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Citrullinated peptides

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https://www.readbyqxmd.com/read/28650341/two-rheumatoid-arthritis-specific-autoantigens-correlate-microbial-immunity-with-autoimmune-responses-in-joints
#1
Annalisa Pianta, Sheila L Arvikar, Klemen Strle, Elise E Drouin, Qi Wang, Catherine E Costello, Allen C Steere
In rheumatoid arthritis (RA), immunological triggers at mucosal sites, such as the gut microbiota, may promote autoimmunity that affects joints. Here, we used discovery-based proteomics to detect HLA-DR-presented peptides in synovia or peripheral blood mononuclear cells and identified 2 autoantigens, N-acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA), as targets of T and B cell responses in 52% and 56% of RA patients, respectively. Both GNS and FLNA were highly expressed in synovia. GNS appeared to be citrullinated, and GNS antibody values correlated with anti-citrullinated protein antibody (ACPA) levels...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28649674/synovial-fibroblast-neutrophil-interactions-promote-pathogenic-adaptive-immunity-in-rheumatoid-arthritis
#2
Carmelo Carmona-Rivera, Philip M Carlucci, Erica Moore, Nithya Lingampalli, Hannes Uchtenhagen, Eddie James, Yudong Liu, Kevin L Bicker, Heidi Wahamaa, Victoria Hoffmann, Anca Irinel Catrina, PaulR Thompson, Jane H Buckner, William H Robinson, David A Fox, Mariana J Kaplan
Rheumatoid arthritis (RA) is characterized by synovial joint inflammation and by development of pathogenic humoral and cellular autoimmunity to citrullinated proteins. Neutrophil extracellular traps (NETs) are a source of citrullinated autoantigens and activate RA synovial fibroblasts (FLS), cells crucial in joint damage. We investigated the molecular mechanisms by which NETs promote proinflammatory phenotypes in FLS, and whether these interactions generate pathogenic anti-citrulline adaptive immune responses...
April 2017: Science Immunology
https://www.readbyqxmd.com/read/28647488/autoreactivity-to-malondialdehyde-modifications-in-rheumatoid-arthritis-is-linked-to-disease-activity-and-synovial-pathogenesis
#3
Caroline Grönwall, Khaled Amara, Uta Hardt, Akilan Krishnamurthy, Johanna Steen, Marianne Engström, Meng Sun, A Jimmy Ytterberg, Roman A Zubarev, Dagmar Scheel-Toellner, Jeffrey D Greenberg, Lars Klareskog, Anca I Catrina, Vivianne Malmström, Gregg J Silverman
Oxidation-associated malondialdehyde (MDA) modification of proteins can generate immunogenic neo-epitopes that are recognized by autoantibodies. In health, IgM antibodies to MDA-adducts are part of the natural antibody pool, while elevated levels of IgG anti-MDA antibodies are associated with inflammatory and autoimmune conditions. Yet, in human autoimmune disease IgG anti-MDA responses have not been well characterized and their potential contribution to disease pathogenesis is not known. Here, we investigate MDA-modifications and anti-MDA-modified protein autoreactivity in rheumatoid arthritis (RA)...
June 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28633586/porphyromonas-gingivalis-and-its-lps-differentially-regulate-the-expression-of-peptidyl-arginine-deiminases-in-human-chondrocytes
#4
René Elkaim, Isaac Maximiliano Bugueno-Valdebenito, Nadia Benkirane-Jessel, Henri Tenenbaum
Periodontitis, an inflammatory disease initiated by Gram-negative bacteria such as Porphyromonas gingivalis ( Pg), is considered as a risk factor for rheumatoid arthritis (RA). Our study aimed to determine the effect of Pg and its LPS on the expression of peptidyl arginine deiminase isotypes (PADs) in human primary chondrocytes (HC). HCs were infected with Pg and activated by its LPS (LPS- Pg). The mRNA expression levels of human PADs (1, 2, 3, 4 and 6) and bacterial enzyme (PADPg) were quantified by RT-qPCR...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28629188/serum-biomarkers-for-discrimination-between-hepatitis-c-related-arthropathy-and-early-rheumatoid-arthritis
#5
Isabela Siloşi, Lidia Boldeanu, Viorel Biciuşcă, Maria Bogdan, Carmen Avramescu, Citto Taisescu, Vlad Padureanu, Mihail Virgil Boldeanu, Anica Dricu, Cristian Adrian Siloşi
In the present study, we aimed to estimate the concentrations of cytokines (interleukin 6, IL-6, tumor necrosis factor-α, TNF-α) and auto-antibodies (rheumatoid factor IgM isotype, IgM-RF, antinuclear auto-antibodies, ANA, anti-cyclic citrullinated peptide antibodies IgG isotype, IgG anti-CCP3.1, anti-cardiolipin IgG isotype, IgG anti-aCL) in serum of patients with eRA (early rheumatoid arthritis) and HCVrA (hepatitis C virus-related arthropathy) and to assess the utility of IL-6, TNF-α together with IgG anti-CCP and IgM-RF in distinguishing between patients with true eRA and HCVrA, in the idea of using them as differential immunomarkers...
