Figure 1 - uploaded by Björn Svensson
Content may be subject to copyright.
Health Assessment Questionnaire (HAQ) scores during the disease course according to presence of anticarbamylated protein (anti-CarP) antibodies in patients with rheumatoid arthritis (RA) from the (A) Better Anti-Rheumatic PharmacOTherapy (BARFOT) and (B) Leiden Early Arthritis Clinic (EAC) cohorts. Presented are observed mean HAQ scores assessed in (A) 784 patients with RA over 8 years from the BARFOT cohort and in (B) 820 patients with RA over 5 years from the Leiden EAC cohort.
Source publication
Clinically relevant joint destruction has now become infrequent in patients with newly diagnosed rheumatoid arthritis (RA), while other disease outcomes such as functional ability and disease persistence have become more important. Recently, novel auto-antibody reactivities have been identified in RA, with the ultimate aim to better characterise pa...
Contexts in source publication
Context 1
... the patients with RA, 36% and 46% were positive for anti-CarP antibodies in the BARFOT and Leiden EAC cohorts, respectively (table 1). Univariate analysis within the BARFOT cohort showed that anti-CarP positivity was significantly associated with functional disability; patients carrying anti-CarP antibodies had 0.082 (95% CI 0.0064 to 0.16, p value 0.034) higher HAQ scores during the 8 years of follow-up compared with patients without anti-CarP antibodies ( figure 1A). In the model including all three auto-antibodies, anti-CarP was not significantly associated with HAQ over time: effect size of anti-CarP 0.053, 95% CI −0.039 to 0.15, p value 0.26. ...
Context 2
... ACPA and RF did not associate with HAQ over time independent of the other auto-antibodies ( p values, respectively, 0.29 and 0.94). Within the Leiden EAC, anti-CarP was not associated with functional ability during 5 years of disease: effect size 0.026, 95% CI −0.053 to 0.10, p value 0.52; after additional adjustment for ACPA and RF, the effect size of the association was 0.0051, 95% CI −0.094 to 0.10, p value 0.92 ( figure 1B). ...
Similar publications
Objective(s)
This study evaluated the interaction of anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) in predicting sustained clinical response in an observational registry of patients with rheumatoid arthritis (RA) followed in routine practice.
Methods
Patients with RA enrolled in the Ontario Best Practices Research Initiative...
Citations
... Most previous studies, although of high quality and large sample size, were limited to DAS28-ESR or HAQ as the only measures of disease activity 18,22,23 . All these studies detected a significant increase in DAS28-ESR associated with the presence of ACarPA at the first visit 18,22,24 . ...
... In one of the cohorts, the HAQ increase was observed both in the first visit and in the overall period of follow-up independently of the presence of anti-CCP 22 . In the other study, the increase was observed only in one of the two cohorts and this association disappeared in the analysis including RF and anti-CCP 23 . Our results fit in this background because the increase in HAQ was only clear at the first visit and disappeared thereafter. ...
The initial management of rheumatoid arthritis (RA) has a high impact on disease prognosis. Therefore, we need to select the most appropriate treatment as soon as possible. This goal requires biomarkers of disease severity and prognosis. One such biomarker may be the presence of anti-carbamylated protein antibodies (ACarPA) because it is associated with adverse long term outcomes as radiographic damage and mortality. Here, we have assessed the ACarPA as short-term prognostic biomarkers. The study was conducted in 978 prospective early arthritis (EA) patients that were followed for two years. Our results show the association of ACarPA with increased levels of all the disease activity measures in the first visit after arthritis onset. However, the associations were more significant with the high levels in local measures of inflammation and physician assessment than with the increases in systemic inflammation and patient-reported outcomes. More notably, disease activity was persistently increased in the ACarPA positive patients during the two years of follow-up. These differences were significant even after accounting for the presence of other RA autoantibodies. Therefore, the ACarPA could be considered short-term prognostic biomarkers of increased disease activity in the EA patients.
... Another promising usage is the discrimination of patients with a poor prognosis. Anti-CarP Ab is a risk factor for future joint destruction independent of ACPA [1,[33][34][35][36][37]. A previous study reported that the anti-carbamylated albumin antibody was associated with a history of cardiovascular disease (CVD) [15] and anti-CarP Ab was associated with multiple indices of arteriosclerosis [38]. ...
