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Citrullinated peptides

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https://www.readbyqxmd.com/read/29338885/concurrence-of-rheumatoid-arthritis-and-calcium-pyrophosphate-deposition-disease-a-case-collection-and-review-of-the-literature
#1
Viktoriya Sabchyshyn, Irina Konon, Lawrence M Ryan, Ann K Rosenthal
OBJECTIVE: Calcium pyrophosphate deposition disease (CPDD) is arthritis caused by calcium pyrophosphate (CPP) crystal deposition in joints. It is commonly associated with aging as well as a handful of metabolic syndromes. Recent epidemiologic studies suggest a positive association of CPDD and rheumatoid arthritis (RA). Yet how these diseases are related remains unclear. We set out to describe 21 well-characterized patients with both diagnoses. METHODS: Medical records of patients with both RA and CPDD identified at a single academic practice site were reviewed for age, gender, age of CPDD and RA onset, disease duration, joint involvement, and lab values including rheumatoid factor (RF), cyclic citrullinated peptide antibody (CCP), iron studies, and parathyroid hormone and calcium levels...
December 2, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29337196/nicorandil-and-theophylline-can-protect-experimental-rats-against-complete-freund-s-adjuvant-induced-rheumatoid-arthritis-through-modulation-of-jak-stat-rankl-signaling-pathway
#2
Ahmed Gaafar Ahmed Gaafar, Basim Anwar Shehata Messiha, Ahmed Mohamed Labib Abdelkafy
Signaling pathways are interesting fields of study of pathogenesis and treatment trials. We elucidated the possible protective effects of nicorandil (15mg/kg/day) and theophylline (20mg/kg/day) on experimentally-induced RA, focusing on the role of JAK (Janus Kinase) / STAT (Signal Transducer and Activator of Transcription) / RANKL (Receptor Activator of Nuclear factor-Kappa B Ligand) / cytokine signaling pathway. Four sets of experiments were performed. First, effect of test agents on normal animals was evaluated...
January 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29336646/anti-cyclic-citrullinated-peptide-antibodies-other-common-autoantibodies-and-smoking-as-risk-factors-for-lymphoma-in-patients-with-rheumatoid-arthritis
#3
E Baecklund, C Backlin, J Rönnelid, R Toes, Twj Huizinga, E Åhlin, J Askling, F H Hochberg, L Klareskog, J Kay, K E Smedby
OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma. There is no biomarker to indicate future lymphoma risk in RA and it is not known whether factors associated with an increased risk of RA also confer an increased risk of lymphoma. We investigated whether anti-cyclic citrullinated peptide (CCP) antibodies, other autoantibodies, and smoking, are associated with lymphoma development in RA. METHOD: From two population-based case-control studies, the Scandinavian Lymphoma Etiology (SCALE) study and the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) I study, we identified lymphoma cases with a validated RA diagnosis (n = 50), to whom we matched study participants with RA but no lymphoma (n = 261), lymphoma but no RA (n = 257), and neither RA nor lymphoma (n = 233)...
January 16, 2018: Scandinavian Journal of Rheumatology
https://www.readbyqxmd.com/read/29336618/rheumatoid-arthritis-a-single-center-egyptian-experience
#4
B R Sakr, M M Elfishawi, M H ElArousy, A K Hatw, A N AbdulKarim, A B Tammam, A N Kotp, M E Hamed, I E Genedy, E D El Desouky, Z O Nawito
OBJECTIVE: Demonstration of rheumatoid arthritis (RA) characteristics in a large cohort of Egyptian patients. METHODS: Retrospective analysis of data of 3219 RA patients attending the Rheumatology outpatient clinic, Kasr Alainy Hospital, Cairo University; from January 1995 till December 2015. RESULTS: Mean age at disease onset was 36.1 ±13.4 years; 2774 (84%) were females and mean disease duration was 12.9 ±7.9 years. Regarding number of joint affected at disease onset; polyarticular pattern was found in 77...
