TY - JOUR

T1 - 3D7-derived Plasmodium falciparum erythrocyte membrane protein 1 is a frequent target of naturally acquired antibodies recognizing protein domains in a particular pattern independent of malaria transmission intensity

AU - Joergensen, Louise

AU - Vestergaard, Lasse S

AU - Turner, Louise

AU - Magistrado, Pamela

AU - Lusingu, John P

AU - Lemnge, Martha

AU - Theander, Thor G

AU - Jensen, Anja T R

N1 - Keywords: Adolescent; Adult; Animals; Antibodies, Protozoan; Antibody Specificity; Antigenic Variation; Child; Child, Preschool; Female; Host-Parasite Interactions; Humans; Immunoglobulin G; Malaria, Falciparum; Male; Plasmodium falciparum; Protein Structure, Tertiary; Protozoan Proteins; Tanzania

PY - 2007

Y1 - 2007

N2 - Protection against Plasmodium falciparum malaria is largely mediated by IgG against surface Ags such as the erythrocyte membrane protein 1 family (PfEMP1) responsible for antigenic variation and sequestration of infected erythrocytes. PfEMP1 molecules can be divided into groups A, B/A, B, C, and B/C. We have previously suggested that expression of groups A and B/A PfEMP1 is associated with severe disease and that Abs to these molecules are acquired earlier in life than Abs to PfEMP1 belonging to groups B, B/C, and C PfEMP1. In this study, we compared the acquisition of IgG to 20 rPfEMP1 domains derived from 3D7 in individuals living under markedly different malaria transmission intensity and were unable to find differences in the Ab acquisition rate to PfEMP1 of different groupings (A, B, or C) or domain type (alpha, beta, gamma, delta, epsilon, or x). Abs were acquired early in life in individuals living in the high transmission village and by the age of 2-4 years most individuals had Abs against most constructs. This level of reactivity was found at the age of 10-20 years in the medium transmission village and was never reached by individuals living under low transmission. Nevertheless, the sequence by which individuals acquired Abs to particular constructs was largely the same in the three villages. This indicates that the pattern of PfEMP1 expression by parasites transmitted at the different sites was similar, suggesting that PfEMP1 expression is nonrandom and shaped by host-parasite relationship factors operating at all transmission intensities.

AB - Protection against Plasmodium falciparum malaria is largely mediated by IgG against surface Ags such as the erythrocyte membrane protein 1 family (PfEMP1) responsible for antigenic variation and sequestration of infected erythrocytes. PfEMP1 molecules can be divided into groups A, B/A, B, C, and B/C. We have previously suggested that expression of groups A and B/A PfEMP1 is associated with severe disease and that Abs to these molecules are acquired earlier in life than Abs to PfEMP1 belonging to groups B, B/C, and C PfEMP1. In this study, we compared the acquisition of IgG to 20 rPfEMP1 domains derived from 3D7 in individuals living under markedly different malaria transmission intensity and were unable to find differences in the Ab acquisition rate to PfEMP1 of different groupings (A, B, or C) or domain type (alpha, beta, gamma, delta, epsilon, or x). Abs were acquired early in life in individuals living in the high transmission village and by the age of 2-4 years most individuals had Abs against most constructs. This level of reactivity was found at the age of 10-20 years in the medium transmission village and was never reached by individuals living under low transmission. Nevertheless, the sequence by which individuals acquired Abs to particular constructs was largely the same in the three villages. This indicates that the pattern of PfEMP1 expression by parasites transmitted at the different sites was similar, suggesting that PfEMP1 expression is nonrandom and shaped by host-parasite relationship factors operating at all transmission intensities.

M3 - Journal article

C2 - 17182581

VL - 178

SP - 428

EP - 435

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -