Antibody responses to the merozoite surface protein-1 complex in cerebral malaria patients in India

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Abstract
Background: Plasmodium falciparuminfection causes cerebral malaria (CM) in a subset of patients with anti-malarial treatment protecting only about 70% to 80% of patients. Why a subset of malaria patients develops CM complications, including neurological sequelae or death, is still not well understood. It is believed that host immune factors may modulate CM outcomes and there is substantial evidence that cellular immune factors, such as cytokines, play an important role in this process. In this study, the potential relationship between the antibody responses to the merozoite surface protein (MSP)-1 complex (which consists of four fragments namely: MSP-183, MSP-130, MSP-138and MSP-142), MSP-636and MSP-722and CM was investigated.Methods: Peripheral blood antibody responses to recombinant antigens of the two major allelic forms of MSP-1 complex, MSP-636and MSP-722were compared between healthy subjects, mild malaria patients (MM) and CM patients residing in a malaria endemic region of central India. Total IgG and IgG subclass antibody responses were determined using ELISA method.Results: The prevalence and levels of IgG and its subclasses in the plasma varied for each antigen. In general, the prevalence of total IgG, IgG1 and IgG3 was higher in the MM patients and lower in CM patients compared to healthy controls. Significantly lower levels of total IgG antibodies to the MSP-1f38, IgG1 levels to MSP-1d83, MSP-119and MSP-636and IgG3 levels to MSP-1f42and MSP-722were observed in CM patients as compared to MM patients.Conclusion: These results suggest that there may be some dysregulation in the generation of antibody responses to some MSP antigens in CM patients and it is worth investigating further whether perturbations of antibody responses in CM patients contribute to pathogenesis.