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Citrullinated peptides

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https://www.readbyqxmd.com/read/27912794/a-genetic-risk-score-composed-of-rheumatoid-arthritis-risk-alleles-hla-drb1-haplotypes-and-response-to-tnfi-therapy-results-from-a-swedish-cohort-study
#1
Xia Jiang, Johan Askling, Saedis Saevarsdottir, Leonid Padyukov, Lars Alfredsson, Sebastien Viatte, Thomas Frisell
BACKGROUND: To prevent debilitating and irreversible joint damage, rheumatoid arthritis (RA) is often treated with tumor necrosis factor inhibitor (TNFi), but many patients do not respond to this costly therapy. Few predictors for response are known, and it has been proposed that genetic factors which influence the development of RA may also influence disease severity and response to therapy. Several previous studies have attempted to confirm this but results remain inconclusive. We expand on previous studies by including more RA risk alleles, and maximize power by combining them into a genetic risk score...
December 3, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27912793/antibodies-against-carbamylated-proteins-and-cyclic-citrullinated-peptides-in-systemic-lupus-erythematosus-results-from-two-well-defined-european-cohorts
#2
Michael Ziegelasch, Myrthe A M van Delft, Philip Wallin, Thomas Skogh, César Magro-Checa, Gerda M Steup-Beekman, Leendert A Trouw, Alf Kastbom, Christopher Sjöwall
BACKGROUND: Articular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data...
December 3, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27909437/differentially-methylated-dna-regions-in-monozygotic-twin-pairs-discordant-for-rheumatoid-arthritis-an-epigenome-wide-study
#3
Anders J Svendsen, Kristina Gervin, Robert Lyle, Lene Christiansen, Kirsten Kyvik, Peter Junker, Christian Nielsen, Gunnar Houen, Qihua Tan
OBJECTIVES: In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA. METHODS: Genomic DNA was isolated from whole blood samples from 28 MZ twin pairs discordant for RA. DNA methylation was measured using the HumanMethylation450 BeadChips. Smoking, anti-cyclic citrullinated peptide antibodies, and immunosuppressive treatment were included as covariates...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27908754/cyclic-citrullinated-mbp87-99-peptide-stimulates-t-cell-responses-implications-in-triggering-disease
#4
Vasso Apostolopoulos, George Deraos, Minos-Timotheos Matsoukas, Stephanie Day, Lily Stojanovska, Theodore Tselios, Maria-Eleni Androutsou, John Matsoukas
Amino acid mutations to agonist peptide epitopes of myelin proteins have been used to modulate immune responses and experimental autoimmune encephalomyelitis (EAE, animal model of multiple sclerosis). Such amino acid alteration are termed, altered peptide ligands (APL). We have shown that the agonist myelin basic protein (MBP) 87-99 epitope (MBP87-99) with crucial T cell receptor (TCR) substitutions at positions 91 and 96 (K(91),P(96) (TCR contact residues) to R(91),A(96); [R(91),A(96)]MBP87-99) results in altered T cell responses and inhibits EAE symptoms...
