scholarly journals SAT0691 Influence of smoking in the expression of chronic periodontitis and anti-citrullinated proteins antibodies in rheumatoid arthritis

2017 ◽  
Author(s):  
J González Febles ◽  
JL Rodríguez Garnier ◽  
F Sánchez Alonso ◽  
S Dadlani ◽  
Y Barrios ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chronic Periodontitis ◽  
Citrullinated Proteins

scholarly journals Identification of potential autoantigens in anti-CCP-positive and anti-CCP-negative rheumatoid arthritis using citrulline-specific protein arrays

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas B. G. Poulsen ◽  
Dres Damgaard ◽  
Malene M. Jørgensen ◽  
Ladislav Senolt ◽  
Jonathan M. Blackburn ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein Microarray ◽  
Specific Protein ◽  
Immune Reactivity ◽  
Igg Antibodies ◽  
Native Proteins ◽  
Array Technology ◽  
Citrullinated Proteins ◽  
Folded Proteins

AbstractThe presence or absence of autoantibodies against citrullinated proteins (ACPAs) distinguishes two main groups of rheumatoid arthritis (RA) patients with different etiologies, prognoses, disease severities, and, presumably, disease pathogenesis. The heterogeneous responses of RA patients to various biologics, even among ACPA-positive patients, emphasize the need for further stratification of the patients. We used high-density protein array technology for fingerprinting of ACPA reactivity. Identification of the proteome recognized by ACPAs may be a step to stratify RA patients according to immune reactivity. Pooled plasma samples from 10 anti-CCP-negative and 15 anti-CCP-positive RA patients were assessed for ACPA content using a modified protein microarray containing 1631 different natively folded proteins citrullinated in situ by protein arginine deiminases (PADs) 2 and PAD4. IgG antibodies from anti-CCP-positive RA plasma showed high-intensity binding to 87 proteins citrullinated by PAD2 and 99 proteins citrullinated by PAD4 without binding significantly to the corresponding native proteins. Curiously, the binding of IgG antibodies in anti-CCP-negative plasma was also enhanced by PAD2- and PAD4-mediated citrullination of 29 and 26 proteins, respectively. For only four proteins, significantly more ACPA binding occurred after citrullination with PAD2 compared to citrullination with PAD4, while the opposite was true for one protein. We demonstrate that PAD2 and PAD4 are equally efficient in generating citrullinated autoantigens recognized by ACPAs. Patterns of proteins recognized by ACPAs may serve as a future diagnostic tool for further subtyping of RA patients.

Rheumatoid Arthritis: Etiology and Pathogenesis

2014 ◽  
Author(s):  
Gary S. Firestein ◽  
Anna-Karin H. Ekwall
Keyword(s):  
Rheumatoid Arthritis ◽  
Intracellular Signaling ◽  
Cartilage Damage ◽  
Signs And Symptoms ◽  
American College Of Rheumatology ◽  
European League Against Rheumatism ◽  
Citrullinated Proteins ◽  
Definition Of

Rheumatoid arthritis (RA) is among the most common forms of chronic inflammatory arthritis. It affects approximately 1% of adults and is two to three times more prevalent in women than in men. There are no specific laboratory tests for RA; diagnosis depends on a constellation of signs and symptoms that can be supported by serology and radiographs. The disease evolves over many years as a consequence of repeated environmental stress causing inflammation and immune activation followed by a breakdown of tolerance in individuals with a specific genetic background. This review describes the definition of RA; its etiology, including genetics, infections, the role of smoking and citrullination of proteins, and epigenetic mechanisms; and its pathogenesis, including synovial histopathology, bone and cartilage damage, adaptive and innate immunity, and the role of cytokines and intracellular signaling. Tables include the 1987 American Rheumatism Association criteria for the classification of RA and the 2010 American College of Rheumatology/European League Against Rheumatism classification for RA. Figures show citrullinated proteins in airway cells, a section of a proliferative synovium from a patient with a classic RA, and scalloped regions of erosion at the junction between a proliferative inflamed rheumatoid synovium and the bone. This review contains 3 highly rendered figures, 2 tables, and 71 references.

scholarly journals Reduced Anti-Histone Antibodies and Increased Risk of Rheumatoid Arthritis Associated with a Single Nucleotide Polymorphism in PADI4 in North Americans

2019 ◽  
Vol 20 (12) ◽  
pp. 3093 ◽  
Author(s):  
Aisha M. Mergaert ◽  
Mandar Bawadekar ◽  
Thai Q. Nguyen ◽  
Laura Massarenti ◽  
Caitlyn L. Holmes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Nucleotide Polymorphism ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Rheumatoid Arthritis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Rheumatoid Arthritis Diagnosis ◽  
North Americans ◽  
Increased Risk ◽  
Citrullinated Proteins

