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Citrullinated peptides

A L Fedele, L Petricca, B Tolusso, S Alivernini, S Canestri, C Di Mario, S L Bosello, G Ferraccioli, E Gremese
OBJECTIVES: To define baseline clinical and immunological characteristics [anti-citrullinated peptide antibodies (ACPAs), immunoglobulin M (IgM)- and IgA-rheumatoid factor (RF), and interleukin-6 (IL-6) levels] involved in determining baseline erosiveness, outcome, and radiographic progression among seropositive and seronegative early rheumatoid arthritis (ERA) patients. METHOD: The 408 ERA patients enrolled in the study were monitored every 3 months according to the treat-to-target strategy...
March 15, 2018: Scandinavian Journal of Rheumatology
Lazaros I Sakkas, Dimitrios P Bogdanos
PURPOSE OF REVIEW: This review highlights the most recent data obtained in this field and provides clues toward the better understanding of the close interplay between microbiota and host, leading to autoimmune diseases. RECENT FINDINGS: A well-described model of microbiota/host interaction of relevance to autoimmunity is that linking anti-citrullinated peptide antibody positive rheumatoid arthritis and alterations of microbiota largely concentrating on Porphyromonas gingivalis and more recently of Aggregatibacter actinomycetemcomitans and Prevotella copri...
March 13, 2018: Current Opinion in Rheumatology
Ismet H Bajraktari, Blerim Krasniqi, Sylejman Rexhepi, Sadi Bexheti, Elton Bahtiri, Halit Bajraktari, Besim Luri
BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterised by intra-articular and extra-articular manifestations but very rarely with coxitis. AIM: This study aimed to investigate the prevalence of coxitis, clinical changes, and its correlation with the parameters of inflammatory activity. METHODS: A cohort of 951 patients diagnosed with ACR/EULAR (American College of Rheumatology/European League against Rheumatism) 2010 criteria was enrolled in this prospective, observational and analytic research study...
February 15, 2018: Open Access Macedonian Journal of Medical Sciences
Johanna Sigaux, Jérôme Biton, Emma André, Luca Semerano, Marie-Christophe Boissier
Pollution has long been incriminated in many cardiovascular and respiratory diseases. More recently, studies evaluated the potential role for particulate pollutants in autoimmune diseases, including rheumatoid arthritis (RA). The incidence of RA was found to be higher in urban areas. Living near air pollution emitters was associated with higher risks of developing RA and of producing RA-specific autoantibodies. Nevertheless, no strong epidemiological evidence exists to link one or more specific air pollution particles to RA...
March 7, 2018: Joint, Bone, Spine: Revue du Rhumatisme
Meghdad Abdollahpour-Alitappeh, Seyed Masoud Hashemi Karouei, Majid Lotfinia, Amir Amanzadeh, Mahdi Habibi-Anbouhi
Rituximab is a chimeric monoclonal antibody directed against B-lymphocyte specific antigen CD20, which is used for the treatment of B-cell malignancies. However, the effectiveness of rituximab is limited partly due to treatment resistance. The aim of this study was to develop rituximab-based antibody drug conjugate (ADC) to enhance rituximab activity. In this study, monomethyl auristatin E (MMAE) was covalently conjugated to dithiothreitol -reduced rituximab via a valine-citrulline peptide linker (rituximab-vcMMAE)...
March 9, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Sarah Twigg, Elena Nikiphorou, Jackie L Nam, Laura Hunt, Kulveer Mankia, Peta Elizabeth Pentony, Jane E Freeston, Ai Lyn Tan, Paul Emery
Objectives: To compare comorbidities in a cohort of cyclic citrullinated peptide (CCP) antibody positive patients without or prior to onset of inflammatory arthritis (IA) to those in patients with early IA. Methods: Baseline data from two established cohorts were used. The first recruited people at risk of IA: CCP antibody positive cases without IA (CCP Cohort, n  = 296). The second cohort [the Inflammatory Arthritis CONtinuum study (IACON)] recruited patients with early IA ( n  = 725)...
