scholarly journals The Role of Citrullinated Protein Antibodies in Predicting Erosive Disease in Rheumatoid Arthritis: A Systematic Literature Review and Meta-Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
A. A. Jilani ◽  
C. G. Mackworth-Young
Keyword(s):  
Rheumatoid Arthritis ◽  
Meta Analysis ◽  
Cost Effective ◽  
Erosive Disease ◽  
Peptide Antigens ◽  
Cost Effective Treatment ◽  
Joint Erosions ◽  
Citrullinated Protein ◽  
Citrullinated Peptide

Background. Autoantibodies to citrullinated peptides have been shown to be valuable in the diagnosis of rheumatoid arthritis (RA). The expanding repertoire of antibodies to citrullinated peptide antigens (ACPA) has been a topic of great interest in recent reviews and research studies, as has the ability of these autoantibodies to predict disease outcome.Objectives. The aim of this review was to provide an update on the relevance of ACPA as prognostic markers in RA. The ability to identify patients predisposed to an aggressive outcome at the time of initial diagnosis greatly facilitates the selection of appropriate and cost-effective treatment.Methods. A systematic review of the literature was carried out. Studies from 1967 up to June 2014 with data on prognostic value of ACPA were included. Quality assessment was done by using the modified Hayden list for prognostic studies. Meta-analysis was performed using BioStat software.Results. The results of 25 studies were selected for the final review. A total of 6421 patients with RA were included, mainly in inception cohorts, with follow-up duration ranging from one year to ten years. All studies carried prognostic data on all available isotypes of anticyclic citrullinated protein (CCP), while four had data on antimutated citrullinated vimentin (MCV). There was a single relevant study each on anticitrullinated enolase peptide 1 (CEP1) and antichimaeric fibrin/filaggrin citrullinated peptide 1 (CFFCP1). All studies showed ACPA to be strong predictors of joint erosions in RA. Other factors, particularly baseline erosions, showed an additive effect. Anti-MCV appeared to be a marker of a more aggressive form of disease. Ten studies had data on which a meta-analysis could be performed. This gave an overall odds ratio of 4.85 for ACPA (anti-CCP/MCV) positivity being predictive for the development of joint erosions. Two studies with data on anti-CEP1 and anti-CFFCP1 also showed this positive predictive role of ACPA for joint erosions.Conclusions. ACPA are strong predictors of severity in RA. Their use should be part of routine rheumatology practice.

scholarly journals Alcohol consumption is associated with decreased risk of rheumatoid arthritis: results from two Scandinavian case–control studies

2008 ◽  
Vol 68 (2) ◽  
pp. 222-227 ◽  
Author(s):  
H Källberg ◽  
S Jacobsen ◽  
C Bengtsson ◽  
M Pedersen ◽  
L Padyukov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Alcohol Consumption ◽  
Case Control ◽  
Inverse Association ◽  
Case Control Studies ◽  
Peptide Antigens ◽  
Independent Case ◽  
Citrullinated Peptide ◽  
Recent Demonstration

Objectives:To determine the association between risk of rheumatoid arthritis (RA) and alcohol consumption in combination with smoking and HLA-DRB1 shared epitope (SE).Methods:Data from two independent case–control studies of RA, the Swedish EIRA (1204 cases and 871 controls) and the Danish CACORA (444 cases and 533 controls), were used to estimate ORs of developing RA for different amounts of alcohol consumed.Results:Alcohol consumption was significantly more common in controls (p<0.05) and dose-dependently associated with reduced risk of RA (p for trend <0.001) in both studies. Among alcohol consumers, the quarter with the highest consumption had a decreased risk of RA of the order of 40–50% compared with the half with the lowest consumption (EIRA, OR = 0.5 (95% CI 0.4 to 0.6); CACORA, OR = 0.6 (95% CI 0.4 to 0.9)). For the subset of RA that is seropositive for antibodies to citrullinated peptide antigens, alcohol consumption reduced the risk most in smokers carrying HLA-DRB1 SE alleles.Conclusions:The observed inverse association between alcohol intake and risk of RA and the recent demonstration of a preventive effect of alcohol in experimental arthritis indicate that alcohol may protect against RA. This highlights the potential role of lifestyle in determining the risk of developing RA, and emphasises the advice to stop smoking, but not necessarily to abstain from alcohol in order to diminish risk of RA. The evidence of potential RA prevention should prompt additional studies on how this can be achieved.

