Total and Protein E-specific antibody secreting cells response in pediatric dengue is age-related and modulated by sub-sequent infections
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1
Universidad Surcolombiana - Hospital Universitario de Neiva, Facultad de Salud, Programa de Medicina, Colombia
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2
Pontificia Universidad Javeriana, Instituto de Genética Humana, Colombia
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3
Stanford University Medical School, Department of Microbiology & Immunology, United States
Antibodies play a critical role in both the protection from and pathogenesis of dengue infection. Recently, the antibody-secreting cells (ASC) induced by dengue infection have begun to be characterized, particularly in adults and children with secondary infection. For dengue vaccine studies, the dissection of factors that modulate the antibody as well as the ASC response in young children are highly necessaries. We propose that age and the base-line immune status are critical determinants of the ASC response generated in dengue-infected children. Here, total non antigen-specific (by flow cytometry and two color ELISPOT) and protein E-specific (prot-E) ASC response (by two color ELISPOT using recombinant envelope protein from 4 dengue serotypes) were analyzed in 116 pediatric patients (including 35 infants, 6 to 12 months age and 81 children 1-14 years old) with primary (1º) or secondary (2º) infection and clinically ranging from mild to severe dengue. Forty healthy children were also included as controls. For dengue diagnosis and clinical follow-up, the revised WHO 2009 guideline was used. In a large fraction of patients, several samples during the acute (day-to-day to establish ASC dynamic) and convalescent phases were analyzed. Plasma titers of dengue-specific IgM and IgG antibodies were evaluated by ELISA to determine their relationship to the frequency of ASC. In children with 2º infections, the ASC response was massive and dominated by IgG-ASC, as previously noted. However, the ASC response in infants was less intense and delayed compared to older children with 1º or 2º infection. In 1º infection (dengue-specific IgG undetectable in acute phase), the IgM/IgG ratio of total and prot E-specific ASC, was higher in infants than older children (P<0.02, Mann-Whitney test), suggesting that in infants the IgG isotype switch occurs slowly. In agreement, plasma titers of dengue-IgM were significantly higher in infants than children and an interesting negative correlation between the age and the frequency of prot E-specific IgM ASC in 1º infection was found (rho=-0.6, P=0.03, Spearman test). Infants with detectable dengue-specific IgG in acute phase developed an early high frequency of total and prot E-specific IgG ASC, comparable to children with 2º infection. Thus, two simple factors modulated the ASC response in pediatric dengue: the age and previous infection status. In 1º and 2º infections, ASC response was highly cross-reactive between 4 serotypes. Finally, severe pediatric dengue was associated with significant higher frequencies of Prot-E specific IgM and IgG-ASC in infants and children, respectively (P=0.04, P=0.02 no severe Vs severe dengue, respectively, Mann-Whitney test). In summary, the ASC response in pediatric dengue is strongly modulated by the age and the previous infection history and their magnitude is a relevant factor in the clinical outcome. These results are helpful to define aspects unknown currently, as the optimal age for massive dengue vaccination.
Acknowledgements
This work was funded by COLCIENCIAS, grant 112451929053 (to CFN).
Keywords:
Dengue,
B cells,
antibody secreting cells,
plasmablasts,
Elispot
Conference:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.
Presentation Type:
Oral Presentation
Topic:
Infectious and parasitic diseases
Citation:
Toro
J,
Salgado
DM,
Rodríguez
J,
Vega
R,
Rodríguez
L,
Angel
J,
Franco
MA,
Greenberg
HB and
Narváez
CF
(2015). Total and Protein E-specific antibody secreting cells response in pediatric dengue is age-related and modulated by sub-sequent infections.
Front. Immunol.
Conference Abstract:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología.
doi: 10.3389/conf.fimmu.2015.05.00339
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Received:
12 May 2015;
Published Online:
15 Sep 2015.
*
Correspondence:
MD, PhD. Carlos F Narváez, Universidad Surcolombiana - Hospital Universitario de Neiva, Facultad de Salud, Programa de Medicina, Neiva, Colombia, cfnarvaez@usco.edu.co