Diagnostic value of anti-citrullinated α-enolase peptide 1 antibody in patients with rheumatoid arthritis: A systematic review and meta-analysis

Abstract

Aim: To evaluate the diagnostic value of anti-citrullinated α-enolase peptide 1 (anti-CEP 1) antibody in patients with rheumatoid arthritis (RA) by conducting a systematic review and meta-analysis.

Methods: The PubMed, Web of Science, Embase, Scopus, and Cochrane Library databases were searched for relevant studies published until September 23, 2020. A bivariate mixed-effects model was used to calculate the diagnostic indices from primary data of eligible studies. We performed meta-regression and subgroup analysis to explore the sources of heterogeneity.

Results: Twenty-four articles, with a total of 17 380 patients with RA and 7505 control participants, met the criteria for inclusion in the meta-analysis. The pooled sensitivity, specificity, and positive and negative likelihood ratios for the anti-CEP 1 antibody were 44% (95% CI: 38%-51%), 97% (95% CI: 96%-98%), and 14.81 (95% CI: 10.66-20.57) and 0.57 (95% CI: 0.52-0.64), respectively. The pooled positive and negative predictive values were 0.96 (95% CI: 0.95-0.97) and 0.53 (95% CI: 0.43-0.63), respectively. The area under the summary receiver operating characteristic curve was 0.86. Meta-regression indicated that the anti-CEP 1 antibody detection method may be a source of heterogeneity. The subgroup analysis of the group in which the anti-CEP 1 antibody was detected by using a commercial enzyme-linked immunosorbent assay (ELISA) kit had a sensitivity of 59% (95% CI: 50%-68%) and a specificity of 93% (95% CI: 85%-97%).

Conclusions: The anti-CEP 1 antibody had moderate RA diagnostic value with relatively low sensitivity and high specificity. An ELISA may increase the RA diagnostic sensitivity.

Keywords: anti-citrullinated protein antibodies; anti-citrullinated α-enolase peptide 1 antibody; autoantibody; diagnosis; meta-analysis; rheumatoid arthritis.

FIGURE 1

Flow diagram for screening studies and results

FIGURE 2

Literature quality assessment by using the Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool for eligible studies

FIGURE 3

Forest plots and summary receiver operating characteristic curves of the anti‐citrullinated α‐enolase peptide 1 (anti‐CEP 1) for rheumatoid arthritis (RA). (A) Sensitivity forest plot; (B) specificity forest plot; (C) summary receiver operating characteristic curve

FIGURE 4

Univariable meta‐regression and subgroup analysis of 3 covariates (control group, diagnostic criteria for rheumatoid arthritis (RA), method for detection of the anti‐citrullinated α‐enolase peptide 1 [anti‐CEP 1] antibody)