@article{fdi:010080902,
  title = {{P}f{EMP}1 {A}-type {ICAM}-1-binding domains are not associated with cerebral {M}alaria in {B}eninese children},
  author = {{J}oste, {V}. and {G}uillochon, {E}. and {F}raering, {J}eremy and {V}ianou, {B}. and {W}atier, {L}. and {G}uemouri, {S}ayeh and {C}ot, {M}ichel and {H}ouze, {S}. and {A}ubouy, {A}gn{\`e}s and {F}aucher, {J}. {F}. and {A}rgy, {N}. and {B}ertin, {G}wladys and {N}euro{CM} {S}tudy {G}roup},
  editor = {},
  language = {{ENG}},
  abstract = {{P}f{EMP}1 is the major antigen involved in {P}lasmodium falciparum-infected erythrocyte sequestration in cerebrovascular endothelium. {W}hile some {P}f{EMP}1 domains have been associated with clinical phenotypes of malaria, formal associations between the expression of a specific domain and the adhesion properties of clinical isolates are limited. {I}n this context, 73 cerebral malaria ({CM}) and 98 uncomplicated malaria ({UM}) {B}eninese children were recruited. {W}e attempted to correlate the cytoadherence phenotype of {P}lasmodium falciparum isolates with the clinical presentation and the expression of specific {P}f{EMP}1 domains. {C}ytoadherence level on {H}bec-5i and {CHO}-{ICAM}-1 cell lines and var genes expression were measured. {W}e also investigated the prevalence of the {ICAM}-1-binding amino acid motif and dual receptor-binding domains, described as a potential determinant of cerebral malaria pathophysiology. {W}e finally evaluated {I}g{G} levels against {P}f{EMP}1 recombinant domains ({CIDR} alpha 1.4, {DBL} beta 3, and {CIDR} alpha 1.4-{DBL} beta 3). {CM} isolates displayed higher cytoadherence levels on both cell lines, and we found a correlation between {CIDR} alpha 1.4 {DBL} beta 1/3 domain expression and {CHO}-{ICAM}-1 cytoadherence level. {E}ndothelial protein {C} receptor ({EPCR})-binding domains were overexpressed in {CM} isolates compared to {UM} whereas no difference was found in {ICAM}-1-binding {DBL} beta 1/3 domain expression. {S}urprisingly, both {CM} and {UM} isolates expressed {ICAM}-1-binding motif and dual receptor-binding domains. {T}here was no difference in {I}g{G} response against {DBL} beta 3 between {CM} and {UM} isolates expressing {ICAM}-1-binding {DB}4 beta/3 domain. {I}t raises questions about the role of this motif in {CM} pathophysiology, and further studies are needed, especially on the role of {DBL} beta 1/3 without the {ICAM}-1-binding motif. {IMPORTANCE} {C}erebral malaria pathophysiology remains unknown despite extensive research. {P}f{EMP}1 proteins have been identified as the main {P}lasmodium antigen involved in cerebrovascular endothelium sequestration, but it is unclear which var gene domain is involved in {P}lasmodium cytoadhesion. {EPCR} binding is a major determinant of cerebral malaria whereas the {ICAM}-1-binding role is still questioned. {O}ur study confirmed the {EPCR}-binding role in {CM} pathophysiology with a major overexpression of {EPCR}-binding domains in {CM} isolates. {I}n contrast, {ICAM}-1-binding involvement appears less obvious with {A}-type {ICAM}-1-binding and dual receptor-binding domain expression in both {CM} and {UM} isolates. {W}e did not find any variations in {ICAM}-1-binding motif sequences in {CM} compared to {UM} isolates. {UM} and {CM} patients infected with isolates expressing the {ICAM}-1-binding motif displayed similar {I}g{G} levels against {DBL} beta 3 recombinant protein. {O}ur study raises interrogations about the role of these domains in {CM} physiopathology and questions their use in vaccine strategies against cerebral malaria.},
  keywords = {cerebral malaria ; var genes ; cytoadherence ; dual receptor binding ; {ICAM}-1-binding motif ; {BENIN}},
  booktitle = {},
  journal = {{M}bio},
  volume = {11},
  numero = {6},
  pages = {e02103--20 [14 ]},
  ISSN = {2150-7511},
  year = {2020},
  DOI = {10.1128/m{B}io.02103-20},
  URL = {https://www.documentation.ird.fr/hor/fdi:010080902},
}