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Homocitrullination or carbamylation

Cedric Delporte, Karim Zouaoui Boudjeltia, Paul G Furtmueller, Richard A Maki, Marc Dieu, Caroline Noyon, Monika Soudi, Damien Dufour, Catherine Coremans, Vincent Nuyens, Florence Reye, Alexandre Rousseau, Martine Raes, Nicole Moguilevsky, Michel Vanhaeverbeek, Jean Ducobu, Jean Neve, Bernard Robaye, Luc Vanhamme, Wanda F Reynolds, Christian Obinger, Pierre Van Antwerpen
Protein carbamylation by cyanate is a post-translational modification associated with several (patho)physiological conditions, including cardiovascular disorders. However, the biochemical pathways leading to protein carbamylation are incompletely characterized. This work demonstrates that the heme protein myeloperoxidase, which is secreted at high concentrations at inflammatory sites from stimulated neutrophils and monocytes, is able to catalyze the two-electron oxidation of cyanide to cyanate and promote the carbamylation of taurine, lysine and low-density-lipoproteins...
March 1, 2018: Journal of Biological Chemistry
Emma C de Moel, Veerle F A M Derksen, Gerrie Stoeken, Leendert A Trouw, Holger Bang, Robbert J Goekoop, Irene Speyer, Tom W J Huizinga, Cornelia F Allaart, René E M Toes, Diane van der Woude
BACKGROUND: The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. It is yet unknown whether this varying breadth of the autoantibody profile is associated with treatment outcomes. Therefore, we investigated whether the composition of the autoantibody profile in RA, as a marker of the underlying immunopathology, influences initial and long-term treatment outcomes. METHODS: In serum from 399 seropositive patients with RA in the IMPROVED study, drawn at baseline and at the moment of drug tapering, we measured IgG, IgM, and IgA isotypes for anti-cyclic citrullinated peptide-2 and anti-carbamylated protein antibodies, IgM and IgA rheumatoid factor, and reactivity against four citrullinated and two acetylated peptides (anti-modified protein antibodies (AMPAs))...
February 26, 2018: Arthritis Research & Therapy
Stéphane Jaisson, Christine Pietrement, Philippe Gillery
Protein carbamylation refers to a nonenzymatic modification, which consists in the binding of isocyanic acid on protein functional groups. This reaction is responsible for the alteration in structural and functional properties of proteins, which participate in their molecular aging. Protein molecular aging is now considered a molecular substratum for the development of chronic and inflammatory diseases, including atherosclerosis, chronic kidney disease, or rheumatoid arthritis. As a consequence, carbamylation-derived products have been proposed as interesting biomarkers in various pathological contexts and appropriate analytical methods have been developed for their quantification in biological fluids...
2018: Advances in Clinical Chemistry
Alicia Wong, Danuta Bryzek, Ewelina Dobosz, Carsten Scavenius, Pavel Svoboda, Maria Rapala-Kozik, Adam Lesner, Ivo Frydrych, Jan Enghild, Piotr Mydel, Jan Pohl, Paul R Thompson, Jan Potempa, Joanna Koziel
LL-37, the only human cathelicidin that is released during inflammation, is a potent regulator of immune responses by facilitating delivery of oligonucleotides to intracellular TLR-9, thereby enhancing the response of human plasmacytoid dendritic cells (pDCs) to extracellular DNA. Although important for pathogen recognition, this mechanism may facilitate development of autoimmune diseases. In this article, we show that citrullination of LL-37 by peptidyl-arginine deiminases (PADs) hindered peptide-dependent DNA uptake and sensing by pDCs...
February 23, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Juan-Manuel Anaya, Paula Restrepo-Jiménez, Carolina Ramírez-Santana
PURPOSE OF REVIEW: The autoimmune ecology refers to the interactions between individuals and their environment leading to a breakdown in immune tolerance and, therefore, to the development of one or more autoimmune diseases in such an individual. Herein, an update is offered on four specific factors associated with autoimmune diseases, namely, vitamin D, smoking, alcohol and coffee consumption from the perspective of exposome and metabolomics. RECENT FINDINGS: Smoking is associated with an increased risk for most of the autoimmune diseases...
