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Citrullinated peptides

Bryant R England, Geoffrey M Thiele, Ted R Mikuls
PURPOSE OF REVIEW: This article reviews recent literature on the origin and pathogenic role of anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA). RECENT FINDINGS: ACPAs and ACPA-immune complexes interact with immune cells to facilitate articular inflammation. Findings from recent in vitro and in vivo studies are congruent with epidemiologic observations in RA supporting a pathogenic role of ACPAs. SUMMARY: ACPAs target proteins/peptides with citrullinated epitopes and serve as informative RA biomarkers...
October 13, 2016: Current Opinion in Rheumatology
Vikram Londhey, Meghav M Shah
INTRODUCTION: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been considered very specific for rheumatoid arthritis (RA). Some studies have shown that these antibodies can be positive in infectious diseases like TB, HIV, etc. METHODS: Fifty patients of tuberculosis both pulmonary and extra-pulmonary were enrolled in the study from inpatient and outpatient departments from May 2012 to November 2013. Anti-CCP antibody test was done in all the patient by ELISA...
May 2016: Journal of the Association of Physicians of India
Maria C Lebre, Pedro L Vieira, Man Wai Tang, Saïda Aarrass, Boy Helder, Thomas Newsom-Davis, Paul P Tak, Gavin R Screaton
Bone and cartilage destruction is one of the key manifestations of rheumatoid arthritis (RA). Although the role of T helper (Th)17 cells in these processes is clear, the role of IL-21-producing cells T cells has been neglected. We sought to investigate the role of IL-21 in RA by focusing on the functional characteristics of the main producers of this cytokine, synovial CD4(+)IL-21(+) T cells. We show that the frequency of both synovial fluid (SF) CD4(+)IL-21(+) or CD4(+)IL-21(+)TNF(+) T cells in patients with RA was significantly higher compared with patients with psoriatic arthritis (PsA)...
October 12, 2016: Journal of Leukocyte Biology
Tomoya Shibahara, Tomonaga Matsushita, Ryu Matsuo, Yoshihisa Fukushima, Kenji Fukuda, Hiroshi Sugimori, Masahiro Kamouchi, Takanari Kitazono, Tetsuro Ago
Rheumatoid meningoencephalitis (RM) is a rare complication of rheumatoid arthritis (RA). This report describes a 63-year-old man with complaints of high-grade fever, headache, and vomiting for several days before admission. Both his serum and cerebrospinal fluid were positive for anti-cyclic citrullinated peptide (CCP) antibody and rheumatoid factor, and contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging (MRI) showed abnormal gadolinium enhancement of the meninges and high-intensity lesions in the subarachnoid spaces...
May 2016: Case Reports in Neurology
Eric Hatterer, Limin Shang, Pierre Simonet, Suzanne Herren, Bruno Daubeuf, Stéphanie Teixeira, James Reilly, Greg Elson, Robert Nelson, Cem Gabay, Jeremy Sokolove, Iain B McInnes, Marie Kosco-Vilbois, Walter Ferlin, Emmanuel Monnet, Cristina De Min
BACKGROUND: Increased expression of toll-like receptor 4 (TLR4) and its endogenous ligands, is characteristic of rheumatoid arthritis (RA) synovitis. In this study, we evaluated how these TLR4 ligands may drive pathogenic processes and whether the fine profiling of anti-citrullinated protein antibodies (ACPA) based on their target specificity might provide a simple means to predict therapeutic benefit when neutralizing TLR4 in this disease. METHODS: The capacity of RA synovial fluids (RASF) to stimulate cytokine production in monocytes from patients with RA was analyzed by ELISA...
October 6, 2016: Arthritis Research & Therapy
Martha Adriana Badillo-Soto, Mayra Rodríguez-Rodríguez, María Elena Pérez-Pérez, Leonel Daza-Benitez, Juan José Bollain-Y-Goytia, Miguel Angel Carrillo-Jiménez, Esperanza Avalos-Díaz, Rafael Herrera-Esparza
OBJECTIVE: The molecular mechanism of citrullination involves the calcium-dependent peptidylarginine deiminase (PAD) family of enzymes. These enzymes induce a stereochemical modification of normal proteins and transform them into autoantigens, which in rheumatoid arthritis trigger a complex cascade of joint inflammatory events followed by chronic synovitis, pannus formation, and finally, cartilage destruction. By hypothesizing that PAD2 and PAD4 enzymes produce autoantigens, we investigated five possible synovial protein targets of PAD enzymes...
