High immunoglobulin G2 (IgG2) and low IgG4 levels are associated with human resistance to XXXX @entity311 .

@entity281 @entity311 @entity137 @entity3964
There is accumulating evidence for a role of immunoglobulin G (IgG) in protection against @entity281 . Only IgG1 and IgG3 are considered cytophilic and protective against P. falciparum, whereas IgG2 and IgG4 were thought to be neither and even to block protective mechanisms. However, no clear pattern of association between isotypes and protection has so far emerged. We analyzed the isotypic distribution of the IgG response to conserved epitopes and @entity3964 blood-stage extract in 283 @entity311 -exposed individuals whose occurrence of @entity281 and @entity311 attack had been monitored for about 1 year. Logistic regression analyses showed that, at the end of the season of transmission, high levels of IgG2 to RESA and to MSP2 epitopes were associated with low risk of @entity281 . Indeed, IgG2 is able to bind FcgammaRIIA in individuals possessing the H131 allele, and we showed that 70% of the study subjects had this allele. Also, high specific IgG4 levels were associated with an enhanced risk of @entity281 and with a high risk of @entity311 attack. Moreover, specific IgG2 and IgG3 levels, as well as the IgG2/IgG4 and IgG3/IgG4 ratios, increased with the age of subjects, in parallel with the protection against @entity281 . IgG4 likely competes with cytophilic antibodies for antigen recognition and may therefore @entity137 mediated by antibody-activated effector cells. In conclusion, these results favor a protective role of IgG3 and IgG2, which may activate effector cells through FcgammaRIIA, and provide evidence for a blocking role of IgG4 in @entity281 .