Markers of the early stage of rheumatoid arthritis

2016 ◽  
Vol 51 (4) ◽  
pp. 305-314
Author(s):  
Beata Polińska ◽  
Joanna Matowicka-Karna ◽  
Halina Kemona
Keyword(s):  
Rheumatoid Arthritis ◽  
Human Population ◽  
Early Stage ◽  
Clinical Signs ◽  
High Sensitivity ◽  
Unknown Etiology ◽  
Serological Tests ◽  
Citrullinated Peptide ◽  
Peptide Antibodies

Rheumatoid arthritis (RA) is a chronic, autoimmune connective tissue disease of unknown etiology. RA affects about 1% of the human population, women suffer three times more often than men, with the peak incidence between the age of 40 to 50. The up-to-date criteria from 2010 for the diagnosis of RA include: occurrence and duration of clinical signs, indicators of inflammation and serological tests. Neopterin, a protein released by macrophages, is a sensitive indicator of inflammation and the severity of RA. Regarding the serological tests, anti-cyclic citrullinated peptide antibodies represent a well-known marker with the specificity for RA of about 98%. The antibodies may be present in the serum of patients even a few years before the first clinical signs of the disease, heralding erosive changes in the joints and more severe course of RA. The literature also contains reports about autoantibodies anti-CarP and anti-Sa/ anti-MCV, which may occur in people with pain and swelling of joints and precede full-blown development of RA as well as reflect disease activity. Serological diagnosis of RA may be supported by some genetic tests based on PCR for detecting mutations e.g. C1858T in the PNPN22 gene. In turn, the quantitative analysis of different classes of miRNAs seems justified in order to better classify patients showing symptoms of RA. Further studies are needed that take into account the role of different markers in the development of RA, and confirm the high sensitivity and specificity of these markers in the diagnosis of the disease.

scholarly journals The role of HLA typing in rheumatic diseases

2020 ◽  
Vol 3 (1) ◽  
pp. 1-8
Author(s):  
Luca Mascaretti ◽  
Elena Bevilacqua
Keyword(s):  
Rheumatoid Arthritis ◽  
Juvenile Idiopathic Arthritis ◽  
Amino Acid ◽  
Ankylosing Spondylitis ◽  
Hla Class I ◽  
Acid Sites ◽  
Hla Typing ◽  
Erosive Disease ◽  
Complex Cases

Association between HLA-DR4 and rheumatoid arthritis (RA) has been known for 4 decades, and amino acid sites within HLA-DRB1 (11/13, 71, 74) are highly associated with RA. HLA is not useful for diagnosis or prognosis, but it may help predict severe and erosive disease. Since 90% of patients with ankylosing spondylitis (AS) and 50-70% of other spondyloarthritis (SpA) patients are HLA-B*27 positive, HLA is a stronghold of diagnostic algorithms. Genetic predisposition to juvenile idiopathic arthritis (JIA) is mainly due to HLA class II, and to a lesser extent to HLA class I. Although HLA plays a role in rheumatic disorders, its clinical relevance is not homogeneous. When classical biomarkers are lacking or in complex cases, HLA typing may provide support for the management of patients.

scholarly journals Peptides Bearing Multiple Post-Translational Modifications as Antigenic Targets for Severe Rheumatoid Arthritis Patients

2021 ◽  
Vol 22 (24) ◽  
pp. 13290
Author(s):  
Cristina García-Moreno ◽  
María J. Gómara ◽  
Raúl Castellanos-Moreira ◽  
Raimon Sanmartí ◽  
Isabel Haro
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Serum Antibody ◽  
Joint Damage ◽  
Erosive Disease ◽  
Post Translational Modifications ◽  
Diagnosis And Prognosis ◽  
Modified Peptides ◽  
Chimeric Peptides

Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies that are of paramount importance for the diagnosis and prognosis of the disease and have been implicated in its pathogenesis. Proteins resulting from post-translational modifications (PTMs) are capable of triggering autoimmune responses important for the development of RA. In this work, we investigate serum antibody reactivity in patients with an established RA against a panel of chimeric peptides derived from fibrin and filaggrin proteins and bearing from one to three PTMs (citrullination, carbamylation and acetylation) by home-designed ELISA tests (anti-AMPA autoantibodies). The role of anti-AMPAs as biomarkers linked to the presence of a more severe RA phenotype (erosive disease with radiological structural damage) and to the presence of interstitial lung disease (ILD), a severe extra-articular manifestation in RA patients entailing a high mortality, was also analyzed. In general, the association with the clinical phenotype of RA was confirmed with the different autoantibodies, and especially for IgA and IgM isotypes. The prevalence of severe joint damage was only statistically significant for the IgG isotype when working with the peptide bearing three PTMs. Furthermore, the median titers were significantly higher in patients with RA-ILD, a finding not observed for the IgG isotype when working with the single- and double-modified peptides.

Hierarchy in the Avidity and Cross-reactivity of Anti-citrullinated Protein Antibodies in the Serum of Patients With Rheumatoid Arthritis

2020 ◽  
Author(s):  
Akihisa Haraguchi ◽  
Hisakata Yamada ◽  
Takahide Sakuragi ◽  
Tomomi Tsuru ◽  
Masakazu Kondo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Response ◽  
Serum Antibody ◽  
Cross Reactivity ◽  
Sodium Thiocyanate ◽  
Fine Specificity ◽  
Thiocyanate Solution ◽  
Citrullinated Protein ◽  
Citrullinated Peptide ◽  
Substantial Extent

Abstract BackgroundFine specificity of anti-citrullinated protein antibodies (ACPAs), in which cross-reactivity exists, varies among patients with rheumatoid arthritis (RA), but it is unclear whether the mechanism of ACPA production is same or different among individuals. Since avidity of serum antibody reflects the direction of immune response, we compared the levels of avidity and cross-reactivity between various ACPAs in a cohort of RA patient.MethodsSera from 180 RA patients positive for anti-cyclic citrullinated peptide (CCP) 2 antibody were screened for positivity of antibodies against CCP1, and citrullnated fibrinogen (cFib), enolase (cEno), and vimentin (cVim) peptides. Avidity of the four ACPAs, and some autoantibodies and antibodies against foreign antigens was determined by an elution assay using sodium thiocyanate solution. Cross-reactivity between different ACPAs was estimated by measuring the inhibition of binding by competitor peptides. ResultsThe prevalence of anti-CCP1, anti-cFib, anti-cEno, and anti-cVim antibodies in the anti-CCP2-positive RA cohort were 37.7%, 38.3%, 15.6%, and 23.9%, respectively. The avidity of ACPAs, except for anti-cVim antibody, was significantly lower than that of antibodies against foreign antigens, while there was a large variety in the avidity of other autoantibodies. At individual levels, the avidity of anti-cVim was significantly higher than that of other ACPAs, and there was a significant correlation in the avidity of anti-CCP and anti-cFib antibodies. Substantial extent of cross-reactivity was seen between different ACPAs, which also showed a fixed hierarchy.ConclusionThe fixed hierarchy in the avidity and cross-reactivity between different ACPAs suggests that the mechanism underlying ACPA production is common to all RA patients. Presence of a dominant antigen that induces whole ACPA response is speculated.

scholarly journals Periodontitis and Rheumatoid Arthritis: The Same Inflammatory Mediators?