June 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28627096/high-titer-of-anti-citrullinated-peptide-antibody-is-a-risk-factor-for-severe-carotid-atherosclerotic-plaque-in-patients-with-rheumatoid-arthritis-the-tomorrow-study
#6
Tadashi Okano, Kentaro Inui, Yuko Sugioka, Kenichi Sugioka, Yoshiki Matsumura, Shinji Takahashi, Masahiro Tada, Kenji Mamoto, Shigeyuki Wakitani, Tatsuya Koike, Hiroaki Nakamura
AIM: Cardiovascular disease is one of the complications of rheumatoid arthritis (RA). We researched the morbidity and severity of existing carotid atherosclerosis plaque and associated risk factors in patients with RA. METHOD: This study included 413 participants, including 208 patients with RA and 205 age- and sex-matched healthy volunteers. Carotid ultrasound, clinical data collection and assessment of cardiovascular risk factors were performed. Atherosclerotic plaque was defined as an intima-media thickness ≥ 1...
June 19, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28619044/differing-specificities-and-isotypes-of-anti-citrullinated-peptide-protein-antibodies-in-palindromic-rheumatism-and-rheumatoid-arthritis
#7
Sonia Cabrera-Villalba, María José Gomara, Juan D Cañete, Julio Ramírez, Georgina Salvador, Virginia Ruiz-Esquide, Maria Victoria Hernández, José Inciarte-Mundo, Isabel Haro, Raimon Sanmartí
BACKGROUND: To analyze differences in the recognition of anti-citrullinated peptide/protein antibody (ACPA) citrullinated epitopes and isotypes in patients with palindromic rheumatism (PR) and rheumatoid arthritis (RA). METHODS: ACPA fine specificities (citrullinated peptides of enolase, fibrin, and vimentin) and isotypes (IgG, IgM, and IgA) were analyzed in 54 patients with longstanding PR and 54 patients with established RA. RESULTS: CCP2 tested positive in 66...
June 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28611162/a-large-chronic-pericardial-effusion-in-an-ultramarathon-runner-with-anti-ccp-positive-rheumatoid-arthritis
#8
Thomas J McClelland, Rose Penfold, Stefan Kluzek, Navraj S Nagra
Pericardial effusions arise as an extra-articular manifestation of rheumatoid arthritis (RA). Pericardial effusions are often asymptomatic, particularly in the early phase, but patients are at risk of cardiac tamponade as the effusion progresses. We discuss the case of a 40-year-old male ultramarathon runner with RA who presented with mild pleuritic chest pain and exertional dyspnoea after a recent long-haul flight. Despite a relative tachycardia, his observations were otherwise unremarkable. His blood tests revealed a C-reactive protein (CRP) of 86 mg/L and an anti-cyclic citrullinated peptide (anti-CCP) titre of 360 units/mL...
June 13, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28600350/rheumatoid-arthritis-and-polymyalgia-rheumatica-occurring-after-immune-checkpoint-inhibitor-treatment
#9
Rakiba Belkhir, Sébastien Le Burel, Laetitia Dunogeant, Aurélien Marabelle, Antoine Hollebecque, Benjamin Besse, Alexandra Leary, Anne-Laure Voisin, Clémence Pontoizeau, Laetitia Coutte, Edouard Pertuiset, Gaël Mouterde, Olivier Fain, Olivier Lambotte, Xavier Mariette
OBJECTIVES: Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 (PD-1) have demonstrated improved survival for multiple cancers. However, these new drug classes have led to increased immune-related adverse events (IrAE). Rheumatic IrAEs have not been well described in clinical trials. We report here cases of rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) occurring after ICI treatment. METHODS: This was a retrospective study of patients receiving an ICI in whom symptoms of arthritis or arthralgia developed and revealed a diagnosis of RA or PMR...
