A comparison of a fluorescence enzyme immunoassay versus indirect immunofluorescence for initial screening of connective tissue diseases: Systematic literature review and meta-analysis of diagnostic test accuracy studies

The aim was to compare indirect immunofluorescence (IIF) and fluorescence enzyme immunoassay (FEIA) for initial screening of connective tissue diseases (CTDs) and to evaluate whether combining IIF with FEIA adds value. A comprehensive systematic literature review was conducted to identify fully paired, cross-sectional or case-control studies on ANA screening of CTD reporting results for IIF and FEIA. Study quality was assessed using the QUADAS-2 checklist. The reference standard was assessed against established classification criteria. The meta-analysis used hierarchical, bivariate and mixed-effects models to allow test results to vary within and across studies. Eighteen studies of good to fair quality were included in the review. IIF had a higher sensitivity than FEIA [cut-off 1:160, 7 studies, 3251 patients, 0.83 (95% CI 0.75-0.89) versus 0.73 (95% CI 0.64-0.80); cut-off 1:80, 7 studies, 12,311 patients, 0.89 (95% CI 0.84-0.93) versus 0.78 (95% CI 0.71-0.84)] but lower specificity [1:160, 0.81 (95% CI 0.73-0.87) versus 0.94 (95% CI 0.91-0.95); 1:80, 0.72 (95% CI 0.62-0.81) versus 0.94 (95% CI 0.90-0.96)]. A double-positive test had a higher likelihood ratio (LR) for CTD (26.2 (95% CI 23.0-29.9)) than a single positive test (14.4 (95% CI 13.1-15.9) FEIA+, 5.1 (95% CI 4.8-5.4) IIF+). A double-negative test result had more clinical value for ruling out CTD than a single negative test (LR 0.15 (95% CI 0.12-0.18) versus 0.21 (95% CI 0.18-0.25) IIF; 0.33 (95% CI 0.29-0.37) FEIA-). A FEIA+/IIF- discordant result had a higher LR than an IIF+/FEIA- discordant result (LR 2.4 (95% CI 1.7-3.4) versus 1.4 (95% CI 1.2-1.7)). Because of the comparatively higher specificity of FEIA and higher sensitivity of IIF, the combination of FEIA and IIF increases the diagnostic value. Clinicians should be acquainted with the clinical presentation of CTD and aware of the advantages and disadvantages of FEIA and IIF to avoid misinterpretation.status: publishe