2018: Frontiers in Medicine
Isabel Lopez-Oliva, Akshay D Paropkari, Shweta Saraswat, Stefan Serban, Zehra Yonel, Praveen Sharma, Paola de Pablo, Karim Raza, Andrew Filer, Iain Chapple, Thomas Dietrich, Melissa M Grant, Purnima S Kumar
OBJECTIVES: Studies that demonstrate an association between rheumatoid arthritis (RA) and dysbiotic oral microbiomes are often confounded by the presence of extensive periodontitis in these individuals. Therefore, the present investigation sought to investigate the role of RA in modulating the periodontal microbiome by comparing periodontally healthy individuals with and without RA. METHODS: Subgingival plaque was collected from was collected periodontally healthy individuals (22 with and 19 without RA), and 16S gene sequenced on the Ilumina MiSeq platform...
March 7, 2018: Arthritis & Rheumatology
Jin-Ju Byeon, Min-Ho Park, Seok-Ho Shin, Byeong Ill Lee, Yuri Park, Jangmi Choi, Nahye Kim, Yeonjae Kang, Young G Shin
A single hybrid affinity-captured-LC-TOF-MS/MS method was developed and applied for the quantification of total antibody, antibody conjugated drug and free payload of antibody drug conjugate (ADC). Adcetris®, one of the valine-citrulline MMAE (vc-MMAE) conjugated ADC, was used as a model ADC compound. A quadratic regression (weighted 1/concentration) was used to fit calibration curves over the concentration range of 30.65-613.00 ng/mL with an equation y=ax2 +bx+c for the acDrug of Adcetris®. The qualification run met the acceptance criteria of ± 25% accuracy and precision values for quality control samples...
March 5, 2018: Biomedical Chromatography: BMC
Robby Engelmann, Sven Nekarda, Daniela Kuthning, Christian Kneitz, Brigitte Müller-Hilke
The treatment options for patients suffering from rheumatoid arthritis expanded over the last years. However, reliable biomarkers to guide therapy decisions are still warranted. Therefore, we here evaluated the value of antibodies against citrullinated peptide antigens (ACPA) IgG subclasses and peripheral blood antigen presenting cells as biomarkers to monitor and predict therapy response of patients with rheumatoid arthritis. Thirty-four ACPA-positive RA patients were enrolled and monitored for 3 months after therapy begin...
March 3, 2018: Clinical Rheumatology
David H Margulies
The molecular immunologist's dream is to elucidate a fundamental biochemical process that explains the basis of an affliction that affects millions of people, and that, precisely understood, might yield a rational approach to diagnosis, prevention, or therapy. In this issue of JBC, Ting et al. report proteomic, biochemical, and structural analyses that better explain how the antigen-presenting HLA-DR4 molecules bind citrullinated peptides to provoke rheumatoid arthritis (RA), a chronic autoimmune disease that affects 0...
March 2, 2018: Journal of Biological Chemistry
Harri Härmä, Natalia Tong-Ochoa, Arjan J van Adrichem, Ilian Jelesarov, Krister Wennerberg, Kari Kopra
Post-translational modification (PTM) of proteins plays essential regulatory roles in a variety of pathological conditions. Reliable and practical assays are required to accelerate the discovery of inhibitors and activators for PTM related diseases. Today, methodologies are based on specific or group-specific PTM recognition of e.g. phosphate for kinase activity without extending to other type of PTMs. Here we have established a universal time-resolved luminescence assay on a peptide-break platform for the direct detection of wide variety of PTMs...
March 2, 2018: Chemical Communications: Chem Comm
Kutty Selva Nandakumar
Rheumatoid arthritis (RA) is a polygenic and multifactorial syndrome. Many complex immunological and genetic interactions are involved in the final outcome of the clinical disease. Autoantibodies (rheumatoid factors, anti-citrullinated peptide/protein antibodies) are present in RA patients' sera for a long time before the onset of clinical disease. Prior to arthritis onset, in the autoantibody response, epitope spreading, avidity maturation, and changes towards a pro-inflammatory Fc glycosylation phenotype occurs...
February 28, 2018: International Journal of Molecular Sciences
Nicole Hartwig Trier, Bettina Eide Holm, Julie Heiden, Ole Slot, Henning Locht, Hanne Lindegaard, Anders Svendsen, Christoffer Tandrup Nielsen, Søren Jacobsen, Elke Theander, Gunnar Houen
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Anti-citrullinated protein antibodies (ACPA) are crucial for the serological diagnosis of RA, where Epstein-Barr virus (EBV) has been suggested to be an environmental agent in triggering the onset of the disease. This study aimed to analyse antibody reactivity to citrullinated EBV nuclear antigen-2 (EBNA-2) peptides from three different EBV strains (B95-8, GD1 and AG876) using streptavidin capture enzyme-linked immunosorbent assay. One peptide, only found in a single strain (AG876), obtained a sensitivity and specificity of 77% and 95%, respectively and showed high sequence similarity to the filaggrin peptide originally used for ACPA detection...
