ENA Seropositivity in ANA-Negative Patients: A Meta-Analysis of 28 Studies

28 studies comprising 33 patient groups and 28,552 ANA-IIF–negative samples were analyzed. The pooled proportion of extractable nuclear antigen (ENA) seropositivity among antinuclear antibody (ANA)-negative individuals was 14.1%, with significant variation by clinical indication. This systematic review and meta-analysis by Tarak Dhaouadi was published on figshare in 2026.

Use Cases

• Estimating the frequency of ENA seropositivity in ANA-negative patients based on the pooled proportion of 14.1%.
• Investigating clinical determinants of ENA+/IIF− status based on subgroup analysis by clinical indication (e.g., suspected vs. confirmed CTD).
• Evaluating methodological factors influencing test results based on identified determinants like IIF cut-off dilution and specific antibody types.
• Informing clinical testing strategies for connective tissue disease based on the finding that a negative ANA-IIF does not reliably exclude CTD.

Strengths

• Analysis is based on a substantial sample size of 28,552 ANA-IIF–negative samples.
• Includes 28 studies with 33 distinct patient groups, providing a broad evidence base.
• Results are stratified by clinical context, showing proportions from 1.4% to 44.1%.
• The work is a formal systematic review and meta-analysis registered with PROSPERO (CRD420250654499).

Limitations

• The primary data file is a 799.4 KB DOCX document; the underlying raw dataset (columns, rows) is unavailable for direct analysis.
• Description metadata is limited; actual data quality requires manual inspection after download.
• Substantial heterogeneity was reported (I² = 99%), which may complicate interpretation of the pooled estimate.

Provenance

Source

figshare, author Tarak Dhaouadi.

Collection Method

Systematic search of PubMed, EMBASE, Web of Science, and Scopus for studies published up to January 31, 2025, followed by meta-analysis.

Time Range

Studies published up to January 31, 2025.

Freshness

Last updated 2026-04-28 05:24:12; freshness should be verified.