Antinuclear antibody positivity in acute Epstein–Barr virus and cytomegalovirus infections

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are herpesviruses presumed to trigger autoimmunity. This study assessed the association between acute EBV/CMV infection and antinuclear antibody (ANA) seropositivity. We retrospectively reviewed immunocompetent patients with serologically confirmed acute EBV or CMV who were admitted to the Sheba Medical Center (2019-2023). ANA was tested during the differential diagnosis. Patients with autoimmune/neoplastic diseases were excluded. Among 52 patients (56% female, mean age 42 ± 16.8), CMV patients were older than EBV patients (48 ± 15.3 vs. 25 ± 5.5, <i>p</i> < 0.005). ANA was positive in 79% of CMV and 29% of EBV cases (<i>p</i> < 0.005). Positivity was higher in males than in females (87% vs. 48%, <i>p</i> < 0.05). In CMV, 94% of males and 65% of females were ANA-positive (<i>p</i> < 0.05). No autoimmune diseases were diagnosed during a partial (hospital-based) 1-5 year follow-up. In our cohort, ANA seropositivity was observed more frequently in acute CMV infection and was more common among male patients regardless of age. These results warrant further research into the immunological mechanisms underlying ANA production in CMV infections. Given the unclear clinical significance of ANA seropositivity in the context of acute CMV or EBV infection, routine ANA testing in these patients is generally unnecessary and may lead to unwarranted investigations.