Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory cytokines are associated with severe malaria in Mozambican children: a case–control study

Rovira-Vallbona Eduard, Moncunill Gemma, Bassat Quique, Aguilar Ruth, Machevo Sonia, Puyol Laura, Quintó Llorenç, Menéndez Clara, Chitnis, Alonso, Dobaño Carlota, Mayor Alfredo

Description

The factors involved in the progression from Plasmodium falciparum infection to severe malaria (SM) are still incompletely understood. Altered antibody and cellular immunity against P. falciparum might contribute to increase the risk of developing SM. Methods To identify immune responses associated with SM, a sex- and age-matched case–control study was carried out in 134 Mozambican children with SM (cerebral malaria, severe anaemia, acidosis and/or respiratory distress, prostration, hypoglycaemia, multiple seizures) or uncomplicated malaria (UM). IgG and IgM against P. falciparum lysate, merozoite antigens (MSP-1 19 , AMA-1 and EBA-175), a Duffy binding like (DBL)-α rosetting domain and antigens on the surface of infected erythrocytes were measured by ELISA or flow cytometry. Plasma concentrations of IL-12p70, IL-2, IFN-γ, IL-4, IL-5, IL-10, IL-8, IL-6, IL-1β, TNF, TNF-β and TGF-β1 were measured using fluorescent bead immunoassays. Data was analysed using McNemar’s and Signtest. Results Compared to UM, matched children with SM had reduced levels of IgG against DBLα ( P < 0.001), IgM against MSP-1 19 ( P = 0.050) and AMA-1 ( P = 0.047), TGF-β1 ( P <0.001) and IL-12 ( P = 0.039). In addition, levels of IgG against P. falciparum lysate and IL-6 concentrations were increased ( P = 0.004 and P = 0.047, respectively). Anti-DBLα IgG was the only antibody response associated to reduced parasite densities in a multivariate regression model ( P = 0.026) . Conclusions The lower levels of antibodies found in children with SM compared to children with UM were not attributable to lower exposure to P. falciparum in the SM group. IgM against P. falciparum and specific IgG against a rosetting Pf EMP1 domain may play a role in the control of SM, whereas an imbalanced pro-inflammatory cytokine response may exacerbate the severity of infection. A high overlap in symptoms together with a limited sample size of different SM clinical groups reduced the power to identify immunological correlates for particular forms of SM.

Sujets

• Plasmodium falciparum
• Children
• Antibodies
• Cytokine

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 11
• Langue: English

Extrait

RoviraVallbonaet al. Malaria Journal2012,11:181 http://www.malariajournal.com/content/11/1/181

R E S E A R C H

Open Access

Low antibodies againstPlasmodium falciparum and imbalanced proinflammatory cytokines are associated with severe malaria in Mozambican children: a case–control study 1*†1†2 11,2 1,2 Eduard RoviraVallbona , Gemma Moncunill , Quique Bassat , Ruth Aguilar , Sonia Machevo , Laura Puyol , 1 1,2 3 1,2 1,2†1,2† Llorenç Quintó , Clara Menéndez , Chetan E Chitnis , Pedro L Alonso , Carlota Dobaño and Alfredo Mayor

Abstract Background:The factors involved in the progression fromPlasmodium falciparuminfection to severe malaria (SM) are still incompletely understood. Altered antibody and cellular immunity againstP. falciparummight contribute to increase the risk of developing SM. Methods:To identify immune responses associated with SM, a sex and agematched case–control study was carried out in 134 Mozambican children with SM (cerebral malaria, severe anaemia, acidosis and/or respiratory distress, prostration, hypoglycaemia, multiple seizures) or uncomplicated malaria (UM). IgG and IgM againstP. falciparumlysate, merozoite antigens (MSP1 19 , AMA1 and EBA175), a Duffy binding like (DBL)αrosetting domain and antigens on the surface of infected erythrocytes were measured by ELISA or flow cytometry. Plasma concentrations of IL12p70, IL2, IFNγ, IL4, IL5, IL10, IL8, IL6, IL1β, TNF, TNFβand TGFβ1 were measured using fluorescent bead immunoassays. Data was analysed using McNemar’s and Signtest. Results:Compared to UM, matched children with SM had reduced levels of IgG against DBLα(P<0.001), IgM against MSP1 19 (P= 0.050) and AMA1 (PTGF= 0.047), β1 (P<0.001) and IL12 (PIn addition, levels of IgG= 0.039). againstP. falciparumlysate and IL6 concentrations were increased (Pand= 0.004 Prespectively). AntiDBL= 0.047, α IgG was the only antibody response associated to reduced parasite densities in a multivariate regression model (P= 0.026). Conclusions:The lower levels of antibodies found in children with SM compared to children with UM were not attributable to lower exposure toP. falciparumin the SM group. IgM againstP. falciparumand specific IgG against a rosettingPfEMP1 domain may play a role in the control of SM, whereas an imbalanced proinflammatory cytokine response may exacerbate the severity of infection. A high overlap in symptoms together with a limited sample size of different SM clinical groups reduced the power to identify immunological correlates for particular forms of SM. Keywords:Plasmodium falciparum, Children, Severe malaria, Antibodies, Cytokines

* Correspondence:[e-mail] † Equal contributors 1 Barcelona Centre for International Health Research, (CRESIB, Hospital Clínic Universitat de Barcelona), Barcelona, Spain Full list of author information is available at the end of the article

© 2012 RoviraVallbona et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.