Abstract

Rotavirus nonstructural protein 4 (NSP4) has been suggested as a pathogen of rotavirus-associated seizures. We investigated pre-existing serum antibodies against NSP4 and VP6 (the most highly immunogenic rotavirus protein) in patients with rotavirus gastroenteritis and its correlation with the occurrence of seizures. With an enzyme-linked immunosorbent assay, IgG and IgA titers against NSP4 (genotype [A] and [B]) and VP6 were measured in acute-phase sera of 202 children aged 0.5-6.0 years with rotavirus gastroenteritis. The clinical characteristics and antibody levels were compared between patients with (seizure group) and without seizures (non-seizure group). The non-seizure and seizure groups comprised 173 and 29 patients, respectively. Age, sex, hospital stay, presence of fever, white blood cell counts, C-reactive protein, vaccine status, IgG/IgA titers for VP6, and IgA titers for both NSP4s did not differ between the groups. The seizure group showed a lower level of IgG against NSP4 [A] (184.5 vs. 163.0U/mL; P=0.03) and NSP4 [B] (269.0 vs. 196.0U/mL; P=0.02). Delayed sampling time from the onset of gastroenteritis symptoms (3 vs. 2 days; P=0.02) and lower serum sodium level (133.4 vs. 136.3mEq/L; P<0.01) were observed in the seizure group. Even after adjusting these factors, anti-NSP4 [A] IgG (OR 2.56 per 100U/mL increment; 95% CI, 1.20-5.26, P=0.01) and anti-NSP4 [B] IgG (OR 1.51 per 100U/mL-increment; 95% CI, 1.04-2.22, P=0.03) were independently associated with protection against seizures. Serum anti-NSP4 IgG might protect rotavirus-associated seizures.

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