학술논문

Analysis of antibody responses to selected Plasmodium falciparum merozoite surface antigens in mild and cerebral malaria and associations with clinical outcomes.
Document Type
Article
Source
Clinical & Experimental Immunology. Apr2019, Vol. 196 Issue 1, p86-96. 11p. 2 Charts, 5 Graphs.
Subject
*CEREBRAL malaria
*CELL surface antigens
*ANTIBODY formation
Language
ISSN
0009-9104
Abstract
Summary: Merozoite surface proteins (MSPs) are critical for parasite invasion; they represent attractive targets for antibody‐based protection against clinical malaria. To identify protection‐associated target MSPs, the present study analysed antibody responses to whole merozoite extract (ME) and to defined MSP recombinant antigens in hospitalized patients from a low endemic urban area as a function of disease severity (mild versus cerebral malaria). Sera from 110 patients with confirmed severe cerebral malaria (CM) and 91 patients with mild malaria (MM) were analysed (mean age = 29 years) for total and subclass immunoglobulin (Ig)G to ME and total IgG to MSP1p19, MSP2, MSP3, MSP4 and MSP5 by enzyme‐linked immunosorbent assay (ELISA). Functional antibody responses were evaluated using the antibody‐dependent respiratory burst (ADRB) assay in a subset of sera. There was a trend towards higher IgG1 and IgG4 levels to ME in CM compared to MM; only ME IgM responses differed significantly between fatal and surviving CM patients. Increased prevalence of IgG to individual MSPs was found in the CM compared to the MM group, including significantly higher levels of IgG to MSP4 and MSP5 in the former. Sera from fatal (24·5%) versus surviving cases showed significantly lower IgG to MSP1p19 and MSP3 (P < 0·05). ADRB assay readouts correlated with high levels of anti‐MSP IgG, and trended higher in sera from patients with surviving compared to fatal CM outcome (P = 0·07). These results document strong differential antibody responses to MSP antigens as targets of protective immunity against CM and in particular MSP1p19 and MSP3 as prognostic indicators. Ab responses to whole merozoite and to defined MSP recombinant antigens was in hospitalized patients from a low endemic urban area as a function of disease severity (mild vs cerebral malaria and fatal outcome). A trend toward higher Ab levels was found in cerebral malaria compared to mild malaria but lower levels to MSP1p19 and MSP3 in fatal cases compared to surviving. These results document strong differential antibody responses to MSP antigens as targets of protective immunity against cerebral malaria. [ABSTRACT FROM AUTHOR]