Delayed and reduced adaptive humoral immune responses in children with shigellosis compared with in adults |
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Authors: | Raqib R Qadri F SarkEr P Mia S M S Sansonnetti P J Albert M J Andersson J |
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Affiliation: | International Centre for Diarrhoeal Diseases Research, ICDDR, B, Dhaka, Bangladesh. rubhana@icddrb.org |
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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. |
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