@article{fdi:010085926,
  title = {{S}plenic clearance of rigid erythrocytes as an inherited mechanism for splenomegaly and natural resistance to malaria},
  author = {{H}enry, {B}. and {V}olle, {G}. and {A}kpovi, {H}. and {G}ineau, {L}. and {R}oussel, {C}. and {N}dour, {P}. {A}. and {T}ossou, {F}. and {S}uarez, {F}. and {P}alstra, {F}. and {F}ricot, {A}. and {C}hambrion, {C}. and {S}olinc, {J}. and {N}guyen, {J}. and {G}are, {M}. and {A}ussenac, {F}. and {C}ottart, {C}. {H}. and {K}eyser, {C}. and {A}damou, {R}. and {T}ichit, {M}. and {H}ardy, {D}. and {F}ievet, {N}adine and {C}lain, {J}. and {G}arcia, {A}ndr{\'e} and {C}ourtin, {D}avid and {H}ermine, {O}. and {S}abbagh, {A}. and {B}uffet, {P}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground {I}n malaria-endemic areas, subjects from specific groups like {F}ulani have a peculiar protection against malaria, with high levels of {I}g{M} but also frequent anaemia and splenomegaly. {T}he mechanisms underlying this phenotype remain elusive. {M}ethods {I}n a cohort study set up in {B}enin, {W}est {A}frica, after a careful evaluation of malaria-related phenotypes, we measured the deformability of circulating erythrocytes in genetically distinct groups (including {F}ulani) living in sympatry, using ektacytometry and microsphiltration, a mimic of how the spleen clears rigid erythrocytes. {H}eritability of erythrocytes deformability was calculated, followed by a genome-wide association study ({GWAS}) of the same phenotype. {F}indings {C}ompared to non-{F}ulani, {F}ulani displayed a higher deformability of circulating erythrocytes, pointing to an enhanced clearance of rigid erythrocytes by the spleen. {T}his phenotype was observed in individuals displaying markers of {P}lasmodium falciparum infection. {T}he heritability of this new trait was high, with a strong multigenic component. {F}ive of the top io genes selected by a population structure-adjusted {GWAS}, expressed in the spleen, are potentially involved in splenic clearance of erythrocytes ({CHERP}, {MB}, {PALLD}, {SPARC}, {PDE}10{A}), through control of vascular tone, collagen synthesis and macrophage activity. {I}nterpretation {I}n specific ethnic groups, genetically-controlled processes likely enhance the innate retention of infected and uninfected erythrocytes in the spleen, explaining splenomegaly, anaemia, cryptic intrasplenic parasite loads, hyper-{I}g{M}, and partial protection against malaria. {B}eyond malaria-related phenotypes, inherited splenic hyper-filtration of erythrocytes may impact the pathogenesis of other hematologic diseases.},
  keywords = {{M}alaria ; {F}alciparum ; {S}pleen ; {E}rythrocytes ; {E}thnic groups ; {H}eritability ; {S}plenomegaly ; {G}enome-wide association study ; {BENIN}},
  booktitle = {},
  journal = {{E}biomedicine},
  volume = {82},
  numero = {},
  pages = {104167 [20 ]},
  ISSN = {2352-3964},
  year = {2022},
  DOI = {10.1016/j.ebiom.2022.104167},
  URL = {https://www.documentation.ird.fr/hor/fdi:010085926},
}