Several autoantibodies against proteins with post-translational modifications have been detected in patients with rheumatoid arthritis (RA) and are called anti-modified protein antibodies (AMPAs). Anti-carbamylated protein antibodies (Anti-CarP Ab) are the second most vigorously researched AMPAs following anti-citrullinated protein/peptide antibodies (ACPA). Anti-CarP Ab and ACPA show cross-reactivity to some extent and frequently co-exist with each other in RA, but are two distinct antibodies. Although the diagnostic efficacy of anti-CarP Ab is inferior to that of ACPA, the diagnostic specificity of RA may improve when used in combination with ACPA and rheumatoid factor. Anti-CarP Ab and ACPA are also useful for identifying patients at high risk of more severe joint destruction and cardiovascular diseases. The high prevalence of the co-existence of both antibodies suggests a common factor in their production, and this is important for the development of RA because both antibodies emerge before the onset of clinical symptoms. Neutrophils may also be crucially involved. It is important to distinguish citrullinated antigens from carbamylated antigens because the methods commonly used to detect the former are now known to be cross-reactive with the latter. Research on anti-CarP Ab will provide novel insights into the pathology and etiology of RA.
... Within the RA population, patients can display a mild or a more severe disease course, with differences in clinical disease activity or in radiological progression, or both. Whether the presence of antiCarP antibodies at baseline is associated with increased 28joint dis ease activity score 103 is currently uncertain as one study observed a correlation 94 and another study did not 104 . It is wellestablished that ACPApositive patients display on average moresevere joint damage as compared with the ACPAnegative group 87 . ...
The presence of autoantibodies is one of the hallmarks of rheumatoid arthritis (RA). In the past few decades, rheumatoid factors (autoantibodies that recognize the Fc-tail of immunoglobulins) as well as anti-citrullinated protein antibodies (ACPAs) have been studied intensively. ACPAs recognize post-translationally modified proteins in which the amino acid arginine has been converted into a citrulline. More recently, other autoantibody systems recognizing post-translationally modified proteins have also gained attention, including autoantibodies recognizing fragmented immunoglobulin (anti-hinge antibodies), autoantibodies recognizing acetylated proteins and autoantibodies recognizing proteins that are modified by adducts formed under oxidative stress. In particular, detailed insights have been obtained on the presence and properties of autoantibodies recognizing carbamylated proteins, commonly called anti-carbamylated protein (anti-CarP) antibodies. In this Review, we summarize the current knowledge relating to these emerging autoantibodies that recognize post-translationally modified proteins identified in RA, with an emphasis on anti-CarP antibodies.
... We thank Ajeganova et al 1 for the interesting comments on our paper 2 , and note the different findings compared with our results. 1 2 We would suggest a potential explanation for this lies within the different patient populations. Although inclusion criteria for the Swedish Better Anti-Rheumatic PharmacOTherapy (BARFOT) cohort and Leiden Early arthritis Clinic (EAC) are not detailed, we are aware from previous publications that inclusion criteria to these cohorts require patients to satisfy the 1987 American College of Rheumatology (ACR) classification criteria for rheumatoid arthritis (RA) at baseline and within 1 year of symptom onset, respectively. ...
We thank Ajeganova et al 1 for the interesting comments on our paper2, and note the different findings compared with our results.1 ,2 We would suggest a potential explanation for this lies within the different patient populations. Although inclusion criteria for the Swedish Better Anti-Rheumatic PharmacOTherapy (BARFOT) cohort and Leiden Early arthritis Clinic (EAC) are not detailed, we are aware from previous publications that inclusion criteria to these cohorts require patients to satisfy the 1987 American College of Rheumatology (ACR) classification criteria for rheumatoid arthritis (RA) at baseline and within 1 year of symptom onset, respectively.3 , …
Purpose of review:
This article provides an overview of the recent findings present in the field of antimodified protein antibodies and their relevance for rheumatic disease, with a focus on rheumatoid arthritis.
Recent findings:
Next to anticitrullinated protein antibodies, also other antimodified protein antibodies such as anticarbamylated protein antibodies or antiacetylated protein antibodies are emerging. Likewise, their possible pathological contributions are getting detailed attention. Their possible relation to disease, both from a clinical as well as biological perspective will be summarized.
Summary:
Current evidence is pointing to the notion that especially a combination of antimodified protein antibodies associates best with clinical phenotype and outcome.
