Delayed and reduced adaptive humoral immune responses in children with shigellosis compared with in adults

Abstract

Abstract

We hypothesized that increased susceptibility to Shigella infection, increased severity of disease and high mortality in children compared with adults were consequences of insufficient adaptive immune responses. Antigen-specific immune responses were studied in paediatric patients (n = 38, 2-10 years) with shigellosis and compared with those of adult patients (n = 30, 18-45 years). Peak frequencies of antigen (invasion plasmid coded antigen B, Ipa-B; lipopolysaccharide, LPS)-specific immunoglobulin (IgM)-antibody secreting cells (ASC) were seen within 3-5 days after the onset of diarrhoea in children, while peak IgA- and IgG-ASCs were obtained 8-10 days later in line with adults. Antigen-specific ASC responses in children ranged between 2 and 4% of the total ASC responses, in contrast to 8-15% in adults. The kinetics of LPS-specific IgG subclass titres was different in younger children (2.5-5 years) (IgG1 > IgG2 > IgG4 > IgG3) compared with in older children (6-8 years) (IgG2 > IgG1 >IgG3 > IgG4) and adults. Secretory IgA levels in stool peaked 8-10 days after onset in both adults and children. However, a rapid induction of stool LPS-specific IgA, IgA1 and IgA2 occurred in adult patients within 3-5 days of onset, while in children, this was delayed by 8-10 days. Similarly, higher number of tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma expressing cells in vitro were seen in adult patients in response to antigens (LPS and Ipa-B) in the acute stage in contrast to paediatric patients. Thus, paediatric patients with shigellosis have reduced and delayed adaptive immune responses compared with adult patients