January 16, 2018: Immunological Investigations
https://www.readbyqxmd.com/read/29336365/il1f7-gene-polymorphism-is-not-associated-with-rheumatoid-arthritis-susceptibility-in-the-northern-chinese-han-population-a-case-control-study
#5
Xiao-Ying Zhang, Yu Zuo, Chun Li, Xin Tu, Hu-Ji Xu, Jian-Ping Guo, Zhan-Guo Li, Rong Mu
BACKGROUND: Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene polymorphism in RA susceptibility in a large cohort of patients. METHODS: Five selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population...
January 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29335340/anticitrullinated-protein-antibodies-induce-inflammatory-gene-expression-profile-in-peripheral-blood-cells-from-ccp-positive-patients-with-ra
#6
Smadar Gertel, Gidi Karmon, Eszter Szarka, Ora Shovman, Esther Houri-Levi, Edna Mozes, Yehuda Shoenfeld, Howard Amital
OBJECTIVE: Anticitrullinated protein antibodies (ACPA) have major diagnostic significance in rheumatoid arthritis (RA). ACPA are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. The presence of ACPA is associated with joint damage and extraarticular manifestations, suggesting that ACPA may have a significant role in the pathogenesis of RA. METHODS: To verify the effect of ACPA on RA-immune cells, peripheral blood mononuclear cells (PBMC) from cyclic citrullinated peptide (CCP)-positive patients with RA and healthy controls were cocultured in vitro with ACPA...
January 15, 2018: Journal of Rheumatology
https://www.readbyqxmd.com/read/29330273/rheumatoid-disease-an-unusual-cause-of-relapsing-meningoencephalitis
#7
Sian K Alexander, Maria Di Cicco, Ute Pohl, Alberto Cifelli
A 73-year-old man presented with three episodes of dysphasia and disinhibited behaviour, a single seizure and transient ischaemic attack-like events characterised by right arm and/or leg weakness. These episodes were separated by month-long asymptomatic intervals. Medical history included rheumatoid arthritis, which was clinically quiescent on leflunomide.Repeated cerebrospinal fluid examination showed a persistent lymphocytosis with mildly reduced glucose and elevated protein; oligoclonal bands and viral PCR were negative...
January 12, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29317506/the-interplay-between-citrullination-and-hla-drb1-polymorphism-in-shaping-peptide-binding-hierarchies-in-rheumatoid-arthritis
#8
Yi Tian Ting, Jan Petersen, Sri H Ramarathinam, Stephen W Scally, Khai L Loh, Ranjeny Thomas, Anish Suri, Daniel G Baker, Anthony W Purcell, Hugh H Reid, Jamie Rossjohn
The HLA-DRB1 locus is strongly associated with rheumatoid arthritis (RA) susceptibility, whereupon citrullinated self-peptides bind to HLA-DR molecules bearing the shared epitope (SE) amino acid motif.  However, the differing propensity for citrullinated/non-citrullinated self-peptides to bind given HLA-DR allomorphs remains unclear.  Here, we used a fluorescence polarisation assay to determine a hierarchy of binding affinities of 34 self-peptides implicated in RA against three HLA-DRB1 allomorphs (HLA-DRB1*04:01/*04:04/*04:05) each possessing the SE motif...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29314830/x-ray-structures-of-the-proprotein-convertase-furin-bound-with-substrate-analog-inhibitors-reveal-substrate-specificity-determinants-beyond-the-s4-pocket
#9
Sven O Dahms, Kornelia Hardes, Torsten Steinmetzer, Manuel E Than
The proprotein convertase (PC) furin is a highly specific serine protease modifying and thereby activating proteins in the secretory pathway by proteolytic cleavage. Its substrates are involved in many diseases including cancer and infections caused by bacteria and viruses. Understanding furin's substrate specificity is of crucial importance for the development of pharmacologically applicable inhibitors. Using protein X-ray crystallography we investigated the extended substrate binding site of furin in complex with three peptide derived inhibitors at up to 1...
