scholarly journals Anti-carbamylated Protein Antibodies Are Present Prior to Rheumatoid Arthritis and Are Associated with Its Future Diagnosis

2015 ◽  
Vol 42 (4) ◽  
pp. 572-579 ◽  
Author(s):  
Ryan W. Gan ◽  
Leendert A. Trouw ◽  
Jing Shi ◽  
René E.M. Toes ◽  
Tom W.J. Huizinga ◽  
...  

Objective.Anti-carbamylated protein (anti-CarP) antibodies could further elucidate early rheumatoid arthritis (RA) pathogenesis and predict clinical disease. We compared the diagnostic accuracy of anti-CarP antibodies for future RA to other RA-related antibodies in military personnel.Methods.Stored pre-RA diagnosis serum samples from 76 RA cases were tested for anti-CarP fetal calf serum (FCS), anti-CarP fibrinogen (Fib), anticyclic citrullinated peptide antibodies version 2 (anti-CCP2), rheumatoid factor-nephelometry (RF-Neph), and RF isotypes [immunoglobulin M (IgM), IgG, and IgA]. Positivity for all antibodies was determined as ≥ 2 SD of log-transformed means from controls. Relationships between autoantibodies and future RA were assessed in prediagnosis serum for all RA cases compared to controls using sensitivity, specificity, and logistic regression. Differences in diagnostic accuracy between antibody combinations were assessed using comparisons of area under the curves (AUC).Results.Anti-CarP-FCS was 26% sensitive and 95% specific for future RA, whereas anti-CarP-Fib was 16% sensitive and 95% specific for future RA. Anti-CarP-FCS positivity was associated with future RA, while anti-CarP-Fib trended toward association. The antibody combination of anti-CCP2 and/or ≥ 2 RF (RF-Neph and/or RF-isotypes) resulted in an AUC of 0.72 for future RA, where the AUC was 0.71 with the addition of anti-CarP-FCS to this prior combination.Conclusion.Adding anti-CarP-FCS to antibody combinations did not improve AUC. However, anti-CarP-FCS was associated with future onset of RA, and was present in prediagnosis serum in ∼10% of RA cases negative for anti-CCP2 but positive for RF.

2021 ◽  
Author(s):  
Ula von Mentzer ◽  
Tilia Selldén ◽  
LOISE Råberg ◽  
Gizem Erensoy ◽  
Anna-Karin Hultgård-Ekwall ◽  
...  

<div>Intra-articular drug delivery strategies aiming to deliver drugs in diseases affected by cartilage-related issues are using electrostatic interactions to penetrate the dense cartilage matrix. This enables delivery of sufficient drug concentrations to the chondrocytes to mediate the desired therapeutic effect. As it is well known that size and charge of nanoparticles affects its interactions with the surrounding biological fluids, where proteins adsorb to the NP surface, resulting in a protein corona. There are, however, no studies investigating how the formed protein coronas affect cartilage uptake and subsequent cellular uptake, nor how they affect other cells present in the synovium of such diseases. Here, we explore the differences between the protein coronas that form when NP are incubated in synovial fluid from osteoarthritic and rheumatoid arthritis patients and compare this to results obtained using fetal calf serum (FCS), as guide for researchers working on joint drug delivery. We demonstrate that the protein corona indeed affects the uptake into cartilage, where there are major differences between the model proteins in fetal calf serum, as compared to synovial fluid from rheumatoid arthritis patients as well as osteoarthritis patients. The data suggests that when developing drug delivery vehicles for joint diseases that leverages electrostatic interactions and size, the interactions with proteins in the biological milieu is highly relevant to consider.</div>


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Fulvia Ceccarelli ◽  
Matteo Saccucci ◽  
Gabriele Di Carlo ◽  
Ramona Lucchetti ◽  
Andrea Pilloni ◽  
...  

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.


2017 ◽  
Vol 44 (9) ◽  
pp. 1325-1330 ◽  
Author(s):  
Mike L.T. Berendsen ◽  
Marissa C. van Maaren ◽  
Elke E.A. Arts ◽  
Alfons A. den Broeder ◽  
Calin D. Popa ◽  
...  

Objective.To determine whether anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) are risk factors for 10-year cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA).Methods.Analyses were performed using data from the Nijmegen early RA inception cohort, in which patients with newly diagnosed RA, consecutively included since 1985, were regularly followed up. Anti-CCP and RF were determined at baseline (diagnosis). Outcome was the first cardiovascular disease (CVD) event [ischemic heart disease, nonhemorrhagic cerebrovascular accident (CVA), or peripheral artery disease (PAD)] after baseline as retrieved from physician diagnosis. Fatality was checked against death certificates. Cox regression including correction for baseline confounders was performed to estimate the effect of anti-CCP, RF, and their interaction on 10-year CVD-free survival.Results.Of 929 patients included, 628 were anti-CCP–positive and 697 were RF-positive. During followup, with a median of 7.5 years, 162 CV events were observed (101 ischemic heart disease, 45 CVA, and 16 PAD), of which 15 were fatal. The HRadjusted for anti-CCP was 1.17 (95% CI 0.82–1.67) and the HRadjusted for RF was 1.52 (95% CI 1.00–2.30). The association of RF positivity with CVD was even stronger in the anti-CCP–negative patients: HRadjusted 2.09 (95% CI 1.18–3.71). There was no significant interaction (p = 0.098) between anti-CCP and RF.Conclusion.Rather than anti-CCP, presence of RF was associated with CVD in this cohort of patients with RA.