February 12, 2018: Current Opinion in Rheumatology
Chihiro Kaneko, Tetsuo Kobayashi, Satoshi Ito, Noriko Sugita, Akira Murasawa, Kiyoshi Nakazono, Hiromasa Yoshie
OBJECTIVES: An interrelationship between rheumatoid arthritis (RA) and periodontitis has been suggested due to their common pathogenic mechanisms. Protein carbamylation and neutrophil extracellular traps (NETs) formation have been shown to be related to autoimmune conditions, including RA, but their association with periodontitis has not been elucidated. Therefore, we assessed whether or not circulating levels of carbamylated protein (CarP) and NETs are associated with periodontitis severity and influenced by periodontal treatment...
2018: PloS One
Mariana Hamer, Narella Bassi, Denise Agata Grela
Glycosylated hemoglobin (HbA1c) detection is performed routinely in hospitals as it is the most widespread confirmatory diagnosis of diabetes mellitus. Here we present a novel CE method for measuring HbA1c by introducing silica nanoparticles (NPs) modified with a boronic acid derivative (sugar loadings of 51 ± 2μg/mg) as pseudo-stationary phase. Before the sample injection, SiO2 NP-B(OH)2 were introduced via pressure. Electrophoretic separation was explored through variation of the buffer pH and separation voltage, being the best separation, resolution and shorter separation time achieved with a 25mM phosphate buffer pH 6...
January 31, 2018: Electrophoresis
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
Coralie Ruel, Marco Morani, Arnaud Bruneel, Christophe Junot, Myriam Taverna, François Fenaille, Nguyet Thuy Tran
ApolipoproteinC-III (ApoC-III) is a human plasma glycoprotein whose O-glycosylation can be altered as a result of congenital disorders of glycosylation (CDG). ApoC-III exhibits three major glycoforms whose relative quantification is of utmost importance for the diagnosis of CDG patients. Considering the very close structures of these glycoforms and their tendency to adsorb on the capillary, a thorough optimization of capillary electrophoresis (CE) parameters including preconditioning and in-between rinsing procedures was required to efficiently separate all the ApoC-III glycoforms...
January 12, 2018: Journal of Chromatography. A
Zhi-Jun Zhu, Lin Wei, Wei Qu, Li-Ying Sun, Ying Liu, Zhi-Gui Zeng, Liang Zhang, En-Hui He, Hai-Ming Zhang, Ji-Dong Jia, Zhong-Tao Zhang
We report a case of double domino liver transplantation in a 32-year-old woman who was diagnosed with familial amyloid polyneuropathy (FAP) and liver dysfunction. A two-stage surgical plan was designed, and one domino graft was implanted during each stage. During the first stage, an auxiliary domino liver transplantation was conducted using a domino graft from a 4-year-old female child with Wilson's disease. After removing the right lobe of the FAP patient's liver, the graft was rotated 90 degrees counterclockwise and placed along the right side of the inferior vena cava (IVC)...
November 28, 2017: World Journal of Gastroenterology: WJG
Barbara Hauser, Ulrike Harre
Many autoimmune diseases are associated with deranged bone metabolism. The resulting localized or systemic bone loss can compromise the quality of life of patients by causing local bone deformities or fragility fractures. There is emerging evidence that antibodies have a direct impact on key players of bone homeostasis, in particular osteoclasts. Clinical and pre-clinical studies provide insight into the function of autoantibodies related to Rheumatoid Arthritis (rheumatoid factor, anti-citrullinated protein antibodies, and anti-carbamylated protein antibodies) and their inflammation-independent interaction with bone cells...
December 4, 2017: Calcified Tissue International
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
Man Hon Yuen, Yu Hang Fong, Yap Shing Nim, Pak Ho Lau, Kam-Bo Wong
The ability of metallochaperones to allosterically regulate the binding/release of metal ions and to switch protein-binding partners along the metal delivery pathway is essential to the metallation of the metalloenzymes. Urease, catalyzing the hydrolysis of urea into ammonia and carbon dioxide, contains two nickel ions bound by a carbamylated lysine in its active site. Delivery of nickel ions for urease maturation is dependent on GTP hydrolysis and is assisted by four urease accessory proteins UreE, UreF, UreG, and UreH(UreD)...
December 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
M K Verheul, P A van Veelen, M A M van Delft, A de Ru, G M C Janssen, T Rispens, R E M Toes, L A Trouw
Carbamylation and citrullination are both post-translational modifications against which (auto)antibodies can be detected in sera of rheumatoid arthritis (RA) patients. Carbamylation is the chemical modification of a lysine into a homocitrulline, whereas citrullination is an enzymatic conversion of an arginine into a citrulline. It is difficult to distinguish between the two resulting amino acids due to similarities in structure. However, differentiation between citrulline and homocitrulline is important to understand the antigens that induce antibody production and to determine which modified antigens are present in target tissues...
February 2018: Autoimmunity Reviews
Patrick Lac, Maud Racapé, Lillian Barra, David A Bell, Ewa Cairns
OBJECTIVE: Antibodies that target citrullinated protein/peptide (ACPA) and homocitrullinated/carbamylated protein/peptide (AHCPA) are associated with rheumatoid arthritis (RA). The relationship between ACPA and AHCPA remains unclear. We examined the expression and cross-reactivity of these antibodies using citrulline- and homocitrulline-containing synthetic peptides, CitJED and HomoCitJED, respectively, which have equal numbers of citrulline or homocitrulline residues on the same peptide backbone...
March 2018: Journal of Rheumatology
Ralph Mösges, Christina Rohdenburg, Andrea Eichel, Gregor Zadoyan, Elena-Manja Kasche, Kija Shah-Hosseini, Walter Lehmacher, Petra Schmalz, Enrico Compalati
AIM: To determine the optimal effective and safe dose of sublingual immunotherapy tablets containing carbamylated monomeric allergoids in patients with grass pollen-induced allergic rhinoconjunctivitis. METHODS: In this prospective, randomized, double-blind, active-controlled, multicenter, Phase II study, four different daily doses were applied preseasonally for 12 weeks. RESULTS: Of 158 randomized adults, 155 subjects (safety population) received 300 units of allergy (UA)/day (n = 36), 600 UA/day (n = 43), 1000 UA/day (n = 39), or 2000 UA/day (n = 37)...
November 2017: Immunotherapy
Seong Sik Kang, Kyo-Cheol Mun, Ji Hae Seo, Misun Choe, Eunyoung Ha
Obesity is an important contributing factor to progression of chronic kidney disease. Cyanate, known as uremic toxin, is an electrophile produced spontaneously from urea or by myeloperoxidase-catalyzed oxidation of thiocyanate. Herein, we explored metabolic effects of cyanate in normal chow diet (NCD)- and high fat diet (HFD)-fed mice. Mice were treated with cyanate (1 mg/mL in drinking water) and fed NCD or HFD. Peritoneal glucose tolerance test (PGTT) and insulin tolerance test (ITT) were performed. Blood urea nitrogen (BUN) and creatinine concentrations were determined...
January 5, 2018: Chemico-biological Interactions
Cinzia Papadia, Sylwia Osowska, Luc Cynober, Alastair Forbes
The amino acid L-citrulline (CIT) is safely used from the neonatal period onwards in those with urea cycle defects and carbamyl phosphate synthetase or ornithine transcarbamylase deficiencies, but several lines of enquiry indicate that it might have a much wider therapeutic role. When protein intake is low and there is a catabolic state, endogenous arginine (ARG) synthesis cannot fully be met and its supplementation can prove challenging, particularly in patients with critical and multisystem illness. Supplementary CIT could constitute a safer but still focused means of delivering ARG to endothelial and immune cells as CIT is efficiently recycled into these cells and as kidneys can convert CIT into ARG...
October 16, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Sladjana Skopelja-Gardner, Jonathan D Jones, William F C Rigby
How and why we break tolerance to self-proteins still remains a largely unanswered question. Neutrophils have been identified as a rich source of autoantigens in a wide array of autoimmune diseases that arise as a consequence of different environmental and genetic factors, e.g. rheumatoid arthritis (RA), lupus, vasculitis, cystic fibrosis (CF) etc. Specifically, neutrophil extracellular trap (NET) formation has been identified as a link between innate and adaptive immune responses in autoimmunity. Autoantigens including neutrophil granular proteins (targeted by anti-neutrophil cytoplasmic antibodies, ANCA) as well as post-translationally modified proteins, i...
October 31, 2017: Journal of Autoimmunity
Marije K Verheul, Michel P M Vierboom, Bert A 't Hart, Rene E M Toes, Leendert A Trouw
BACKGROUND: Rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and anti-carbamylated protein (anti-CarP) antibodies are rheumatoid arthritis (RA)-associated autoantibodies. Besides their presence in human serum, anti-CarP antibodies have also been described in rodent models of arthritis, while ACPA are not consistently detectable. Data on these RA-associated autoantibodies in primates are not available. Therefore, we investigated the presence of RF, anti-CarP antibodies and ACPA in rhesus monkeys before and after collagen-induced arthritis immunizations...
November 2, 2017: Arthritis Research & Therapy
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