November 19, 2016: Bioorganic & Medicinal Chemistry
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
#5
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/27906045/smoking-is-associated-with-the-concurrent-presence-of-multiple-autoantibodies-in-rheumatoid-arthritis-rather-than-with-anti-citrullinated-protein-antibodies-per-se-a-multicenter-cohort-study
#6
Tineke J van Wesemael, Sofia Ajeganova, Jennifer Humphreys, Chikashi Terao, Ammar Muhammad, Deborah P M Symmons, Alex J MacGregor, Ingiäld Hafström, Leendert A Trouw, Annette H M van der Helm-van Mil, Tom W J Huizinga, Tsuneyo Mimori, René E M Toes, Fumihiko Matsuda, Björn Svensson, Suzanne M M Verstappen, Diane van der Woude
BACKGROUND: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27896063/necrotizing-tracheobronchitis-associated-with-rheumatoid-arthritis
#7
Shigehisa Kajikawa, Kazushi Noda, Yasuhiro Nozaki
We report a case of necrotizing tracheobronchitis with rheumatoid arthritis. A 64 year-old-man presented with dry cough and was initially diagnosed with community-acquired pneumonia. The patient was admitted; he received initial antibiotic treatment. The treatment was effective and the symptoms worsened. Bronchoscopy was performed for more thorough examination. It showed that white and soft tissues were on the trachea-bronchus. Transbronchial biopsy of the tracheal lesions revealed necrotic tissue with squamous metaplasia and inflammatory cells...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/27895642/functional-and-structural-characterization-of-a-novel-hla-drb1-04-01-restricted-%C3%AE-enolase-t-cell-epitope-in-rheumatoid-arthritis
#8
Christina Gerstner, Anatoly Dubnovitsky, Charlotta Sandin, Genadiy Kozhukh, Hannes Uchtenhagen, Eddie A James, Johan Rönnelid, Anders Jimmy Ytterberg, Jennifer Pieper, Evan Reed, Carolina Tandre, Mary Rieck, Roman A Zubarev, Lars Rönnblom, Tatyana Sandalova, Jane H Buckner, Adnane Achour, Vivianne Malmström
Antibodies to citrullinated proteins, common in rheumatoid arthritis (RA) patients, are strongly associated to a specific set of HLA-DR alleles including HLA-DRB1*04:01, *04:04, and *01:01. Here, we first demonstrate that autoantibody levels toward the dominant citrullinated B cell epitope from α-enolase are significantly elevated in HLA-DRB1*04:01-positive RA patients. Furthermore, we identified α-enolase-derived T cell epitopes and demonstrated that native and citrullinated versions of several peptides bind with different affinities to HLA-DRB1*04:01, *04:04, and *01:01...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27895639/netosis-as-source-of-autoantigens-in-rheumatoid-arthritis
#9
REVIEW
Elisa Corsiero, Federico Pratesi, Edoardo Prediletto, Michele Bombardieri, Paola Migliorini
In neutrophils (but also in eosinophils and in mast cells), different inflammatory stimuli induce histone deimination, chromatin decondensation, and NET formation. These web-like structures that trap and kill microbes contain DNA, cationic granule proteins, and antimicrobial peptides, but the most abundant proteins are core histones. Histones contained in NETs have been deiminated, and arginines are converted in citrullines. While deimination is a physiological process amplified in inflammatory conditions, only individuals carrying genetic predisposition to develop rheumatoid arthritis (RA) make antibodies to deiminated proteins...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27891127/regulation-of-chemokine-activity-a-focus-on-the-role-of-dipeptidyl-peptidase-iv-cd26
#10
REVIEW
Mieke Metzemaekers, Jo Van Damme, Anneleen Mortier, Paul Proost
Chemokines are small, chemotactic proteins that play a crucial role in leukocyte migration and are, therefore, essential for proper functioning of the immune system. Chemokines exert their chemotactic effect by activation of chemokine receptors, which are G protein-coupled receptors (GPCRs), and interaction with glycosaminoglycans (GAGs). Furthermore, the exact chemokine function is modulated at the level of posttranslational modifications. Among the different types of posttranslational modifications that were found to occur in vitro and in vivo, i...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27887962/synthesis-of-a-biological-active-%C3%AE-hairpin-peptide-by-addition-of-two-structural-motifs
#11
Sabrina Fischer, Matthias Lamping, Maike Gold, Yvonne Röttger, Dörte Brödje, Richard Dodel, Renate Frantz, Mobarak Abu Mraheil, Trinad Chakraborty, Armin Geyer
The idea of privileged scaffolds - that there seem to be more bioactive compounds found around some structures than others - is well established for small drug molecules, but has little significance for standalone peptide secondary structures whose adaptable shapes escape the definition of a 3D motif in the absence of a protein scaffold. Here, we joined two independent biological functions in a single highly restricted peptide to support the hypothesis that the β-hairpin shape is the common basis of two otherwise unrelated biological recognition processes...