February 27, 2018: Scientific Reports
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
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
Takahisa Suzuki, Shoichi Fukui, Kunihiko Umekita, Junya Miyamoto, Masataka Umeda, Ayako Nishino, Akitomo Okada, Tomohiro Koga, Shin-Ya Kawashiri, Naoki Iwamoto, Kunihiro Ichinose, Mami Tamai, Keita Fujikawa, Toshiyuki Aramaki, Akinari Mizokami, Naoki Matsuoka, Yukitaka Ueki, Katsumi Eguchi, Shuntaro Sato, Toshihiko Hidaka, Tomoki Origuchi, Akihiko Okayama, Atsushi Kawakami, Hideki Nakamura
OBJECTIVES: We evaluated the effectiveness of tumor necrosis factor (TNF) inhibitors for the treatment of human T-lymphotropic virus type 1 (HTLV-I)-positive rheumatoid arthritis (RA) patients in an HTLV-I endemic area. METHODS: We conducted an observational study of 585 RA patients for whom TNF inhibitors were newly introduced as a first biologic disease-modifying antirheumatic drug (bDMARD) in an HTLV-I endemic area in southwestern Japan. RESULTS: Fifty patients (8...
February 22, 2018: Arthritis & Rheumatology
Mario Berth, Sofie Willaert, Carol De Ridder
BACKGROUND: The detection of anti-cyclic citrullinated peptide (anti-CCP) IgG antibodies in blood is mainly used for the diagnosis of rheumatoid arthritis. Falsely elevated anti-CCP IgG antibodies due to anti-streptavidin IgG antibodies were suspected in our laboratory. METHODS: In this study, we evaluated, in a standardized approach, the prevalence of anti-streptavidin IgG antibodies in a primary care setting and the effect of anti-streptavidin IgG antibodies on anti-CCP IgG assays from three different important commercial manufacturers (Abbott, Roche Diagnostics, Thermo Fisher Scientific)...
February 21, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
Akihisa Haraguchi, Hisakata Yamada, Masakazu Kondo, Ken Okazaki, Jun-Ichi Fukushi, Akiko Oyamada, Yasunobu Yoshikai, Yasuharu Nakashima
OBJECTIVES: Since the presence of IgM antibodies is a hallmark of ongoing immune response, we aimed to identify immunologically active rheumatoid arthritis (RA) patients by detecting IgM anti-citrullinated protein antibody (ACPA) levels. METHODS: IgM ACPA levels were determined in the serum of 176 RA patients by enzyme-linked immunosorbent assay, in which parameters of reactivity against citrullinated and non-citrullinated peptides were compared to ensure the specificity...
February 14, 2018: Clinical and Experimental Rheumatology
Yang Liu, Hongyan Wen
OBJECTIVE: To determine if patients with rheumatoid arthritis (RA) are at risk of vitamin D deficiency and whether the levels of vitamin D are correlated with clinical parameters in RA. METHODS: A total of 280 treatment-naïve RA patients, and 140 age- and sex-matched healthy volunteers were enrolled. Serum levels of 1,25-dihydroxycholecalciferol (1,25(OH)2 D3 ), the active form of vitamin D, were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations of 1,25(OH)2 D3 less than 25 ng/mL were defined as insufficient...
February 19, 2018: Zeitschrift Für Rheumatologie
Jun Inamo, Yuko Kaneko, Tsutomu Takeuchi
Reports about immune-related adverse events (IrAEs) induced by immune checkpoint inhibitors (ICIs) have been increasing. Although the importance of understanding joint involvement and myalgia as an IrAE has grown, little is known about its characteristics. The aim of this study was to investigate the incidence and clinical characteristics of articular IrAEs. We reviewed 133 patients who were treated with ICIs in our institution and referred to our rheumatologic. Among them, 2 (1.5%) developed arthritis during the use of anti-PD-1 inhibitor, and there was one patient with joint pain after anti-PD-L1 inhibitor who was referred to our department from another institution...
February 17, 2018: Clinical Rheumatology
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