Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin
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Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin. / Rasti, Niloofar; Namusoke, Fatuma; Chêne, Arnaud; Chen, Qijun; Staalsoe, Trine; Klinkert, Mo-Quen; Mirembe, Florence; Kironde, Fred; Wahlgren, Mats.
In: Proceedings of the National Academy of Science of the United States of America, Vol. 103, No. 37, 2006, p. 13795-800.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin
AU - Rasti, Niloofar
AU - Namusoke, Fatuma
AU - Chêne, Arnaud
AU - Chen, Qijun
AU - Staalsoe, Trine
AU - Klinkert, Mo-Quen
AU - Mirembe, Florence
AU - Kironde, Fred
AU - Wahlgren, Mats
N1 - Keywords: Adolescent; Adult; Animals; Antigens, Protozoan; Cell Adhesion; Chondroitin Sulfates; Erythrocytes; Female; Humans; Hyaluronic Acid; Immunoglobulin G; Immunoglobulin M; Malaria, Falciparum; Placenta; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Parasitic; Protein Interaction Mapping; Protein Structure, Tertiary
PY - 2006
Y1 - 2006
N2 - The harmful effects of pregnancy-associated malaria (PAM) are engendered by the heavy sequestration of Plasmodium falciparum-parasitized RBCs in the placenta. It is well documented that this process is mediated by interactions of parasite-encoded variant surface antigens and placental receptors. A P. falciparum erythrocyte membrane protein 1 variant, VAR2CSA, and the placental receptor chondroitin sulfate A (CSA) are currently the focus of PAM research. A role for immunoglobulins (IgG and IgM) from normal human serum and hyaluronic acid as additional receptors in placental sequestration have also been suggested. We show here (i) that CSA and nonimmune IgG/IgM binding are linked phenotypes of in vitro-adapted parasites, (ii) that a VAR2CSA variant shown to bind CSA also harbors IgG- and IgM-binding domains (DBL2-X, DBL5-epsilon, and DBL6-epsilon), and (iii) that IgG and IgM binding and adhesion to multiple receptors (IgG/IgM/HA/CSA) rather than the exclusive binding to CSA is a characteristic of fresh Ugandan placental isolates. These findings are of importance for the understanding of the pathogenesis of placental malaria and have implications for the ongoing efforts to develop a global PAM vaccine.
AB - The harmful effects of pregnancy-associated malaria (PAM) are engendered by the heavy sequestration of Plasmodium falciparum-parasitized RBCs in the placenta. It is well documented that this process is mediated by interactions of parasite-encoded variant surface antigens and placental receptors. A P. falciparum erythrocyte membrane protein 1 variant, VAR2CSA, and the placental receptor chondroitin sulfate A (CSA) are currently the focus of PAM research. A role for immunoglobulins (IgG and IgM) from normal human serum and hyaluronic acid as additional receptors in placental sequestration have also been suggested. We show here (i) that CSA and nonimmune IgG/IgM binding are linked phenotypes of in vitro-adapted parasites, (ii) that a VAR2CSA variant shown to bind CSA also harbors IgG- and IgM-binding domains (DBL2-X, DBL5-epsilon, and DBL6-epsilon), and (iii) that IgG and IgM binding and adhesion to multiple receptors (IgG/IgM/HA/CSA) rather than the exclusive binding to CSA is a characteristic of fresh Ugandan placental isolates. These findings are of importance for the understanding of the pathogenesis of placental malaria and have implications for the ongoing efforts to develop a global PAM vaccine.
U2 - 10.1073/pnas.0601519103
DO - 10.1073/pnas.0601519103
M3 - Journal article
C2 - 16945914
VL - 103
SP - 13795
EP - 13800
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 37
ER -
ID: 17274452