June 9, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28592428/ebv-infection-empowers-human-b-cells-for-autoimmunity-role-of-autophagy-and-relevance-to-multiple-sclerosis
#10
Elena Morandi, S Anwar Jagessar, Bert A 't Hart, Bruno Gran
The efficacy of B cell depletion therapy in multiple sclerosis indicates their central pathogenic role in disease pathogenesis. The B lymphotropic EBV is a major risk factor in multiple sclerosis, via as yet unclear mechanisms. We reported in a nonhuman primate experimental autoimmune encephalomyelitis model that an EBV-related lymphocryptovirus enables B cells to protect a proteolysis-sensitive immunodominant myelin oligodendrocyte glycoprotein (MOG) epitope (residues 40-48) against destructive processing...
June 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28592052/-the-457th-case-polyarthralgia-back-pain-and-subcutaneous-masses
#11
M Li, D Wu, W J Zheng, M T Li, X F Zeng
A 54-year-old man was admitted to the Department of Rheumatology in Peking Union Medical College Hospital due to polyarthritis, back pain and multiple subcutaneous masses. He had symmetrical polyarthritis at onset, which was diagnosed as rheumatoid arthritis. His follow-up and treatment were irregular. Back pain and multiple subcutaneous masses developed 2 year ago. Erythrocyte sedimentation rate and C-reactive protein were elevated. Rheumatoid factor and Anti-cyclic citrullinated peptide antibody were positive...
June 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28589668/strongly-positive-anti-ccp-antibodies-in-patients-with-sacroiliitis-or-reactive-arthritis-post-e-%C3%A2-coli-infection-a-mini-case-series-based-review
#12
Miljyot Singh Sangha, Matthew Liam Wright, Coziana Ciurtin
We report here on four cases of patients with strongly positive anti-citrullinated cyclic peptides (anti-CCP) antibodies and clinical features of seronegative spondyloarthritis (SpA) and reactive arthritis. The four patients had various clinical presentations: one had an initial diagnosis of seropositive rheumatoid arthritis (RA) with involvement of the sacroiliac joints (similar to previous reports of the association of two diseases); one had a clinical picture of reactive arthritis following an episode of an Escherichia coli positive urinary tract infection; and two had asymmetrical sacroiliitis (SII), but no evidence of peripheral joint involvement (never reported before)...
June 6, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28581157/novel-furan-containing-peptide-based-inhibitors-of-protein-arginine-deiminase-type-iv-pad4
#13
Chian Ying Teo, Bimo A Tejo, Adam Thean Chor Leow, Abu Bakar Salleh, Mohd Basyaruddin Abdul Rahman
Protein arginine deiminase type IV (PAD4) is responsible for the post-translational conversion of peptidylarginine to peptidylcitrulline. Citrullinated protein is the autoantigen in rheumatoid arthritis, and therefore, PAD4 is currently a promising therapeutic target for the disease. Recently, we reported the importance of the furan ring in the structure of PAD4 inhibitors. In this study, the furan ring was incorporated into peptides to act as the "warhead" of the inhibitors for PAD4. IC50 studies showed that the furan-containing peptide-based inhibitors were able to inhibit PAD4 to a better extent than the furan-containing small molecules that were previously reported...
June 5, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28578645/the-anti-migraine-effects-of-m2000-%C3%AE-d-mannuronic-acid-on-a-patient-with-rheumatoid-arthritis-as-a-case-report
#14
Mahdi Vojdanian, Hossein Ahmadi, Ahmad Reza Jamshidi, Mahdi Mahmoudi, Farhad Gharibdoost, Anis Barati, Abbas Mirshafiey
BACKGROUND: Rheumatoid arthritis (RA) and migraine are both common disorders which are caused by a faulty immune system and autonomic nervous system dysfunction, respectively. Although current treatment outlook has been shown a great improvement in these two diseases, however many side effects have been reported. CASE REPORT: We report a case of 43-years-female that has been suffered from rheumatoid arthritis for 3 years with a 6 years history of migraine. She had used different types of medication for both rheumatoid arthritis and migraine but during these 6 years no improvement was observed and even migraine progression in this patient became worse...