Autoantibodies against citrullinated proteins are a hallmark of rheumatoid arthritis, a destructive inflammatory arthritis. Peptidylarginine deiminase 4 (PAD4) has been hypothesized to contribute to rheumatoid arthritis by citrullinating histones to induce neutrophil extracellular traps (NETs), which display citrullinated proteins that are targeted by autoantibodies to drive inflammation and arthritis. Consistent with this theory, PAD4-deficient mice have reduced NETs, autoantibodies, and arthritis. However, PAD4′s role in human rheumatoid arthritis is less clear. Here, we determine if single nucleotide polymorphism rs2240335 in PADI4, whose G allele is associated with reduced PAD4 in neutrophils, correlates with NETs, anti-histone antibodies, and rheumatoid arthritis susceptibility in North Americans. Control and rheumatoid arthritis subjects, divided into anti-cyclic citrullinated peptide (CCP) antibody positive and negative groups, were genotyped at rs2240335. In homozygotes, in vitro NETosis was quantified in immunofluorescent images and circulating NET and anti-histone antibody levels by enzyme linked immunosorbent assay (ELISA). Results were compared by t-test and correlation of rheumatoid arthritis diagnosis with rs2240335 by Armitage trend test. NET levels did not significantly correlate with genotype. G allele homozygotes in the CCP− rheumatoid arthritis group had reduced anti-native and anti-citrullinated histone antibodies. However, the G allele conferred increased risk for rheumatoid arthritis diagnosis, suggesting a complex role for PAD4 in human rheumatoid arthritis.

scholarly journals Citrullinated vimentin as an important antigen in immune complexes from synovial fluid of rheumatoid arthritis patients with antibodies against citrullinated proteins

2010 ◽  
Vol 12 (4) ◽  
pp. R132 ◽  
Author(s):  
Katleen Van Steendam ◽  
Kelly Tilleman ◽  
Marlies De Ceuleneer ◽  
Filip De Keyser ◽  
Dirk Elewaut ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Immune Complexes ◽  
Citrullinated Proteins ◽  
Citrullinated Vimentin

Antibodies to native and citrullinated RA33 (hnRNP A2/B1) challenge citrullination as the inciting principle underlying loss of tolerance in rheumatoid arthritis

2016 ◽  
Vol 75 (11) ◽  
pp. 2022-2028 ◽  
Author(s):  
Maximilian F Konig ◽  
Jon T Giles ◽  
Peter A Nigrovic ◽  
Felipe Andrade
Keyword(s):  
Rheumatoid Arthritis ◽  
Splice Variants ◽  
Humoral Response ◽  
Native Protein ◽  
Erosive Disease ◽  
Rapid Disease Progression ◽  
Citrullinated Proteins ◽  
Loss Of Tolerance ◽  
Disease Initiation ◽  
Major Target

BackgroundAnti-citrullinated protein antibodies (ACPAs) are the hallmark of rheumatoid arthritis (RA). Protein citrullination is believed to drive autoantigen selection in RA. Nonetheless, several autoantigens in RA are targeted as native (unmodified) proteins. Here, the study of hnRNP A2/B1 (RA33) provides a framework to understand the humoral response to native and citrullinated autoantigens in RA.MethodsRA synovial fluid (SF) cells were analysed by immunoblotting and mass spectrometry. RA33 was cloned from RASF cells and splice variants expressed as recombinant proteins. Antibodies against native and citrullinated RA33 were characterised by ELISA, immunoblotting and immunoprecipitation.ResultsRA33 is citrullinated in the rheumatoid joint and targeted either as a citrullinated or native protein in distinct patient subsets with RA. A novel splice variant (hnRNP B1b) previously associated with disease initiation in experimental arthritis was identified in the RA joint and acts as the major target of the anti-RA33 response. Antibodies exclusively targeting citrullinated RA33 were positively associated with disease duration and erosive disease. In contrast, anti-(native) RA33 antibodies were detected almost exclusively in early RA and identified patients with low radiographic erosion scores. Finally, a unique subset of double-reactive patients demonstrated intermediate severity, but rapid disease progression, suggesting a transitional disease phase in the evolution of an anti-native protein antibody to ACPA response in RA.ConclusionsThese data suggest that native and citrullinated proteins targeted by autoantibodies in RA may be part of a single antibody system and challenge the paradigm of citrullination as the unifying principle underlying loss of tolerance in RA.

SAT0100 Association between Chronic Periodontitis and Clinical Profile of Rheumatoid Arthritis

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 701.2-701
Author(s):  
B. Rodríguez-Lozano ◽  
J.L. Garnier Rodríguez ◽  
J. González Febles ◽  
S. Dadlani ◽  
B. Tejera Segura ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chronic Periodontitis ◽  
Clinical Profile
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