November 15, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27887639/prevalence-sensitivity-and-specificity-of-antibodies-against-carbamylated-proteins-in-a-monocentric-cohort-of-patients-with-rheumatoid-arthritis-and-other-autoimmune-rheumatic-diseases
#12
Arbi Pecani, Cristiano Alessandri, Francesca Romana Spinelli, Roberta Priori, Valeria Riccieri, Manuela Di Franco, Fulvia Ceccarelli, Tania Colasanti, Monica Pendolino, Riccardo Mancini, Simona Truglia, Cristiana Barbati, Marta Vomero, Danilo Sabatinelli, Francesca Morello, Guido Valesini, Fabrizio Conti
BACKGROUND: Antibodies against carbamylated proteins (anti-CarP) have been recently identified in the sera of patients with rheumatoid arthritis (RA). The objective of the study was to evaluate the prevalence, sensitivity and specificity of anti-CarP compared to anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF), replicating the existing data in a large cohort of Italian patients with RA and extending the evaluation to other autoimmune rheumatic diseases (AIRDs). METHODS: Serum samples (n = 607) from 309 patients with RA, 200 disease controls and 98 normal healthy subjects (NHS) were evaluated...
November 25, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27870649/the-reliability-of-disease-activity-score-in-28-joints-c-reactive-protein-might-be-overestimated-in-a-subgroup-of-rheumatoid-arthritis-patients-when-the-score-is-solely-based-on-subjective-parameters-a-cross-sectional-exploratory-study
#13
Inger Marie Jensen Hansen, Rikke Asmussen Andreasen, Mark Nam van Bui Hansen, Amir Emamifar
BACKGROUND: Disease Activity Score in 28 Joints (DAS28) is a scoring system to evaluate disease activity and treatment response in rheumatoid arthritis (RA). A DAS28 score of greater than 3.2 is a well-described limit for treatment intensification; however, the reliability of DAS28 might be overestimated. OBJECTIVE: The aim of this study was to evaluate the reliability of DAS28 in RA, especially focusing on a subgroup of patients with a DAS28 score of greater than 3...
November 19, 2016: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/27863807/head-to-head-comparison-of-certolizumab-pegol-versus-adalimumab-in-rheumatoid-arthritis-2-year-efficacy-and-safety-results-from-the-randomised-exxelerate-study
#14
Josef S Smolen, Gerd-Rüdiger Burmester, Bernard Combe, Jeffrey R Curtis, Stephen Hall, Boulos Haraoui, Ronald van Vollenhoven, Christopher Cioffi, Cécile Ecoffet, Leon Gervitz, Lucian Ionescu, Luke Peterson, Roy Fleischmann
BACKGROUND: To date, head-to-head trials comparing the efficacy and safety of biological disease-modifying antirheumatic drugs within the same class, including TNF inhibitors, in patients with active rheumatoid arthritis despite methotrexate therapy are lacking. We aimed to compare the efficacy and safety of two different TNF inhibitors and to assess the efficacy and safety of switching to the other TNF inhibitor without a washout period after insufficient primary response to the first TNF inhibitor at week 12...
November 11, 2016: Lancet
https://www.readbyqxmd.com/read/27863183/evidence-for-immune-relevance-of-prevotella-copri-a-gut-microbe-in-patients-with-rheumatoid-arthritis
#15
Annalisa Pianta, Sheila Arvikar, Klemen Strle, Elise E Drouin, Qi Wang, Catherine E Costello, Allen C Steere
OBJECTIVE: Prevotella copri, an intestinal microbe, may over-expand in stool samples of patients with new-onset rheumatoid arthritis (NORA), but it is not yet clear whether the organism has immune relevance in RA pathogenesis. METHODS: HLA-DR-presented peptides (T cell epitopes) from P. copri were sought directly from patients' synovial tissue or peripheral blood mononuclear cells (PBMC) using tandem mass spectrometry, followed by testing the antigenicity of peptides or their source proteins using samples from RA patients or comparison groups...