June 2016: Eur J Rheumatol
Laura Geraldino-Pardilla, Jon T Giles, Jeremy Sokolove, Afshin Zartoshti, William H Robinson, Matthew Budoff, Robert Detrano, Sabahat Bokhari, Joan M Bathon
OBJECTIVE: Citrullinated proteins have been found within atherosclerotic plaque. However, to date studies evaluating the association between anti-citrullinated peptide antibodies (ACPAs) and imaging measures of atherosclerosis in patients with rheumatoid arthritis (RA) have been limited to citrullinated-fibrinogen or citrullinated-vimentin seroreactivities and rendered contradictory results. Therefore, our objective was to evaluate this association using an extended panel of ACPAs in a larger sample of RA patients without clinical cardiovascular disease (CVD)...
October 1, 2016: Arthritis Care & Research
Wildéa Lice de Carvalho Jennings Pereira, Edna Maria Vissoci Reiche, Ana Paula Kallaur, Sayonara Rangel Oliveira, Andréa Name Colado Simão, Marcell Alysson Batisti Lozovoy, Lucas José Vaz Schiavão, Paula Raquel do Vale Pascoal Rodrigues, Daniela Frizon Alfieri, Tamires Flauzino, Damacio Ramón Kaimen-Maciel
OBJECTIVE: The aim of this study was to report the frequency of autoimmune disorders and autoantibodies in 22 patients with neuromyelitis optica (NMO), as well as whether the seropositivity for autoantibodies differs between anti-aquaporin 4 (AQP4) positive and AQP4 negative NMO patients. METHODS: Demographic, medical records, and a profile of autoantibodies were evaluated in 22 NMO patients, including AQP4, anti-thyroid-stimulating hormone receptor, antinuclear antibodies (ANA), anti-thyroperoxidase (anti-TPO), anti-thyroglobulin (anti-Tg), anti-double-stranded DNA, anti-neutrophil cytoplasmic, anti-cyclic citrullinate peptide, rheumatoid factor, anti-SSA/Ro, anti-SSB/La, anti-Smith antibodies (anti-Sm), anti-ribonucleoprotein, anti-nucleosome, and anti-Scl70...
October 3, 2016: Acta Neuropsychiatrica
Chander Grover, Bineeta Kashyap, Deepashree Daulatabad, Amit Dhawan, Iqbal R Kaur
BACKGROUND: Anti-cyclic citrullinated peptides (CCPs) are autoantibodies directed against citrullinated peptides. Rheumatoid factor (RF), an antibody against the Fc portion of IgG, is known to form immune complexes and contribute to the etiopathogenesis of various skin disorders. C-reactive protein (CRP), an acute-phase protein, increases following secretion of interleukin-6 from macrophages and T cells. Anti-CCP, RF, and CRP are well-established immune-markers, their diagnostic potential in immune-mediated skin disorders remains less widely studied...
September 2016: Indian Journal of Dermatology
Francesca Romana Spinelli, Arbi Pecani, Fabrizio Conti, Riccardo Mancini, Cristiano Alessandri, Guido Valesini
Coronary heart disease is the main cause of mortality in patients with rheumatoid arthritis (RA), a disease known to be associated with accelerated atherosclerosis. The role of inflammation and immunity in atherosclerotic process offers possible explanations for the increased cardiovascular risk in patients with RA. The immune response to citrullinated peptides has been extensively studied in RA; antibodies directed to citrullinated peptides are now a cornerstone for RA diagnosis. However, few studies have investigated the response to citrullinated peptides and the development of atherosclerotic plaque...