January 9, 2018: Biochemistry
https://www.readbyqxmd.com/read/29308319/citrullinated-%C3%AE-enolase-is-an-effective-target-for-anti-cancer-immunity
#10
Katherine Cook, Ian Daniels, Peter Symonds, Tracy Pitt, Mohamed Gijon, Wei Xue, Rachael Metheringham, Lindy Durrant, Victoria Brentville
Targeting post-translationally modified epitopes may provide a new strategy for generating tumor specific immune responses. Citrullination is the post-translational modification of arginine to citrulline catalyzed by peptidylarginine deaminase (PAD) enzymes. Presentation of citrullinated peptides on MHC-II has been associated with autophagy. Tumors upregulate autophagy and present citrullinated peptides in response to stresses including nutrient deprivation, oxygen deprivation, redox stress and DNA damage, making them good targets for immune attack...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308281/case-series-monoarticular-rheumatoid-arthritis
#11
Jeffrey Sarazin, Elena Schiopu, Rajaie Namas
Objective: Monoarticular presentation of rheumatoid arthritis is infrequent and has been previously reported to involve large joints such as the hip and knee joints. Here we report a case series of four patients presenting to the University of Michigan in 2015 with monoarticular rheumatoid arthritis, one with small and three with large joint involvement. Material and Methods: In total, four patients with monoarticular rheumatoid arthritis were treated in the Division of Rheumatology, University of Michigan...
December 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/29290168/the-economic-burden-of-acpa-positive-status-among-patients-with-rheumatoid-arthritis
#12
Jason Shafrin, Mahlet Gizaw Tebeka, Kwanza Price, Chad Patel, Kaleb Michaud
BACKGROUND: Anticitrullinated protein antibodies (ACPAs) are serological biomarkers associated with early, rapidly progressing rheumatoid arthritis (RA), including more severe disease and joint damage. ACPA testing has become a routine tool for RA diagnosis and prognosis. Furthermore, treatment efficacy has been shown to vary by ACPA-positive status. However, it is not clear if the economic burden of patients with RA varies by ACPA status. OBJECTIVE: To determine if the economic burden of RA varies by patient ACPA status...
January 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29287593/upregulation-of-citrullination-pathway-from-autoimmune-to-idiopathic-lung-fibrosis
#13
Katerina D Samara, Athina Trachalaki, Eliza Tsitoura, Anastasios V Koutsopoulos, Eleni D Lagoudaki, Ismini Lasithiotaki, George Margaritopoulos, Panagiotis Pantelidis, Eleni Bibaki, Nikolaos M Siafakas, Nikolaos Tzanakis, Athol U Wells, Katerina M Antoniou
BACKGROUND: Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity. Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis remains unclear...
December 29, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29273071/profiling-micrornas-in-individuals-at-risk-of-progression-to-rheumatoid-arthritis
#14
L Ouboussad, L Hunt, E M A Hensor, J L Nam, N A Barnes, P Emery, M F McDermott, M H Buch
BACKGROUND: Individuals at risk of rheumatoid arthritis (RA) demonstrate systemic autoimmunity in the form of anti-citrullinated peptide antibodies (ACPA). MicroRNAs (miRNAs) are implicated in established RA. This study aimed to (1) compare miRNA expression between healthy individuals and those at risk of and those that develop RA, (2) evaluate the change in expression of miRNA from "at-risk" to early RA and (3) explore whether these miRNAs could inform a signature predictive of progression from "at-risk" to RA...
December 22, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29259607/associations-between-viral-infection-history-symptoms-granulocyte-reactive-oxygen-species-activity-and-active-rheumatoid-arthritis-disease-in-untreated-women-at-onset-results-from-a-longitudinal-cohort-study-of-tatarstan-women
#15
Marina I Arleevskaya, Albina Z Shafigullina, Yulia V Filina, Julie Lemerle, Yves Renaudineau
To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29242008/immune-responses-to-peptides-containing-homocitrulline-or-citrulline-in-the-dr4-transgenic-mouse-model-of-rheumatoid-arthritis
#16
Patrick Lac, Sheri Saunders, Elena Tutunea-Fatan, Lillian Barra, David A Bell, Ewa Cairns
Antibodies to proteins/peptides containing citrulline are hallmarks of Rheumatoid Arthritis (RA). These antibodies are strongly associated with the expression of the Shared Epitope (SE). RA patients also generate antibodies to homocitrulline-containing proteins/peptides (also referred to as anti-carbamylated protein antibodies (Anti-CarP)). This study was undertaken to investigate the relationship between homocitrulline and citrulline immune responses using an established mouse model of RA: DR4-transgenic (DR4tg) mice that express the human SE...
