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Citrullination

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https://www.readbyqxmd.com/read/27933208/detection-of-antibodies-to-citrullinated-tenascin-c-in-patients-with-early-synovitis-is-associated-with-the-development-of-rheumatoid-arthritis
#1
Karim Raza, Anja Schwenzer, Maria Juarez, Patrick Venables, Andrew Filer, Chris D Buckley, Kim S Midwood
No abstract text is available yet for this article.
2016: RMD Open
https://www.readbyqxmd.com/read/27933065/current-challenges-and-limitations-in-antibody-based-detection-of-citrullinated-histones
#2
Indira Neeli, Marko Radic
Studies on NETosis demand reliable and convenient markers to monitor the progress of this form of cell death. Because a determining step in the release of nuclear chromatin NETs requires the conversion of arginine residues to citrulline residues in histones by peptidylarginine deiminase, citrullinated histones can provide such a marker. Here, we evaluate antibody reagents for the detection of citrulline residues in histones and observe alarming differences between commercial antisera and mouse and rabbit monoclonal antibodies in their ability to detect their nominal target residues...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27929094/peptidylarginine-deiminase-1-catalyzed-histone-citrullination-is-essential-for-early-embryo-development
#3
Xiaoqian Zhang, Xiaoqiu Liu, Mei Zhang, Tingting Li, Aaron Muth, Paul R Thompson, Scott A Coonrod, Xuesen Zhang
Peptidylarginine deiminase (PADI) enzymes are increasingly being associated with the regulation of chromatin structure and gene activity via histone citrullination. As one of the PADI family members, PADI1 has been mainly reported to be expressed in the epidermis and uterus, where the protein in keratinocytes is thought to promote differentiation by citrullinating filament proteins. However, the roles of PADI1 in preimplantation development have not been addressed. Using a PADI1-specific inhibitor and Padi1-morpholino knockdown, we found that citrullination of histone tails at H4R3 and H3R2/8/17 were markedly reduced in the 2- and 4-cell embryos...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27926664/absence-of-serological-rheumatoid-arthritis-biomarkers-in-inflammatory-bowel-disease-patients-with-arthropathies
#4
Sanne J H Van Erp, Marije K Verheul, E W Nivine Levarht, Johan J van der Reijden, Désirée van der Heijde, Floris A van Gaalen, Daniel W Hommes, Gary L Norman, Zakera Shums, Michael Mahler, Hein W Verspaget, Leendert A Trouw, Andrea E van der Meulen-de Jong
OBJECTIVE: Biomarkers that are associated with future progression to rheumatoid arthritis (RA) and joint destruction have been discovered previously in patients with arthralgia. The present study examined these RA biomarkers in inflammatory bowel disease (IBD) patients with arthropathies. PATIENTS AND METHODS: Sera from 155 IBD patients with and 99 IBD patients without arthropathies were analyzed for immunoglobulin (Ig) M rheumatoid factor (RF), IgA-RF, anti-cyclic citrullinated peptide 2, anti-cyclic citrullinated peptide 3...
December 6, 2016: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27923948/decreased-rate-of-plasma-arginine-appearance-in-murine-malaria-may-explain-hypoargininemia-in-children-with-cerebral-malaria
#5
Matthew S Alkaitis, Honghui Wang, Allison K Ikeda, Carol A Rowley, Ian J C MacCormick, Jessica H Chertow, Oliver Billker, Anthony F Suffredini, David J Roberts, Terrie E Taylor, Karl B Seydel, Hans C Ackerman
BACKGROUND:  Plasmodium infection depletes arginine, the substrate for nitric oxide synthesis, and impairs endothelium-dependent vasodilation. Increased conversion of arginine to ornithine by parasites or host arginase is a proposed mechanism of arginine depletion. METHODS:  We used high-performance liquid chromatography to measure plasma arginine, ornithine, and citrulline levels in Malawian children with cerebral malaria and in mice infected with Plasmodium berghei ANKA with or without the arginase gene...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27922857/comprehensive-assessment-of-the-arginine-pathway-and-its-relationship-to-inflammation-in-hiv
#6
Sahera Dirajlal-Fargo, S M Khurshid Alam, Abdus Sattar, Manjusha Kulkarni, Nicholas Funderburg, W H Wilson Tang, Grace A Mccomsey
BACKGROUND: Nitric oxide helps maintain vascular function and is generated through the oxidation of arginine. Whether altered arginine metabolism may lead to elevated levels of inflammation in HIV is unclear. METHODS: We performed a cross-sectional analysis of HIV-infected adults on stable ART with HIV-1 RNA < 50 copies/mL and HIV-uninfected controls. We measured biomarkers in the arginine pathway, markers of systemic inflammation, and monocyte activation. T-tests, chi-square tests and propensity score matching analyses were used to compare markers by HIV status, and multiple linear regressions were used to assess associations of arginine metabolites with markers of inflammation...
December 5, 2016: AIDS
https://www.readbyqxmd.com/read/27916980/the-immunopathogenesis-of-seropositive-rheumatoid-arthritis-from-triggering-to-targeting
#7
Vivianne Malmström, Anca I Catrina, Lars Klareskog
Patients with rheumatoid arthritis can be divided into two major subsets characterized by the presence versus absence of antibodies to citrullinated protein antigens (ACPAs) and of rheumatoid factor (RF). The antibody-positive subset of disease, also known as seropositive rheumatoid arthritis, constitutes approximately two-thirds of all cases of rheumatoid arthritis and generally has a more severe disease course. ACPAs and RF are often present in the blood long before any signs of joint inflammation, which suggests that the triggering of autoimmunity may occur at sites other than the joints (for example, in the lung)...
December 5, 2016: Nature Reviews. Immunology
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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/27890855/linker-stability-influences-the-anti-tumor-activity-of-acetazolamide-drug-conjugates-for-the-therapy-of-renal-cell-carcinoma
#18
Samuele Cazzamalli, Alberto Dal Corso, Dario Neri
Small molecule-drug conjugates (SMDCs) are increasingly being considered as an alternative to antibody-drug conjugates (ADCs) for the selective delivery of anticancer agents to the tumor site, sparing normal tissues. Carbonic anhydrase IX (CAIX) is a membrane-bound enzyme, which is over-expressed in the majority of renal cell carcinomas and which can be efficiently targeted in vivo, using charged derivatives of acetazolamide, a small heteroaromatic sulfonamide. Here, we show that SMDC products, obtained by the coupling of acetazolamide with monomethyl auristatin E (MMAE) using dipeptide linkers, display a potent anti-tumoral activity in mice bearing xenografted SKRC-52 renal cell carcinomas...
November 24, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27887962/synthesis-of-a-biological-active-%C3%AE-hairpin-peptide-by-addition-of-two-structural-motifs
#19
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
#20
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
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