September 2016: Journal of International Medical Research
Basant M Elnady, Naglaa M Kamal, Raneyah H M Shaker, Amal F Soliman, Waleed A Hasan, Hamed A Alghamdi, Mohammed M Algethami, Mohamed Bilal Jajah
Autoimmune diseases are considered the 3rd leading cause of morbidity and mortality in the industrialized countries. Autoimmune thyroid diseases (ATDs) are associated with high prevalence of nonorgan-specific autoantibodies, such as antinuclear antibodies (ANA), antidouble-stranded deoxyribonucleic acid (anti-dsDNA), antiextractable-nuclear antigens (anti-ENAs), rheumatoid factor (RF), and anticyclic-citrullinated peptides (anti-CCP) whose clinical significance is unknown.We aimed to assess the prevalence of various nonorgan-specific autoantibodies in patients with ATD, and to investigate the possible association between these autoantibodies and occurrence of rheumatic diseases and, if these autoantibodies could be considered as predictor markers for autoimmune rheumatic diseases in the future...
September 2016: Medicine (Baltimore)
Tue Bjerg Bennike, Torkell Ellingsen, Henning Glerup, Ole Kristian Bonderup, Thomas Gelsing Carlsen, Michael Kruse Kruse Meyer, Martin Bøgsted, Gunna Christiansen, Svend Birkelund, Vibeke Andersen, Allan Stensballe
Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. To gain new insight into the systemic immune manifestations of RA, we characterized the colon mucosa proteome from 11 RA-patients and 10 healthy controls. The biopsies were extracted by colonoscopy and analyzed by label-free quantitative proteomics, enabling the quantitation of 5,366 proteins. The abundance of dihydrofolate reductase (DHFR) was statistically significantly increased in RA-patient biopsies compared to controls, and correlated with the administered dosage of methotrexate (MTX), the most frequently prescribed immunosuppressive drug for RA...
September 14, 2016: Journal of Proteome Research
Hui-Chun Yu, Pei-Hsuan Lai, Ning-Sheng Lai, Hsien-Bin Huang, Malcolm Koo, Ming-Chi Lu
The objective of this study was to investigate the presence and titer of anti-carbamylated 78-kDa glucose-regulated protein (anti-CarGRP78) antibody in serum from controls, and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS). Thirty-three RA patients, 20 SLE patients, 20 pSS patients, and 20 controls were enrolled from our outpatient clinic. GRP78 was cloned and carbamylated. Serum titers of anti- cyclic citrullinated peptides (anti-CCP), anti-GRP78, and anti-CarGRP78 were measured with an enzyme-linked immunosorbent assay...
2016: International Journal of Molecular Sciences
Elana J Bernstein, R Graham Barr, John H M Austin, Steven M Kawut, Ganesh Raghu, Jessica L Sell, Eric A Hoffman, John D Newell, Jubal R Watts, P Hrudaya Nath, Sushil K Sonavane, Joan M Bathon, Darcy S Majka, David J Lederer
BACKGROUND: Adults with interstitial lung disease (ILD) often have serologic evidence of autoimmunity of uncertain significance without overt autoimmune disease. We examined associations of rheumatoid arthritis (RA)-associated antibodies with subclinical ILD in community-dwelling adults. METHODS: We measured serum rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) and high attenuation areas (HAAs; CT attenuation values between -600 and -250 Hounsfield units) on cardiac CT in 6736 community-dwelling US adults enrolled in the Multi-Ethnic Study of Atherosclerosis...
September 8, 2016: Thorax
Linda Johansson, Natalia Sherina, Nastya Kharlamova, Barbara Potempa, Barbro Larsson, Lena Israelsson, Jan Potempa, Solbritt Rantapää-Dahlqvist, Karin Lundberg
BACKGROUND: The periodontal pathogen Porphyromonas gingivalis is hypothesized to be important in rheumatoid arthritis (RA) aetiology by inducing production of anti-citrullinated protein antibodies (ACPA). We have shown that ACPA precede RA onset by years, and that anti-P. gingivalis antibody levels are elevated in RA patients. The aim of this study was to investigate whether anti-P. gingivalis antibodies pre-date symptom onset and ACPA production. METHODS: A case-control study (251 cases, 198 controls) was performed within the Biobank of Northern Sweden...
