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

Abstract

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.

Anti-Citrullinated Cyclic Peptide Antibody and Functional Disability Are Associated With Poor Sleep Quality in Rheumatoid Arthritis

“…26 Studies have consistently pointed out the role of this antibody as a strong predictor of joint erosions in RA. 27 RA patients who test positive for anti-CCP antibody are more prone to develop progressive joint damage. 28 The severity of joint damage tends to parallel the degree of functional reported that Moroccan RA patients who were anti-CCP positive had higher HAQ scores.…”

Association between -174G/C and -572G/C interleukin 6 gene polymorphisms and severe radiographic damage to the hands of Mexican patients with rheumatoid arthritis: a preliminary report

“…Interestingly, the -572G/G polymorphism was associated with the presence of positivity for antiCCPs, but not with joint damage severity according to the Steinbrocker's scale. The authors of several studies have reported an association between the presence of anti-CCPs and higher radiological damage (Marinou et al, 2007;Jilani and Mackworth-Young, 2015). A meta-analysis conducted by Jilani and Mackworth-Young (2015) clearly identifies that ACPAs (anti-CCP and anti-MCV) are associated with the severity of the joint damage.…”

Problems of Rheumatoid Arthritis Immunopathology: Evolution of the Disease

“…Следует напомнить, что IgM РФ и АЦЦП явля-ются основными лабораторными диагностическими мар-керами РА, включенными в классификационные крите-рии РА (ACR/EULAR, 2010) [17]. Гиперпродукция АЦЦП (особенно в комбинации с РФ) ассоциируется с активно-стью заболевания, прогрессированием деструкции суста-вов [8,13,18], развитием экстраартикулярных (систем-ных) проявлений [13], риском общей летальности, свя-П р о г р е с с в р е в м а т о л о г и и в X X I в е к е Рис. 1.…”