TNF) agents are effective in patients with inflammatory bowel disease (IBD), many patients either do not respond to anti-TNF treatment or lose response over time. The aim of this study was to determine factors associated with response to anti-TNF therapy in IBD. METHODS: Patients with Crohn's disease (CD) or ulcerative colitis who had consented to participate in a genetics registry and been treated with anti-TNF agents were evaluated retrospectively and categorized as primary nonresponders or secondary nonresponders...
August 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28587625/anti-nuclear-autoantibodies-in-the-general-german-population-prevalence-and-lack-of-association-with-selected-cardiovascular-and-metabolic-disorders-findings-of-a-multicenter-population-based-study
#6
Manas K Akmatov, Nadja Röber, Wolfgang Ahrens, Dieter Flesch-Janys, Julia Fricke, Halina Greiser, Kathrin Günther, Rudolf Kaaks, Yvonne Kemmling, Bastian Krone, Jakob Linseisen, Christa Meisinger, Susanne Moebus, Nadia Obi, Carlos A Guzman, Karsten Conrad, Frank Pessler
BACKGROUND: We determined the prevalence of anti-nuclear autoantibodies (ANAs) in the German adult population and examined the association between ANAs and cardiovascular and metabolic disorders. METHODS: We used data and blood samples from the pretest phases of the German National Cohort, obtained from six of the 18 study centers (n = 1199). All centers applied standardized instruments including face-to-face interviews, anthropometric measurements and collection of blood samples...
June 6, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28587585/the-impact-of-biological-treatments-on-the-anti-dsdna-and-anti-nucleosome-tests
#7
M Infantino, V Grossi, M Benucci, F Li Gobbi, A Damiani, M Manfredi
Background Anti-double stranded DNA antibodies are a very heterogeneous group of antibodies, quite specific for systemic lupus erythematosus. Newer technologies, such as addressable laser bead immunoassays (ALBIA), show great potential as a diagnostic application. The production of anti-double stranded DNA antibodies is often encountered in inflammatory arthritis; however, literature reports that the actual onset of drug induced lupus in patients treated with biological drugs is a rare event. False positive results for anti-double stranded DNA and anti-nucleosome antibodies detected in patients with inflammatory arthritis treated with different biologics prompted the investigation of full autoantibody profiles to evaluate each biomarker's diagnostic performance in systemic lupus erythematosus...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28565826/transcriptional-profiling-of-leukocytes-from-rheumatoid-arthritis-patients-before-and-after-anti-tumor-necrosis-factor-therapy-a-comparison-of-anti-nuclear-antibody-positive-and-negative-subsets
#8
Laurie S Davis, Andreas M Reimold
Anti-nuclear antibodies (ANAs) may be induced in patients with rheumatoid arthritis (RA) receiving anti-tumor necrosis factor (TNF) therapy with TNF inhibitors (TNFi), etanercept, infliximab or adalimumab. In the present study, 11 patients who were TNFi drug naive were started on TNFi at a time of high disease activity. Of these, all cases were positive for rheumatoid factor and 9 cases tested were positive for anti-citrullinated peptide (anti-CCP) antibodies prior to TNFi treatment. Peripheral blood mononuclear cells (PBMCs) and serum were collected from all patients before and after TNFi therapy...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28544593/performance-of-anti-nuclear-antibodies-for-classifying-systemic-lupus-erythematosus-a-systematic-literature-review-and-meta-regression-of-diagnostic-data
#9
Nicolai Leuchten, Annika Hoyer, Ralph Brinks, Monika Schoels, Matthias Schneider, Josef Smolen, Sindhu R Johnson, David Daikh, Thomas Dörner, Martin Aringer, George Bertsias
OBJECTIVE: To review the published literature on the performance of indirect immunofluorescence (IIF)-HEp-2 ANA testing for classification of SLE. METHODS: A systematic literature search was conducted in the MEDLINE, EMBASE and COCHRANE databases for articles published between January 1990 and October 2015. The research question was structured according to PICO (Population, Intervention, Comparator, Outcome) format rules, and PRISMA recommendations were followed where appropriate...
May 23, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28532574/prevalence-and-correlates-of-hepatitis-c-virus-associated-inflammatory-arthritis-in-a-population-based-cohort
#10
Elizabeth D Ferucci, Tammy L Choromanski, Danielle T Varney, Holly S Ryan, Lisa J Townshend-Bulson, Brian J McMahon, Mark H Wener
OBJECTIVES: The objectives of this study were to determine the prevalence of hepatitis C virus-associated inflammatory arthritis, to describe its clinical and immunologic correlates, and to identify features that are characteristic of arthritis in chronic hepatitis C. METHODS: Participants with chronic hepatitis C infection enrolled in a population-based cohort study in Alaska and who had not received anti-viral treatment for hepatitis C were recruited. In a cross-sectional study, we assessed joint symptoms and signs, performed autoantibody and cytokine testing, and abstracted medical records for features of hepatitis C and arthritis...