December 11, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29237149/association-of-antibodies-to-citrullinated-protein-antigens-with-blood-pressure-in-first-degree-relatives-of-rheumatoid-arthritis-patients-the-studies-of-the-etiology-of-rheumatoid-arthritis
#17
Jan M Hughes-Austin, Ryan W Gan, Kevin D Deane, Michael H Weisman, M Kristen Demoruelle, Jeremy Sokolove, William H Robinson, V Michael Holers, Jill M Norris, Joachim H Ix
BACKGROUND: Hypertension is more common in patients with rheumatoid arthritis (RA) than in the general population. It is unknown whether hypertension is due to RA-related medications or the disease itself. Therefore, we sought to investigate associations between RA-related autoantibodies, specifically antibodies to citrullinated protein antigens (ACPA) and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in first-degree relatives of RA patients, who were free of RA and RA-related medications...
December 13, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/29227683/discovery-of-peptidomimetic-antibody-drug-conjugate-linkers-with-enhanced-protease-specificity
#18
Binqing Wei, Janet Gunzner-Toste, Hui Yao, Tao Wang, Jing Wang, Zijin Xu, Jinhua Chen, John Wai, Jim Nonomiya, Siao Ping Tsai, Josefa Dela Cruz-Chuh, Katherine Ruth Kozak, Yichin Liu, Shang-Fan Yu, Jeff Lau, Guangmin Li, Gail D Lewis Phillips, Doug Leipold, Amrita Kamath, Dian Su, Keyang Xu, Charles Eigenbrot, Stefan Steinbacher, Rachana Ohri, Helga Raab, Leanna R Staben, Guiling Zhao, John A Flygare, Thomas H Pillow, Vishal Verma, Brian Salvatore Safina
Antibody-Drug Conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite the progress, improvements in ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases have shown sufficient stability in serum, and effective payload-release in targeted cells. If the linker can be preferentially hydrolyzed by tumor-specific proteases, safety margin may improve. However, the use of peptide-based linkers limits our ability to modulate protease specificity...
December 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29221127/long-noncoding-rnas-expression-profile-and-functional-networks-in-rheumatoid-arthritis
#19
Donghua Xu, Ye Jiang, Lu Yang, Xixing Hou, Jihong Wang, Weijun Gu, Xiaodong Wang, Lanyu Liu, Juan Zhang, Hongying Lu
The modifying effects of long noncoding RNAs (lncRNAs) in rheumatoid arthritis (RA) recently have drawn much attention; however, the underlying mechanisms remain largely unknown. Herein, we aim to investigate the expression profile of lncRNAs in RA and identify promising targets for RA diagnosis and treatment. Microarray screening and real-time PCR of lncRNAs were performed by use of serum samples from 3 RA patients and 3 healthy controls. Significantly differentially expressed lncRNAs were verified in serum samples from 43 RA patients and 40 healthy controls by real-time PCR...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29204430/carbamylation-citrullination-of-igg-fc-in-bronchiectasis-established-ra-with-bronchiectasis-and-ra-smokers-a-potential-risk-factor-for-disease
#20
David Hutchinson, Alexander Clarke, Kate Heesom, Daniel Murphy, Paul Eggleton
Bronchiectasis (BR) and smoking are risk factors for rheumatoid arthritis (RA) development. The mechanisms by which smoking and BR trigger RA are unknown, but are associated with concurrent rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) positivity. Anti-carbamylated protein antibodies (anti-CarP) have also been observed in BR patients and can be induced by smoking. Given that RF only has one antigen, immunoglobulin G (IgG) we have suggested that post-translational modifications to the Fc region of the heavy chain of IgG (IgGH) are a potential explanation for the clustering of the RA-associated autoantibodies in RA...
July 2017: ERJ Open Research
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