TEAM MEMBER

Aurélie Fricot

Engineer, Spleen function in physiology and disease group

aurelie.fricot@inserm.fr

Rapid clearance of storage-induced microerythrocytes alters transfusion recovery.

Roussel Camille*, Morel Alexandre*, Dussiot Michaël*, Marin Mickaël, Colard Martin, Fricot-Monsinjon Aurélie, Martinez Anaïs, Chambrion Charlotte, Henry Benoît, Casimir Madeleine, Volle Geoffroy, Dépond Mallorie, Dokmak Safi, Paye François, Sauvanet Alain, Le Van Kim Caroline, Colin Yves, Georgeault Sonia, Roingeard Philippe, Spitalnik Steven L, Ndour Papa Alioune, Hermine Olivier, Hod Eldad A, Buffet Pierre A**, Amireault Pascal**
Blood, 137 (2021) 

Permanent availability of red blood cells (RBCs) for transfusion depends on refrigerated storage, during which morphologically altered RBCs accumulate. Among these, a subpopulation of small RBCs, comprising type III echinocytes, spheroechinocytes, and spherocytes and defined as storage-induced microerythrocytes (SMEs), could be rapidly cleared from circulation posttransfusion. We quantified the proportion of SMEs in RBC concentrates from healthy human volunteers and assessed correlation with transfusion recovery, investigated the fate of SMEs upon perfusion through human spleen ex vivo, and explored where and how SMEs are cleared in a mouse model of blood storage and transfusion. In healthy human volunteers, high proportion of SMEs in long-stored RBC concentrates correlated with poor transfusion recovery. When perfused through human spleen, 15% and 61% of long-stored RBCs and SMEs were cleared in 70 minutes, respectively. High initial proportion of SMEs also correlated with high retention of RBCs by perfused human spleen. In the mouse model, SMEs accumulated during storage. Transfusion of long-stored RBCs resulted in reduced posttransfusion recovery, mostly due to SME clearance. After transfusion in mice, long-stored RBCs accumulated predominantly in spleen and were ingested mainly by splenic and hepatic macrophages. In macrophage-depleted mice, splenic accumulation and SME clearance were delayed, and transfusion recovery was improved. In healthy hosts, SMEs were cleared predominantly by macrophages in spleen and liver. When this well-demarcated subpopulation of altered RBCs was abundant in RBC concentrates, transfusion recovery was diminished. SME quantification has the potential to improve blood product quality assessment. This trial was registered at www.clinicaltrials.gov as #NCT02889133.

Blood, 2021, vol.137, p.

Roussel Camille*, Morel Alexandre*, Dussiot Michaël*, Marin Mickaël, Colard Martin, Fricot-Monsinjon Aurélie, Martinez Anaïs, Chambrion Charlotte, Henry Benoît, Casimir Madeleine, Volle Geoffroy, Dépond Mallorie, Dokmak Safi, Paye François, Sauvanet Alain, Le Van Kim Caroline, Colin Yves, Georgeault Sonia, Roingeard Philippe, Spitalnik Steven L, Ndour Papa Alioune, Hermine Olivier, Hod Eldad A, Buffet Pierre A**, Amireault Pascal**

Hidden Biomass of Intact Malaria Parasites in the Human Spleen.

Kho Steven, Qotrunnada Labibah, Leonardo Leo, Andries Benediktus, Wardani Putu A I, Fricot Aurelie, Henry Benoit, Hardy David, Margyaningsih Nur I, Apriyanti Dwi, Puspitasari Agatha M, Prayoga Pak, Trianty Leily, Kenangalem Enny, Chretien Fabrice, Safeukui Innocent, Del Portillo Hernando A, Fernandez-Becerra Carmen, Meibalan Elamaran, Marti Matthias, Price Ric N, Woodberry Tonia, Ndour Papa A, Russell Bruce M, Yeo Tsin W, Minigo Gabriela, Noviyanti Rintis, Poespoprodjo Jeanne R, Siregar Nurjati C, Buffet Pierre A*, Anstey Nicholas M*
The New England journal of medicine, 384 (2021) 

The New England journal of medicine, 2021, vol.384, p.

Kho Steven, Qotrunnada Labibah, Leonardo Leo, Andries Benediktus, Wardani Putu A I, Fricot Aurelie, Henry Benoit, Hardy David, Margyaningsih Nur I, Apriyanti Dwi, Puspitasari Agatha M, Prayoga Pak, Trianty Leily, Kenangalem Enny, Chretien Fabrice, Safeukui Innocent, Del Portillo Hernando A, Fernandez-Becerra Carmen, Meibalan Elamaran, Marti Matthias, Price Ric N, Woodberry Tonia, Ndour Papa A, Russell Bruce M, Yeo Tsin W, Minigo Gabriela, Noviyanti Rintis, Poespoprodjo Jeanne R, Siregar Nurjati C, Buffet Pierre A*, Anstey Nicholas M*

Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: A prospective human splenectomy study.