April 24, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28526333/systemic-manifestations-of-primary-sj%C3%A3-gren-s-syndrome-in-the-nod-b10sn-h2-b-j-mouse-model
#11
Jeremy Kiripolsky, Long Shen, Yichen Liang, Alisa Li, Lakshmanan Suresh, Yun Lian, Quan-Zhen Li, Daniel P Gaile, Jill M Kramer
Animal models that recapitulate human disease are crucial for the study of Sjögren's Syndrome (SS). While several SS mouse models exist, there are few primary SS (pSS) models that mimic systemic disease manifestations seen in humans. Similar to pSS patients, NOD.B10Sn-H2(b)/J (NOD.B10) mice develop exocrine gland disease and anti-nuclear autoantibodies. However, the disease kinetics and spectrum of extra-glandular disease remain poorly characterized in this model. Our objective was to characterize local and systemic SS manifestations in depth in NOD...
May 17, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28515509/anti-nuclear-cytoplasmic-antibody-associated-vasculitis-a-probable-adverse-effect-of-sofosbuvir-treatment-in-chronic-hepatitis-c-patients
#12
Youssef K Ahmad, Salwa Tawfeek, Mohamed Sharaf-Eldin, Hassan E Elbatea, Abdelrahman Kobtan, Ferial El-Kalla, Rehab Badawi, Sherief Abd-Elsalam
Background: Egypt has the largest hepatitis C virus (HCV) epidemic worldwide. Sofosbuvir is an antiviral drug acting by inhibition of the HCV NS5B polymerase. It has shown high efficacy in combination with several other drugs and has a low reported rate of side effects. Objective: The aim of this prospective cohort study was to assess the safety of sofosbuvir-based treatment regimens used to treat chronic hepatitis C infections and to detect any side effects of sofosbuvir not previously reported. Methods: We studied treatment side effects in 3,000 patients with chronic HCV infection treated with sofosbuvir and ribavirin for 24 weeks or treated by pegylated interferon, sofosbuvir, and ribavirin triple therapy for 12 weeks...
April 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/28502960/circulating-anti-nuclear-antibodies-in-systemic-sclerosis-utility-in-diagnosis-and-disease-subsetting
#13
Masataka Kuwana
The presence of circulating anti-nuclear antibodies (ANAs) is a hallmark of immune dysregulation in patients with systemic sclerosis (SSc). Currently, a variety of SSc-specific ANAs, including anticentromere, anti-topoisomerase I, and anti-RNA polymerase III antibodies, have been well characterized, and their commercial kits are available worldwide. Since these autoantibodies are specifically detected in SSc patients and are associated with unique sets of disease manifestations, they are widely used in routine clinical practice for diagnosis, clinical subgrouping, and prediction of future organ involvements and prognosis...
2017: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
https://www.readbyqxmd.com/read/28468970/concomitant-disruption-of-cd4-and-cd8-genes-facilitates-the-development-of-double-negative-%C3%AE-%C3%AE-tcr-peripheral-t-cells-that-respond-robustly-to-staphylococcal-superantigen
#14
Vaidehi R Chowdhary, Ashton Krogman, Ashenafi Y Tilahun, Mariam P Alexander, Chella S David, Govindarajan Rajagopalan
Mature peripheral double negative T (DNT) cells expressing αβ TCR but lacking CD4/CD8 coreceptors play protective as well as pathogenic roles. To better understand their development and functioning in vivo, we concomitantly inactivated CD4 and CD8 genes in mice with intact MHC class I and class II molecules with the hypothesis that this would enable the development of DNT cells. We also envisaged that these DNT cells could be activated by bacterial superantigens in vivo as activation of T cells by superantigens does not require CD4 and CD8 coreceptors...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28418334/juvenile-idiopathic-arthritis
#15
Kenan Barut, Amra Adrovic, Sezgin Şahin, Özgür Kasapçopur
Juvenile idiopathic arthritis is the most common chronic rheumatic disease of unknown aetiology in childhood and predominantly presents with peripheral arthritis. The disease is divided into several subgroups, according to demographic characteristics, clinical features, treatment modalities and disease prognosis. Systemic juvenile idiopathic arthritis, which is one of the most frequent disease subtypes, is characterized by recurrent fever and rash. Oligoarticular juvenile idiopathic arthritis, common among young female patients, is usually accompanied by anti-nuclear antibodie positivity and anterior uveitis...
