title: Delayed and reduced adaptive humoral immune responses in children with shigellosis compared with in adults.
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.
authors.affiliation: International Centre for Diarrhoeal Diseases Research, ICDDR, B, Dhaka, Bangladesh. rubhana@icddrb.org
authors.forename: R
authors.initials: R
authors.lastname: Raqib
authors.forename: F
authors.initials: F
authors.lastname: Qadri
authors.forename: P
authors.initials: P
authors.lastname: SarkEr
authors.forename: S M S
authors.initials: SM
authors.lastname: Mia
authors.forename: P J
authors.initials: PJ
authors.lastname: Sansonnetti
authors.forename: M J
authors.initials: MJ
authors.lastname: Albert
authors.forename: J
authors.initials: J
authors.lastname: Andersson
mesh_terms: D000222:Adaptation, Physiological; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000907:Antibodies, Bacterial / Q000097:blood*; D000921:Antibody-Producing Cells / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D004405:Dysentery, Bacillary / Q000276:immunology*; D005243:Feces / Q000382:microbiology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D008070:Lipopolysaccharides / Q000276:immunology; D008875:Middle Aged; D013997:Time Factors
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides