Meta-Analysis: Diagnostic Accuracy of Anti-Carbamylated Protein Antibody for Rheumatoid Arthritis
July
Meta-Analysis: Diagnostic Accuracy of Anti-Carbamylated Protein Antibody for Rheumatoid Arthritis
Liubing Li 0 1 2
Chuiwen Deng 0 1 2
Si Chen 0 1 2
Shulan Zhang 0 1 2
Ziyan Wu 0 1 2
Chaojun Hu 0 1 2
Fengchun Zhang 0 1 2
Yongzhe Li 0 1 2
0 Funding: This research was funded by Research Special Fund for Public Welfare Industry of Health (NO. 201202004; FCZ); National Natural Science Foundation of China (NO. 81172857, 81373188, 81302591
1 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing , China , 2 Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University , Beijing , China
2 Editor: Michael Nurmohamed, VU University Medical Center , NETHERLANDS
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Data Availability Statement: All relevant data are
within the paper and its Supporting Information files.
Objective
Methods
The anti-carbamylated protein (CarP) antibody is a novel biomarker that might help in the diagnosis of rheumatoid arthritis (RA). We aim to assess the diagnostic value of anti-CarP antibody for RA.
We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and
Scopus for studies published by December 15, 2015. Studies in any language that evalu
ated the utility of the anti-CarP antibody in the diagnosis of RA in which healthy donors or
patients without arthritis or arthralgia served as controls were included. Two investigators
independently evaluated studies for inclusion, assessed study quality and abstracted data.
A bivariate mixed-effects model was used to summarize the diagnostic indexes from 7 eligible studies.
Results
The pooled sensitivity, specificity, and positive and negative likelihood ratios for anti-CarP
antibody were 42% (95% CI, 38% to 45%), 96% (95% CI, 95% to 97%), 10.2 (95% CI, 7.5
to 13.9), and 0.61 (95% CI, 0.57 to 0.65), respectively. The summary diagnostic odds ratio
was 17 (95% CI, 12 to 24), and the area under summary receiver operator characteristic
curve was 80% (95% CI, 77% to 84%).
Conclusion
Anti-CarP antibody has a moderate value in the diagnosis of RA with high specificity but relatively low sensitivity.
www.most.gov.cn/eng/; YZL); Capital Health
Research and Development of Special Fund (NO.
2014-1-4011; YZL). The funders had no role in study
design, data collection and analysis, decision to
publish, or preparation of the manuscript.
Introduction
Rheumatoid arthritis (RA) is a common systemic autoimmune disease, characterized by
persistent synovitis, systemic inflammation, and the presence of autoantibodies, particularly anti–
cyclic citrullinated peptide (CCP) antibody and rheumatoid factor (RF). RA affects
approximately 1% of the population globally[
1
], and 0.5–1.0% of the adult population in developed
countries [
2
]. The disorder is more prevalent among women older than 65 years. For the
development of RA, 50% of the risk is attributable to genetic factors, and the main environmental
risk factor is smoking [
2
].
Irreversible damage to the joints is observed in RA; however early prevention is possible
through early diagnosis and treatment. Currently, the anti-CCP antibody and RF are a part of
the 2010 American College of Rheumatology (ACR)/The European League Against
Rheumatism (EULAR) classification criteria for RA [
3, 4
]. Despite the diagnostic contribution of the
anti-CCP antibody and RF, approximately one-third of patients with RA remain seronegative
[5]. Novel serological biomarkers are strongly needed to further improve the diagnosis of
seronegative RA.
Anti-carbamylated protein (CarP) antibody, a novel autoantibody, has been detected in RA
patients and predicts the development of the pathogenesis of RA, independent of the anti-CCP
antibody [
6, 7
]. This antibody recognizes proteins post-translationally modified by a process of
carbamylation, rather than citrullination [8]. Carbamylation occurs when cyanate binds to
primary amino or thiol groups presented in the body in equilibrium with urea [
8, 9
]. The
antiCarP antibody has been described in RA, especially in anti-CCP-negative patients [
10, 11
].
However, there are controversies regarding the diagnostic accuracy of the anti-CarP antibody
in the literature. In this meta-analysis, published data on the sensitivity, specificity, and
likelihood ratios of the anti-CarP antibody were summarized for the diagnosis of RA.
Methods
Data sources and searches
Without language restrictions, we searched PubMed, Embase, the Cochrane Library, Web of
science, and Scopus for studies published by December 15, 2015 that detected the anti-CarP
antibody. Our search combined the following index terms: autoantibody to carbamylated
protein, autoantibody to CarP, anti-carbamylated protein antibody, anti-CarP antibody,
rheumatoid arthritis, RA. The details of the search strategy are list (...truncated)