Rotavirus-specific subclass antibody and cytokine responses in Bangladeshi children with rotavirus diarrhoea

Rotavirus-specific subclass antibody responses and cytokines, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-8 (IL-8), and IL-10, were measured in children 7-24 months of age with rotavirus diarrhoea (n = 29); the responses were compared with children with watery diarrhoea from whom no enteric pathogens were isolated (controls; n = 11). All children had diarrhoea for <5 days and were enrolled from the Dhaka Hospital of the Centre for Health and Population Research. Samples of blood and stools were collected on the day of enrollment and 18-21 days after the onset of diarrhoea. Children showing a ≥4-fold rise in antibody titre between the acute and convalescent stages were considered to have a response. The numbers of children with rotavirus-specific IgA and IgA1 responses in stool were similar in the two groups of children. In the plasma, more children with rotavirus diarrhoea had rotavirus-specific IgA, IgA1, IgG, IgG1, and IgG3 responses than did control children (P = 0.049, 0.007, 0.001, 0.002, and 0.012, respectively). IgA2 was not detectable. Among cytokines measured in supernatants from peripheral blood mononuclear cells (PBMCs) cultured for 6 and 24 hr, IFN-γ was the only cytokine that was higher in children with rotavirus diarrhoea compared with controls (P = 0.013). Severity of illness did not correlate with nutritional status or antibody titres, but severity did correlate with TNF-α during the acute stage of illness. IFN-γ correlated positively with IgG1 titres. These findings suggest a role for IFN-γ in the pathogenesis of rotavirus infection, but this needs confirmation by other studies. The immune responses described are relevant to future vaccine trials, as immune responses in vaccinees should mimic those in natural infection.