November 18, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27859022/igg1-and-igg4-anti-ccp-associate-with-shared-epitope-whereas-igg2-anti-ccp-associates-with-smoking-in-patients-with-recent-onset-rheumatoid-arthritis-the-swedish-tira-project
#16
Klara Martinsson, Anders Johansson, Alf Kastbom, Thomas Skogh
Given the possible importance of anti-citrullinated peptide/protein antibodies (ACPA) for initiation and progression of rheumatoid arthritis (RA), extended knowledge about the different isotypes and subclasses are important. In the present study we analysed the IgG subclasses regarding reactivity against citrullinated peptides (anti-CCP) among 504 clinically well-characterized patients with recent-onset RA in relation to smoking habits, shared epitope (SE) status, and IgA and pan IgG anti-CCP antibodies. All patients, regardless of pan IgG anti-CCP status, were analysed for IgG1-4 CCP reactivity...
November 17, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27855721/the-lung-microbiota-in-early-rheumatoid-arthritis-and-autoimmunity
#17
Jose U Scher, Vijay Joshua, Alejandro Artacho, Shahla Abdollahi-Roodsaz, Johan Öckinger, Susanna Kullberg, Magnus Sköld, Anders Eklund, Johan Grunewald, Jose C Clemente, Carles Ubeda, Leopoldo N Segal, Anca I Catrina
BACKGROUND: Airway abnormalities and lung tissue citrullination are found in both rheumatoid arthritis (RA) patients and individuals at-risk for disease development. This suggests the possibility that the lung could be a site of autoimmunity generation in RA, perhaps in response to microbiota changes. We therefore sought to test whether the RA lung microbiome contains distinct taxonomic features associated with local and/or systemic autoimmunity. METHODS: 16S rRNA gene high-throughput sequencing was utilized to compare the bacterial community composition of bronchoalveolar lavage fluid (BAL) in patients with early, disease-modifying anti-rheumatic drugs (DMARD)-naïve RA, patients with lung sarcoidosis, and healthy control subjects...
November 17, 2016: Microbiome
https://www.readbyqxmd.com/read/27852301/sleep-quality-in-chinese-patients-with-rheumatoid-arthritis-contributing-factors-and-effects-on-health-related-quality-of-life
#18
Genkai Guo, Ting Fu, Rulan Yin, Lijuan Zhang, Qiuxiang Zhang, Yunfei Xia, Liren Li, Zhifeng Gu
BACKGROUND: Poor sleep quality is common in rheumatoid arthritis (RA) patients and may lead to disease aggravation and decreased health-related quality of life (HRQoL). The increasing prevalence of poor sleep in RA patients is associated with adverse demographic, clinical, and psychological characteristics. However, there are currently no known reported studies related to the effects of sleep quality on HRQoL in RA patients from China. This cross-sectional study aims to evaluate the contributors of poor sleep and the effects of sleep quality on HRQoL in Chinese RA patients...
November 16, 2016: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/27848057/the-additional-benefit-of-ultrasonography-to-2010-acr-eular-classification-criteria-when-diagnosing-rheumatoid-arthritis-in-the-absence-of-anti-cyclic-citrullinated-peptide-antibodies
#19
Lanlan Ji, Xuerong Deng, Yan Geng, Zhibo Song, Zhuoli Zhang
The aim of this study was to assess the benefit of ultrasonography (US) contributing to 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria in diagnosing rheumatoid arthritis (RA), when anti-citrullinated protein (CCP) antibody and radiographic erosions are absent. Ninety-four patients suffering from arthritis of at least one joint in hands, symptom duration of less than 2 years, normal radiographs at baseline, and negative anti-CCP had 22 joint US assessments and were followed prospectively for at least 12 months...
November 15, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/27836419/ebv-infection-and-multiple-sclerosis-lessons-from-a-marmoset-model
#20
REVIEW
Bert A 'tHart, Yolanda S Kap, Elena Morandi, Jon D Laman, Bruno Gran
Multiple sclerosis (MS) is thought to be initiated by the interaction of genetic and environmental factors, eliciting an autoimmune attack on the central nervous system. Epstein-Barr virus (EBV) is the strongest infectious risk factor, but an explanation for the paradox between high infection prevalence and low MS incidence remains elusive. We discuss new data using marmosets with experimental autoimmune encephalomyelitis (EAE) - a valid primate model of MS. The findings may help to explain how a common infection can contribute to the pathogenesis of MS...
December 2016: Trends in Molecular Medicine
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