@article{fdi:010065529,
  title = {{B}eninese children with cerebral malaria do not develop humoral immunity against the {IT}4-{VAR}19-{DC}8 {P}f{EMP}1 variant linked to {EPCR} and brain endothelial binding [+ erratum, janvier 2016]},
  author = {{N}unes-{S}ilva, {S}. and {D}echavanne, {S}. and {M}oussiliou, {A}. and {P}strag, {N}. and {S}emblat, {J}. {P}. and {G}angnard, {S}. and {T}uikue {N}dam, {N}icaise and {D}eloron, {P}hilippe and {C}h{\^e}ne, {A}. and {G}amain, {B}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {M}alaria is still one of the most prevalent infectious diseases in the world. {S}equestration of infected erythrocytes ({IE}s) is the prime mediator of disease. {C}ytoadhesion of {IE}s is mediated by members of the highly diverse {P}lasmodium falciparum erythrocyte membrane protein 1 ({P}f{EMP}1). {A} restricted sub-set of var genes encoding for {P}f{EMP}1s possessing the domain cassettes {DC}8 and {DC}13 were found to bind to the endothelial protein {C} receptor ({EPCR}). {T}hese var genes were shown to be highly expressed by parasites from patients with severe malaria clinical outcomes compared to those from patients with uncomplicated symptoms. {M}ethods: {I}n order to further study the molecular mechanisms underlying {DC}8/{DC}13 expressing {IE}s adhesion to {EPCR}, a method was developed to produce highly pure recombinant {EPCR}. {T}he {IT}4 parasite strain was selected on either anti-{IT}4-{VAR}19 purified {I}g{G}, {EPCR} or human brain endothelial cell line and their var gene expression profiles as well as their binding phenotypes were compared. {T}he {N}-terminal region of {IT}4-{VAR}19 comprising a full-length {DC}8 cassette as well as the single {EPCR} binding {CIDR} alpha 1.1 domain were also produced, and their immune recognition ({I}g{G}) was assessed using plasma samples from {B}eninese children presenting acute mild malaria, severe malaria or cerebral malaria at the time of their admission to the clinic, and from convalescent-phase plasma collected 30 days after antimalarial treatment. {R}esults: {T}he multi-domain {VAR}19-{NTS}-{DBL} gamma 6 binds to {EPCR} with a greater affinity than the {CIDR} alpha 1.1 domain alone and this study also demonstrates that {VAR}19-{NTS}-{DBL} gamma 6 binding to the {EPCR}-expressing endothelial cell line ({HBEC}5i) is more pronounced than that of the {CIDR} alpha 1.1 domain alone. {IT}4-{VAR}19 represents the preferentially expressed-{P}f{EMP}1 when {FCR}3-{IE}s are selected based on their capability to bind {EPCR}. {N}otably, no significant difference in the levels of antibodies towards {IT}4-{VAR}19 antigens was observed within all clinical groups between plasma samples collected during the acute malaria phase compared to samples collected 30 days after anti-malaria treatment. {C}onclusions: {T}hese data indicate that even being the preferentially selected {IT}4-{EPCR}-binding variant, the {IT}4-{VAR}19-{DC}8 region does not appear to be associated with the acquisition of antibodies during a single severe paediatric malaria episode in {B}enin.},
  keywords = {{E}ndothelial protein {C} receptor ; var genes ; {P}lasmodium falciparum ; erythrocyte membrane protein 1 ; {C}erebral malaria ; {P}lasmodium falciparum ; {I}mmunity ; {BENIN}},
  booktitle = {},
  journal = {{M}alaria {J}ournal},
  volume = {14},
  numero = {},
  pages = {art. 493 [15  + erratum]},
  ISSN = {1475-2875},
  year = {2015},
  DOI = {10.1186/s12936-015-1008-5},
  URL = {https://www.documentation.ird.fr/hor/fdi:010065529},
}