2020 ◽  
Vol 12 ◽  
pp. 1759720X2097813
Author(s):  
Raul Castellanos-Moreira ◽  
Sebastian C. Rodriguez-Garcia ◽  
Sonia Cabrera-Villalba ◽  
María José Gomara ◽  
Georgina Salvador ◽  
...  

Background: A restricted response against citrullinated peptides/proteins, with less isotype usage, has been found in palindromic rheumatism (PR) in comparison with rheumatoid arthritis (RA). We hypothesized that this different antibody response may be observed for other post-translational modified proteins. We compared the prevalence and isotype usage of two specificities of anti-carbamylated peptide/protein antibodies (Anti-CarP) in patients with PR and RA. Methods: Cross-sectional study including 54 patients with pure PR and 53 patients with RA, matched by sex, age, disease duration and ACPA. Anti-CarP specificities were determined by home-made enzyme-linked immunosorbent assay tests using a synthetic chimeric fibrin/filaggrin homocitrullinated peptide (CFFHP) and fetal calf serum (FCS) homocitrullinated protein as antigens. IgG, IgA and IgM isotypes were measured. Results: Anti-CarP were positive (CFFHP or FCS) in 24% and 64% of patients with PR and RA, respectively ( p < 0.005). All Anti-CarP isotype proportions were significantly lower in PR than in RA: Anti-CarP-IgG (24% versus 51%), Anti-CarP-IgA (7% versus 34%) and Anti-CarP-IgM (7% versus 36%). Mean titers of Anti-CarP isotypes were also lower in PR. In Anti-CarP positive patients, the isotype distribution differed between PR and RA: IgG Anti-CarP was used in all PR patients and in 79% of RA patients. By contrast, a significantly lower isotype usage of both IgA (31% versus 53%) and IgM (31% versus 56%) was observed in PR patients. No significant differences in clinical or demographic characteristics were observed according to Anti-CarP status in PR patients, except for a higher prevalence of ACPA and higher mean titers of ACPA and rheumatoid factor in Anti-CarP positive patients. Conclusion: Anti-CarP are found in patients with PR but in a lower proportion and with a different isotype usage from in RA, suggesting a distinct B cell response to homocitrullinated antigens in PR.


2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Yoshiaki Kinoshita ◽  
Atsuhiko Sakamoto ◽  
Kouko Hidaka

Rheumatoid arthritis patients are susceptible to interstitial lung disease, and joint manifestations of rheumatoid arthritis usually precede lung involvements by several years. Organizing pneumonia, as the first manifestation of rheumatoid arthritis, is extremely rare, and its clinical features remain currently unknown. We present a case and a literature review of patients who were pathologically diagnosed with organizing pneumonia first and met the diagnostic criteria of rheumatoid arthritis later. In this review, we observed the following: (1) patients with organizing pneumonia preceding rheumatoid arthritis have a high prevalence of rheumatoid factor or anticyclic citrullinated peptide antibodies; (2) almost all patients developed rheumatoid arthritis within one year after the diagnosis of organizing pneumonia. We suggest that patients with organizing pneumonia and positive for either rheumatoid factor or anticyclic citrullinated peptide antibody should be cautiously followed up regarding the development of rheumatoid arthritis, particularly during the first year after the diagnosis of organizing pneumonia.


2007 ◽  
Vol 2 (3) ◽  
pp. S28
Author(s):  
N Vasanthy ◽  
J Sasikala ◽  
RC Panchapakesa ◽  
R Ravichandran ◽  
S Rukmangatharajan ◽  
...  

2019 ◽  
Vol 46 (7) ◽  
pp. 670-675 ◽  
Author(s):  
Kristina Forslind ◽  
Kerstin Eberhardt ◽  
Björn Svensson

Objective.The aim of this study was to examine the occurrence of repair in a cohort of conventionally treated patients with early rheumatoid arthritis over 8 years.Methods.There were 395 patients included in the BARFOT study having radiographs of hands and feet at inclusion, and at 1, 2, 5, and 8 years, which were chronologically scored for erosions by the Sharp/van der Heijde method. An erosion with repair was defined as an erosion that has become partially or totally filled, with or without sclerosis.Results.Erosions with repair were observed in 64 patients (16%) at 1 year, 113 (29%) at 2 years, 142 (36%) at 5 years, and 200 (51%) at 8 years. At the 1-year visit, 13% of the patients with at least 1 new erosion showed repair versus 3% of the patients with no new erosions (p = 0.001). At 2, 5, and 8 years the corresponding figures were 22% and 6%, 28% and 8%, and 39% and 11%, respectively (all p = 0.001). The sum of all repaired erosions correlated strongly with the sum of all erosions and with the sum of all erosion scores (ρ = 0.79 and 0.77). Presence of rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) was significantly associated with both new erosions and repair.Conclusion.Repair was more common than previously described. The frequency of repair increased over time and was associated with the number of erosions. RF- and anti-CCP–positivity, patient age, and presence of erosions at baseline were independent predictors of repair.


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