April 5, 2017: Balkan Medical Journal
https://www.readbyqxmd.com/read/28408984/b-cell-tolerance-and-autoimmunity
#16
REVIEW
Takeshi Tsubata
Self-reactive B cells are tolerized at various stages of B-cell development and differentiation, including the immature B-cell stage (central tolerance) and the germinal center (GC) B-cell stage, and B-cell tolerance involves various mechanisms such as deletion, anergy, and receptor editing. Self-reactive B cells generated by random immunoglobulin variable gene rearrangements are tolerized by central tolerance and anergy in the periphery, and these processes involve apoptosis regulated by Bim, a pro-apoptotic member of the Bcl-2 family, and regulation of B-cell signaling by various phosphatases, including SHIP-1 and SHP-1...
2017: F1000Research
https://www.readbyqxmd.com/read/28395724/-single-nucleotide-polymorphism-of-stat4-rs7574865-is-associated-with-the-susceptibility-of-primary-biliary-cirrhosis-in-han-population-of-partial-regions-of-jiangsu-province
#17
Liming Zheng, Hong Zhou
Objective To investigate the correlation of single nucleotide polymorphism (SNP) of signal transducer and activator of transcription 4 (STAT4) rs7574865 gene with primary biliary cirrhosis (PBC) in Han population of Jiangsu province. Methods The peripheral blood samples were collected from 138 inpatients with PBC and 116 unrelated healthy donors in the Third People's Hospital of Changzhou City in Jiangsu province. The STAT4 rs7574865 SNP was determined by polymerase chain reaction-sequence specific primer (PCR-SSP) assay...
April 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28384257/serum-th1-and-th17-related-cytokines-and-autoantibodies-in-patients-with-posner-schlossman-syndrome
#18
Jun Zhao, Wenchieh Chen, Xiaosheng Huang, Shiming Peng, Tianhui Zhu, Zhihui Deng, Ping Liang, Hui Chang, Bao Jian Fan
Posner-Schlossman syndrome (PSS) shares some clinical features with uveitis and open angle glaucoma. Cytokines and autoantibodies have been associated with uveitis and open angle glaucoma. However, the role of serum cytokines and autoantibodies in the pathogenesis of PSS remains unknown. This study aimed to evaluate the associations of type 1 T helper (Th1) and Th17 related cytokines and autoantibodies with PSS. Peripheral blood serum samples were collected from 81 patients with PSS and 97 gender- and age-matched healthy blood donors...
2017: PloS One
https://www.readbyqxmd.com/read/28367173/cognitive-dysfunction-in-patients-with-systemic-lupus-erythematosus
#19
Bilal Azeem Butt, Sumaira Farman, Saira Elaine Anwer Khan, Muhammad Ahmed Saeed, Nighat Mir Ahmad
OBJECTIVE: To determine the frequency of cognitive dysfunction in patients with Systemic Lupus Erythematosus in a Pakistani population, presenting at a tertiary care Rheumatology setting. METHODS: This cross-sectional study was conducted at the Division of Rheumatology, Fatima Memorial Hospital, Lahore, from March to June 2016. A total of 43 consecutive patients, who fulfilled the 2012 SLICC (Systemic Lupus International Collaborating Clinics) classification criteria for Systemic Lupus Erythematosus (SLE), were enrolled...
January 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28337388/the-clinical-significance-of-anti-mitotic-spindle-apparatus-antibody-msa-and-anti-centromere-antibody-aca-detected-in-patients-with-small-cell-lung-cancer-sclc
#20
Liming Tan, Yuhong Zhang, Yongqing Jiang, Hua Li, Juanjuan Chen, Feng Ming, Waimei Wang, Jianlin Yu, Tingting Zeng, Yongjian Tian, Yang Wu
PURPOSE: The project is aimed to detect anti-mitotic spindle apparatus antibody (MSA) and anti-centromere antibody (ACA) and explore the clinical value for the diagnosis of small cell lung cancer (SCLC), providing clinical evidence for molecular studies of SCLC. METHODS: 93 SCLC patients, 208 patients with other cancers and 50 healthy controls were enrolled in this study. MSA antibodies were detected by enzyme linked immunosorbent assay (ELISA). MSA, ACA and anti nuclear antibodies (ANA) were examined by indirect immuno-fluorescence (IIF)...
2017: American Journal of Clinical and Experimental Immunology
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