Kho Steven, Qotrunnada Labibah, Leonardo Leo, Andries Benediktus, Wardani Putu A I, Fricot Aurelie, Henry Benoit, Hardy David, Margyaningsih Nur I, Apriyanti Dwi, Puspitasari Agatha M, Prayoga Pak, Trianty Leily, Kenangalem Enny, Chretien Fabrice, Brousse Valentine, Safeukui Innocent, Del Portillo Hernando A, Fernandez-Becerra Carmen, Meibalan Elamaran, Marti Matthias, Price Ric N, Woodberry Tonia, Ndour Papa A, Russell Bruce M, Yeo Tsin W, Minigo Gabriela, Noviyanti Rintis, Poespoprodjo Jeanne R, Siregar Nurjati C, Buffet Pierre A*, Anstey Nicholas M*
PLoS medicine, 18 (2021) 

[A very large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human individuals infected with Plasmodium vivax. The mechanisms underlying this intense tropism are not clear. We hypothesised that immature reticulocytes, in which P. vivax develops, may display high densities in the spleen, thereby providing a niche for parasite survival.,We examined spleen tissue in 22 mostly untreated individuals naturally exposed to P. vivax and Plasmodium falciparum undergoing splenectomy for any clinical indication in malaria-endemic Papua, Indonesia (2015 to 2017). Infection, parasite and immature reticulocyte density, and splenic distribution were analysed by optical microscopy, flow cytometry, and molecular assays. Nine non-endemic control spleens from individuals undergoing spleno-pancreatectomy in France (2017 to 2020) were also examined for reticulocyte densities. There were no exclusion criteria or sample size considerations in both patient cohorts for this demanding approach. In Indonesia, 95.5% (21/22) of splenectomy patients had asymptomatic splenic Plasmodium infection (7 P. vivax, 13 P. falciparum, and 1 mixed infection). Significant splenic accumulation of immature CD71 intermediate- and high-expressing reticulocytes was seen, with concentrations 11 times greater than in peripheral blood. Accordingly, in France, reticulocyte concentrations in the splenic effluent were higher than in peripheral blood. Greater rigidity of reticulocytes in splenic than in peripheral blood, and their higher densities in splenic cords both suggest a mechanical retention process. Asexual-stage P. vivax-infected erythrocytes of all developmental stages accumulated in the spleen, with non-phagocytosed parasite densities 3,590 times (IQR: 2,600 to 4,130) higher than in circulating blood, and median total splenic parasite loads 81 (IQR: 14 to 205) times greater, accounting for 98.7% (IQR: 95.1% to 98.9%) of the estimated total-body P. vivax biomass. More reticulocytes were in contact with sinus lumen endothelial cells in P. vivax- than in P. falciparum-infected spleens. Histological analyses revealed 96% of P. vivax rings/trophozoites and 46% of schizonts colocalised with 92% of immature reticulocytes in the cords and sinus lumens of the red pulp. Larger splenic cohort studies and similar investigations in untreated symptomatic malaria are warranted.,Immature CD71+ reticulocytes and splenic P. vivax-infected erythrocytes of all asexual stages accumulate in the same splenic compartments, suggesting the existence of a cryptic endosplenic lifecycle in chronic P. vivax infection. Findings provide insight into P. vivax-specific adaptions that have evolved to maximise survival and replication in the spleen.]

PLoS medicine, 2021, vol.18, p.

Kho Steven, Qotrunnada Labibah, Leonardo Leo, Andries Benediktus, Wardani Putu A I, Fricot Aurelie, Henry Benoit, Hardy David, Margyaningsih Nur I, Apriyanti Dwi, Puspitasari Agatha M, Prayoga Pak, Trianty Leily, Kenangalem Enny, Chretien Fabrice, Brousse Valentine, Safeukui Innocent, Del Portillo Hernando A, Fernandez-Becerra Carmen, Meibalan Elamaran, Marti Matthias, Price Ric N, Woodberry Tonia, Ndour Papa A, Russell Bruce M, Yeo Tsin W, Minigo Gabriela, Noviyanti Rintis, Poespoprodjo Jeanne R, Siregar Nurjati C, Buffet Pierre A*, Anstey Nicholas M*