Parvovirus B19 serological states and antinuclear antibody positivity: A comparative clinical virology study including EBV and CMV DNAemia.

BACKGROUND

Acute viral infections can mimic systemic autoimmune rheumatic disease (SARD), and concurrent antinuclear antibody (ANA) screening may complicate diagnostic interpretation. Whether Parvovirus B19 (B19V) serological and molecular states differ in their association with ANA positivity remains uncharacterized.

METHODS

This retrospective cross-sectional study stratified 205 immunocompetent patients into seven synchronized groups: acute B19V infection, past B19V infection, B19V-DNA+/IgM- profile, atypical B19V, B19V-naive status, Epstein-Barr virus (EBV) DNAemia, and cytomegalovirus (CMV) DNAemia. Group-defining molecular testing, applicable viral serology, and ANA IIF were performed on paired plasma and serum specimens obtained from the same venipuncture or within 24 hours. ANA positivity, titers, and ICAP-standardized indirect immunofluorescence patterns were assessed. Multivariable logistic regression evaluated factors independently associated with ANA positivity, while exploratory ROC analyses assessed discriminatory performance.

RESULTS

ANA positivity differed significantly across groups (p = 0.001), peaking in EBV DNAemia (53.3%) and acute B19V infection (33.3%), compared with 6.7% in B19V-naive individuals. In age- and sex-adjusted multivariable analysis, EBV DNAemia (adjusted OR 15.05, 95% CI 2.92-77.62; p = 0.001) and acute B19V infection (adjusted OR 6.24, 95% CI 1.22-32.00; p = 0.028) were independently associated with ANA positivity. ANA reactivity was predominantly low-titer and exclusively nuclear. Exploratory ROC analyses showed modest discriminatory performance.

CONCLUSIONS

EBV DNAemia and acute B19V infection are independently associated with increased ANA positivity in this cohort. Low-titer, exclusively nuclear reactivity is compatible with low-intensity, infection-associated autoreactivity rather than established SARD; however, whether this reactivity is transient requires longitudinal confirmation. These findings highlight the importance of virological context in ANA interpretation.