2016: Arthritis Research & Therapy
Mitali Bidkar, Robert Vassallo, David Luckey, Michele Smart, Kelly Mouapi, Veena Taneja
Rheumatoid arthritis (RA) is an autoimmune disease marked by chronic synovial inflammation and both, genetic and environmental factors are involved in its pathogenesis. Human leukocyte antigen (HLA) DRB1*0401 is associated with susceptibility to develop RA, while cigarette smoke (CS) exposure promotes seropositive disease with increased severity in DRB1*0401+ individuals. Smokers have higher levels of antibodies against citrullinated peptides. In this study, we determined whether the response to a known autoantigen, Vimentin (Vim) is shared epitope specific and how CS influences this response using transgenic-mice carrying RA-susceptible,*0401, and -resistant, *0402, genes...
2016: PloS One
Christian C Yost, Hansjörg Schwertz, Mark J Cody, Jared A Wallace, Robert A Campbell, Adriana Vieira-de-Abreu, Claudia V Araujo, Sebastian Schubert, Estelle S Harris, Jesse W Rowley, Matthew T Rondina, James M Fulcher, Curry L Koening, Andrew S Weyrich, Guy A Zimmerman
Neutrophil granulocytes, also called polymorphonuclear leukocytes (PMNs), extrude molecular lattices of decondensed chromatin studded with histones, granule enzymes, and antimicrobial peptides that are referred to as neutrophil extracellular traps (NETs). NETs capture and contain bacteria, viruses, and other pathogens. Nevertheless, experimental evidence indicates that NETs also cause inflammatory vascular and tissue damage, suggesting that identifying pathways that inhibit NET formation may have therapeutic implications...
October 3, 2016: Journal of Clinical Investigation
Koji Tamai, Harukazu Yoshimatsu, Toshiharu Saito, Hirofumi Matsuoka, Nobuhiko Okada, Yasuko Koma, Akiko Otsuka, Nao Oda, Sayaka Inoue, Sachie Kume, Yujiro Suzuki
BACKGROUND: Autoimmune involvement in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) has been proposed, and autoantibodies are a hallmark of autoimmunity. This study aimed to compare the autoantibody profiles of asthma and COPD, and the relationship between autoantibodies and features of these diseases. METHODS: We recruited 110 asthma patients and 92 COPD patients for a prospective study. Six autoantibody types were evaluated: antinuclear antibody, anti-cytoplasmic antibodies, rheumatoid factor, anti-cyclic citrullinated peptide antibody, myeloperoxidase-anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and proteinase 3-ANCA...
August 31, 2016: Allergology International: Official Journal of the Japanese Society of Allergology
Jayanth Doss, Huan Mo, Robert J Carroll, Leslie J Crofford, Joshua C Denny
OBJECTIVE: The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)-based phenome-wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA. METHODS: A validated algorithm identified RA subjects from the de-identified EHR. Serotypes were determined by values of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA)...
September 2, 2016: Arthritis & Rheumatology
Koen M J Janssen, Johanna Westra, Paulina Chalan, Annemieke M H Boots, Menke J de Smit, Arie Jan van Winkelhoff, Arjan Vissink, Elisabeth Brouwer
OBJECTIVE: Seropositive arthralgia patients (SAP) are at high risk of developing rheumatoid arthritis (RA). This prospective study aimed to determine whether altered peripheral regulatory T-cells (Tregs) and defined subsets, besides a broadened anti-citrullinated protein antibody (ACPA) response, may qualify as biomarkers for RA development in SAP. METHODS: Thirty-four consecutive SAP were prospectively assessed every 6 months for minimally 2 years. At inclusion, peripheral Treg (CD4+CD25+FoxP3+) numbers and subsets, defined as CD45RA+FoxP3low naive Tregs (Fr I), CD45RA-FoxP3high activated Tregs (Fr II) and CD45RA-FoxP3low non-Tregs (Fr III), were compared to age- and sex-matched healthy controls (HC, n = 16) and treatment-naive RA patients (n = 12)...
2016: PloS One
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