June 4, 2017: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/28578492/anti-citrullinated-protein-antibodies-in-the-diagnosis-of-rheumatoid-arthritis-ra-diagnostic-performance-of-automated-anti-ccp-2-and-anti-ccp-3-antibodies-assays
#15
Ine Vos, Christof Van Mol, Leendert A Trouw, Michael Mahler, Jaap A Bakker, Jan Van Offel, Luc De Clerck, Tom W Huizinga
This study compares the diagnostic performance of a second generation anti-cyclic citrullinated peptide antibody (CCP2) with a third generation anti-CCP antibodies assay (CCP3), as well as the combination of both tests. Serum samples of 127 patients were analyzed. IgG anti-CCP 2 and IgM rheumatoid factor were determined by EliA™ technique on a Phadia 250 instrument (Thermo Fisher Scientific), anti-CCP3 by the Quanta Flash™ anti-CCP3 IgG kit, BIO-FLASH Rapid Response Chemiluminscence Analyzer (INOVA Diagnostics)...
July 2017: Clinical Rheumatology
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
#16
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/28556615/characteristics-of-germinal-center-like-structures-in-patients-with-sj%C3%A3-gren-s-syndrome
#17
Jing He, Yuebo Jin, Xia Zhang, Yunshan Zhou, Ru Li, Yijun Dai, Xiaolin Sun, Jingzhong Zhao, Jianping Guo, Zhanguo Li
AIM: To analyze the relationship between ectopic germinal centers (GCs) in the salivary glands and the clinical/laboratory characteristics of patients with Sjögren's syndrome (SS). METHODS: Retrospectively, 126 patients with primary SS (pSS) and 16 patients with secondary SS (sSS) were analyzed. Minor salivary gland biopsies were evaluated for the presence of GC-like morphology by hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining for CD21. Clinical and serological data were obtained from medical records...
February 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28551357/padi4-polymorphisms-and-the-functional-haplotype-are-associated-with-increased-rheumatoid-arthritis-susceptibility-a-replication-study-in-a-southern-mexican-population
#18
Christian Johana Baños-Hernández, José Eduardo Navarro-Zarza, Isela Parra-Rojas, Mirna Vázquez-Villamar, Jorge Ramón Padilla-Gutiérrez, Yeminia Valle, Zyanya Reyes-Castillo, Nora Magdalena Torres-Carrillo, Samuel García-Arellano, Lorena Michele Brennan-Bourdon, José Francisco Muñoz-Valle
Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The peptidyl arginine deiminase type IV (PADI4) gene has been associated with RA susceptibility in several populations. We addressed the relationship between three exonic PADI4 gene single nucleotide polymorphisms (SNPs) PADI4_89 (rs11203366), PADI4_90 (rs11203367) and PADI4_92 (rs874881) and related haplotypes with RA in a population from Southern México. This study included 200 RA patients and 200 control subjects...
May 25, 2017: Human Immunology
https://www.readbyqxmd.com/read/28536076/polyarginine-and-its-analogues-inhibit-p53-mutant-aggregation-and-cancer-cell-proliferation-in%C3%A2-vitro
#19
Zhaolin Chen, Jun Chen, Venkateshwar G Keshamouni, Mathumai Kanapathipillai
Arginine, a cationic amino acid is known to stabilize proteins under harsh conditions. It is widely used to stabilize protein aggregation, and to correct protein folding during protein production. Hence it would be a good therapeutic candidate for treating protein aggregation related diseases. Recent reports suggest, that the aggregation of tumor suppressor protein p53 is one of the leading causes of tumor progression. When mutated, p53 protein aggregates, loses its function leading to unwanted cell growth and ultimately results in tumor...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28535888/independence-of-carbohydrate-deficient-isoforms-of-transferrin-and-cyclic-citrullinated-peptides-in-rheumatoid-arthritis
#20
Monika Gudowska, Ewa Gindzienska-Sieskiewicz, Ewa Gruszewska, Bogdan Cylwik, Stanislaw Sierakowski, Maciej Szmitkowski, Lech Chrostek
OBJECTIVE: The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and citrullination by means of autoantibodies to cyclic citrullinated peptides. METHODS: The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti-CCP were measured using the chemiluminescent method and rheumatoid factor by immunoturbidimetric method...
May 2017: Revista Brasileira de Reumatologia
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