Pattern of humoral immune response to Plasmodium falciparum blood stages in individuals presenting different clinical expressions of malaria

Abstract\ud \ud \ud \ud Background\ud \ud The development of protective immunity against malaria is slow and to be maintained, it requires exposure to multiple antigenic variants of malaria parasites and age-associated maturation of the immune system. Evidence that the protective immunity is associated with different classes and subclasses of antibodies reveals the importance of considering the quality of the response. In this study, we have evaluated the humoral immune response against Plasmodium falciparum blood stages of individuals naturally exposed to malaria who live in endemic areas of Brazil in order to assess the prevalence of different specific isotypes and their association with different malaria clinical expressions.\ud \ud \ud \ud Methods\ud \ud Different isotypes against P. falciparum blood stages, IgG, IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA, were determined by ELISA. The results were based on the analysis of different clinical expressions of malaria (complicated, uncomplicated and asymptomatic) and factors related to prior malaria exposure such as age and the number of previous clinical malaria attacks. The occurrence of the H131 polymorphism of the FcγIIA receptor was also investigated in part of the studied population.\ud \ud \ud \ud Results\ud \ud The highest levels of IgG, IgG1, IgG2 and IgG3 antibodies were observed in individuals with asymptomatic and uncomplicated malaria, while highest levels of IgG4, IgE and IgM antibodies were predominant among individuals with complicated malaria. Individuals reporting more than five previous clinical malaria attacks presented a predominance of IgG1, IgG2 and IgG3 antibodies, while IgM, IgA and IgE antibodies predominated among individuals reporting five or less previous clinical malaria attacks. Among individuals with uncomplicated and asymptomatic malaria, there was a predominance of high-avidity IgG, IgG1, IgG2 antibodies and low-avidity IgG3 antibodies. The H131 polymorphism was found in 44.4% of the individuals, and the highest IgG2 levels were observed among asymptomatic individuals with this allele, suggesting the protective role of IgG2 in this population.\ud \ud \ud \ud Conclusion\ud \ud Together, the results suggest a differential regulation in the anti-P. falciparum antibody pattern in different clinical expressions of malaria and showed that even in unstable transmission areas, protective immunity against malaria can be observed, when the appropriated antibodies are produced.We would like to especially thank Dr. Cristóvão Luis Pitangueira Mangueira, Flávia Cristina Kinskowski and Milca Geane de Lamos Valim at the Central Laboratory of the Clinical Hospital for participating in the determination of the total IgE and IgA levels. This work was supported by FAPESP (process number 2001/04073-5) and Laboratório de Investigações Médicas do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (LIM-48/HCFMUSP)We would like to especially thank Dr. Cristóvão Luis Pitangueira Mangueira, Flávia Cristina Kinskowski and Milca Geane de Lamos Valim at the Central Laboratory of the Clinical Hospital for participating in the determination of the total IgE and IgA levels. This work was supported by FAPESP (process number 2001/040735) and Laboratório de Investigações Médicas do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (LIM48/HCFMUSP