title: Total and Envelope Protein-Specific Antibody-Secreting Cell Response in Pediatric Dengue Is Highly Modulated by Age and Subsequent Infections.
abstract: The response of antibody-secreting cells (ASC) induced by dengue has only recently started to be characterized. We propose that young age and previous infections could be simple factors that affect this response. Here, we evaluated the primary and secondary responses of circulating ASC in infants (6-12 months old) and children (1-14 years old) infected with dengue showing different degrees of clinical severity. The ASC response was delayed and of lower magnitude in infants, compared with older children. In primary infection (PI), the total and envelope (E) protein-specific IgM ASC were dominant in infants but not in children, and a negative correlation was found between age and the number of IgM ASC (rho = -0.59, P = 0.03). However, infants with plasma dengue-specific IgG detectable in the acute phase developed an intense ASC response largely dominated by IgG and comparable to that of children with secondary infection (SI). IgM and IgG produced by ASC circulating in PI or SI were highly cross-reactive among the four serotypes. Dengue infection caused the disturbance of B cell subsets, particularly a decrease in the relative frequency of naïve B cells. Higher frequencies of total and E protein-specific IgM ASC in the infants and IgG in the children were associated with clinically severe forms of infection. Therefore, the ASC response induced by dengue is highly influenced by the age at which infection occurs and previous immune status, and its magnitude is a relevant element in the clinical outcome. These results are important in the search for correlates of protection and for determining the ideal age for vaccinating against dengue.
authors: Programa de Medicina, Facultad de Salud, Universidad Surcolombiana, Neiva, Colombia.|Departamento de Pediatría, Hospital Universitario de Neiva, Neiva, Colombia.
authors: Jessica F
authors: JF
authors: Toro
authors: Programa de Medicina, Facultad de Salud, Universidad Surcolombiana, Neiva, Colombia.|Departamento de Pediatría, Hospital Universitario de Neiva, Neiva, Colombia.
authors: Doris M
authors: DM
authors: Salgado
authors: Programa de Medicina, Facultad de Salud, Universidad Surcolombiana, Neiva, Colombia.|Departamento de Pediatría, Hospital Universitario de Neiva, Neiva, Colombia.
authors: Rocío
authors: R
authors: Vega
authors: Programa de Medicina, Facultad de Salud, Universidad Surcolombiana, Neiva, Colombia.|Departamento de Pediatría, Hospital Universitario de Neiva, Neiva, Colombia.
authors: Jairo A
authors: JA
authors: Rodríguez
authors: Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors: Luz-Stella
authors: LS
authors: Rodríguez
authors: Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors: Juana
authors: J
authors: Angel
authors: Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors: Manuel A
authors: MA
authors: Franco
authors: Departments of Medicine and Microbiology & Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
authors: Harry B
authors: HB
authors: Greenberg
authors: Programa de Medicina, Facultad de Salud, Universidad Surcolombiana, Neiva, Colombia.
authors: Carlos F
authors: CF
authors: Narváez
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000921:Antibody-Producing Cells / Q000276:immunology* / Q000821:virology; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions / Q000276:immunology; D003715:Dengue / Q000097:blood / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007223:Infant; D008297:Male; D065288:Serogroup; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014759:Viral Envelope Proteins