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Fulvia Ceccarelli ◽  
Matteo Saccucci ◽  
Gabriele Di Carlo ◽  
Ramona Lucchetti ◽  
Andrea Pilloni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Proinflammatory Cytokines ◽  
Healthy Subjects ◽  
Structural Damage ◽  
Genetic Factors ◽  
The Many ◽  
Citrullinated Peptide ◽  
Anticyclic Citrullinated Peptide Antibodies ◽  
Peptide Antibodies

The strict link between periodontitis (PD) and rheumatoid arthritis (RA) has been widely demonstrated by several studies. PD is significantly more frequent in RA patients in comparison with healthy subjects: this prevalence is higher in individuals at the earliest stages of disease and in seropositive patients. This is probably related to the role of P. gingivalis in inducing citrullination and leading to the development of the new antigens. Despite the many studies conducted on this topic, there is very little data available concerning the possibility to use the same biomarkers to evaluate both RA and PD patients. The aim of the review is to summarize this issue. Starting from genetic factors, data from literature demonstrated the association between HLA-DRB1 alleles and PD susceptibility, similar to RA patients; moreover, SE-positive patients showed simultaneously structural damage to the wrist and periodontal sites. Contrasting results are available concerning other genetic polymorphisms. Moreover, the possible role of proinflammatory cytokines, such as TNF and IL6 and autoantibodies, specifically anticyclic citrullinated peptide antibodies, has been examined, suggesting the need to perform further studies to better define this issue.

The Role of Novel Bone Forming Agents in the Treatment of Osteoporosis

2020 ◽  
pp. 089719002096122
Author(s):  
Hansita B. Patel ◽  
Lynsie J. Lyerly ◽  
Cheryl K. Horlen
Keyword(s):  
Elderly Population ◽  
Cost Effective ◽  
The Elderly ◽  
Bisphosphonate Therapy ◽  
Evidence Based ◽  
First Line ◽  
Treatment Of Osteoporosis ◽  
Cost Effective Treatment

Osteoporosis is a growing epidemic that leads to significant morbidity and mortality among the elderly population due to associated fractures that lead to disabilities and reduced quality of life. Bisphosphonates are well-established as a first-line and cost-effective treatment for osteoporosis. Unfortunately, clinicians are often uncertain as to how to select treatments when bisphosphonates are ineffective as initial treatment or contraindicated. Romosozumab and abaloparatide are 2 alternative agents that have been recently FDA approved for the treatment of osteoporosis in postmenopausal women at high risk for fracture or patients who have failed or are intolerant to other osteoporosis therapies. Currently, the National Osteoporosis Foundation (NOF) has no formal recommendations in regard to these 2 novel agents. The purpose of this review is to help guide pharmacists on how to ensure appropriate utilization of these 2 novel bone-forming agents as potential alternatives to bisphosphonate therapy by providing evidence-based recommendations according to the current literature and key counseling points.

scholarly journals Association between interleukin-21 gene rs6822844 polymorphism and rheumatoid arthritis susceptibility

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Kewei Ren ◽  
Jilei Tang ◽  
Luming Nong ◽  
Nan Shen ◽  
Xiaolong Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Publication Bias ◽  
Genetic Model ◽  
Meta Analysis ◽  
Case Control Studies ◽  
Pubmed Database ◽  
Dominant Genetic Model ◽  
Stratified Analysis ◽  
Acpa Status ◽  
Citrullinated Protein

Abstract Controversial results concerning the association between a polymorphism rs6822844 in the interleukin (IL) 21 (IL-21) gene and rheumatoid arthritis (RA) have existed. A meta-analysis to confirm above relationships is necessary to be performed immediately. We conducted a search in the PubMed database, covering all papers published up to 20 October 2018. Overall, six case–control studies with 3244 cases and 3431 healthy controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed with both Egger’s and Begg’s tests. After calculation, we found that IL-21 rs6822844 polymorphism could decrease RA risk in overall genetic models (allelic contrast: OR = 0.77, 95% CI = 0.62–0.97, P=0.024; TG versus GG: OR = 0.68, 95% CI = 0.50–0.92, P=0.013, and dominant genetic model: OR = 0.72, 95% CI = 0.55–0.94, P=0.016). Similarly, stratified analysis by race, source of control, significantly decreased association was found in Asians, Caucasians and hospital-based (HB) control source. Finally, in the subgroup analysis of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status, poorly decreased relationship was detected between IL-21 rs6822844 polymorphism and RF negative and ACPA positive RA risk, respectively. No obvious evidence of publication bias was detected in overall analysis. In summary, our study indicated that IL-21 rs6822844 polymorphism was significantly associated with decreased RA susceptibility.

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