Henry B., Volle G., Akpovi H., Gineau L., Roussel C., Ndour P. A., Tossou F., Suarez F., Palstra F., Fricot A., Chambrion C., Solinc J., Nguyen J., Gare M., Aussenac F., Cottart C. H., Keyser C., Adamou R., Tichit M., Hardy D., Fievet Nadine, Clain J., Garcia André, Courtin David, Hermine O., Sabbagh A., Buffet P. (2022). Splenic clearance of rigid erythrocytes as an inherited mechanism for splenomegaly and natural resistance to malaria. Ebiomedicine, 82, 104167 [20 p.]. ISSN 2352-3964.
Titre du document
Splenic clearance of rigid erythrocytes as an inherited mechanism for splenomegaly and natural resistance to malaria
Année de publication
2022
Auteurs
Henry B., Volle G., Akpovi H., Gineau L., Roussel C., Ndour P. A., Tossou F., Suarez F., Palstra F., Fricot A., Chambrion C., Solinc J., Nguyen J., Gare M., Aussenac F., Cottart C. H., Keyser C., Adamou R., Tichit M., Hardy D., Fievet Nadine, Clain J., Garcia André, Courtin David, Hermine O., Sabbagh A., Buffet P.
Source
Ebiomedicine, 2022,
82, 104167 [20 p.] ISSN 2352-3964
Background In malaria-endemic areas, subjects from specific groups like Fulani have a peculiar protection against malaria, with high levels of IgM but also frequent anaemia and splenomegaly. The mechanisms underlying this phenotype remain elusive. Methods In a cohort study set up in Benin, West Africa, after a careful evaluation of malaria-related phenotypes, we measured the deformability of circulating erythrocytes in genetically distinct groups (including Fulani) living in sympatry, using ektacytometry and microsphiltration, a mimic of how the spleen clears rigid erythrocytes. Heritability of erythrocytes deformability was calculated, followed by a genome-wide association study (GWAS) of the same phenotype. Findings Compared to non-Fulani, Fulani displayed a higher deformability of circulating erythrocytes, pointing to an enhanced clearance of rigid erythrocytes by the spleen. This phenotype was observed in individuals displaying markers of Plasmodium falciparum infection. The heritability of this new trait was high, with a strong multigenic component. Five 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, PDE10A), through control of vascular tone, collagen synthesis and macrophage activity. Interpretation In 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-IgM, and partial protection against malaria. Beyond malaria-related phenotypes, inherited splenic hyper-filtration of erythrocytes may impact the pathogenesis of other hematologic diseases.
Plan de classement
Santé : généralités [050]
;
Entomologie médicale / Parasitologie / Virologie [052]
Description Géographique
BENIN
Localisation
Fonds IRD [F B010085926]
Identifiant IRD
fdi:010085926
