The Usefulness of Antinuclear Antibody Multiplex Immunoassay for Screening of Rheumatological Diseases: A Real-World Population-Based Study.

OBJECTIVE

To evaluate the diagnostic performance of BioPlex 2200 multiplex immunoassay (BI) for detecting antinuclear antibodies (ANA), compared with the gold standard, the indirect immunofluorescence assay (IIF), as a screening methodology for autoimmune diseases within a general population.

METHODS

Cross-sectional, database-based analysis of the Clalit Health Services nationwide registry. Data were extracted from the Clalit Health Services database between 2014 and 2023. We included adult outpatients without a known rheumatic disease who underwent both IIF and BI testing simultaneously, ordered for nonspecific signs and symptoms primarily by primary-care physicians.

RESULTS

Among the 391,366 individuals tested, 67% were female, and the median age at testing was 49 years. Annual ANA testing volume increased from 23,802 in 2014 to 76,898 in 2023 (3.2-fold). Of the total, 33,234 (8.4%) tests were false negatives (BI-negative while IIF-positive), 42,021 (10.7%) were false positives (BI-positive while IIF-negative), 302,439 (77.2%) were true negatives, and 13,672 (3.5%) were true positives. BI demonstrated a sensitivity of 29.1% (95% CI: 28.7-29.6) and a specificity of 87.8% (95% CI: 87.7-87.9). The positive predictive value was 24.5% and the negative predictive value 90.1%.

CONCLUSION

Our findings do not support the use of the BI multiplex immunoassay as a primary ANA screening tool in the primary-care setting. On the basis of these findings, the Clalit Health Services laboratory network discontinued simultaneous IIF and BI testing.

KEY FINDINGS: The BI showed low sensitivity despite relatively high specificity, resulting in a substantial proportion of false-negative results compared with IIF. These findings indicate that it is not suitable as a primary screening tool for ANA in the primary-care setting.