Clearance of pathogenic erythrocytes is maintained despite spleen dysfunction in children with sickle cell disease
Abdoulaye Sissoko
(1)
,
Astan Cissé
(1)
,
Clémence Duverdier
(1)
,
Mickaël Marin
(1)
,
Lucie Dumas
(1)
,
Sandra Manceau
(2, 3)
,
Blandine Maître
(4, 5, 6)
,
Anita Eckly
(4, 5, 6)
,
Aurélie Fricot-Monsinjon
(1)
,
Camille Roussel
(1, 3)
,
Papa Alioune Ndour
(1)
,
Michael Dussiot
(7)
,
Safi Dokmak
(8, 9)
,
Béatrice Aussilhou
(8, 9)
,
Jeanne Dembinski
(8, 9)
,
Alain Sauvanet
(8, 9)
,
François Paye
(3)
,
Mickaël Lesurtel
(8, 9)
,
Jérôme Cros
(8, 9)
,
Dominique Wendum
(10, 11)
,
Magali Tichit
(12)
,
David Hardy
(12)
,
Carmen Capito
(3)
,
Slimane Allali
(13)
,
Pierre Buffet
(1, 2, 3, 14)
1
BIGR (UMR_S_1134 / U1134) -
Biologie Intégrée du Globule Rouge
2 Labex Gr-Ex - Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge
3 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
4 BPPS - Biologie et Pharmacologie des Plaquettes sanguines : hémostase, thrombose, transfusion
5 FMTS - Fédération de Médecine Translationnelle de Strasbourg
6 EFS - alsace strasbourg - Etablissement Français du Sang - Grand Est
7 ERL 8254 - Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications
8 Hôpital Beaujon [AP-HP]
9 UPCité - Université Paris Cité
10 CHU Saint-Antoine [AP-HP]
11 SU - Sorbonne Université
12 Plate-Forme d’Histopathologie / Histopathology Platform
13 Hôpital Necker - Enfants Malades [AP-HP]
14 IP - Institut Pasteur [Paris]
2 Labex Gr-Ex - Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge
3 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
4 BPPS - Biologie et Pharmacologie des Plaquettes sanguines : hémostase, thrombose, transfusion
5 FMTS - Fédération de Médecine Translationnelle de Strasbourg
6 EFS - alsace strasbourg - Etablissement Français du Sang - Grand Est
7 ERL 8254 - Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications
8 Hôpital Beaujon [AP-HP]
9 UPCité - Université Paris Cité
10 CHU Saint-Antoine [AP-HP]
11 SU - Sorbonne Université
12 Plate-Forme d’Histopathologie / Histopathology Platform
13 Hôpital Necker - Enfants Malades [AP-HP]
14 IP - Institut Pasteur [Paris]
Abdoulaye Sissoko
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 1167681
- ORCID : 0000-0002-9986-0494
Connectez-vous pour contacter l'auteur
Mickaël Marin
- Fonction : Auteur
- PersonId : 1439421
- ORCID : 0000-0002-4094-022X
Jeanne Dembinski
- Fonction : Auteur
- PersonId : 1151805
- ORCID : 0000-0002-9242-6038
- IdRef : 260091405
Magali Tichit
- Fonction : Auteur
- PersonId : 911185
David Hardy
- Fonction : Auteur
- PersonId : 734733
- IdHAL : david-hardy
- ORCID : 0000-0001-5874-4377
Slimane Allali
- Fonction : Auteur
- PersonId : 1167682
- ORCID : 0000-0001-7068-4530
Résumé
In children with sickle cell disease (SCD), splenectomy is immediately beneficial for acute sequestration crises and hypersplenism (ASSC/HyS) but portends a long‐term risk of asplenia‐related complications. We retrieved peripheral and splenic red blood cells (RBCs) from 17 SCD children/teenagers undergoing partial splenectomy for ASSC/HyS, 12 adult subjects without RBC‐related disease undergoing splenectomy (controls), five human spleens perfused ex vivo with Hb SS ‐ and Hb AA ‐RBC, and quantified abnormal RBC by microscopy, spleen‐mimetic RBC filtration, and adhesion assays. Spleens were analyzed by immunohistochemistry and transmission electron microscopy (TEM). In circulating blood of SCD and control subjects, dysmorphic (elongated/spherocytic) RBCs were <2%, while proportions of pocked‐RBC were 4.3‐fold higher in SCD children than in controls. Compared to controls, splenic RBCs were more frequently dysmorphic (29.3% vs. 0.4%), stiffer (42.2% vs. 12.4%), and adherent (206 vs. 22 adherent RBC/area) in SCD subjects. By TEM, both polymer‐containing and homogenous RBC contributed to spleen congestion, resulting in 3.8‐fold higher RBC population density in SCD spleens than in control spleens, predominantly in the cords. Perfused spleens with normal function displayed similar congestion and retention of dysmorphic RBC as SCD spleens. The population density of active macrophages was similar in SCD and control spleens, with a relative deficit in phagocytosis of polymer‐containing RBC. Despite the existence of hyposplenism, splenectomy in SCD children removes an organ that still efficiently filters out potentially pathogenic altered RBC. Innovative treatments allowing fine‐tuned reduction of RBC retention would alleviate spleen congestion, the major pathogenic process in ASSC/HyS, while preserving spleen protective functions for the future.
Domaines
Sciences du Vivant [q-bio]| Format du dépôt | Fichier |
|---|---|
| Type de dépôt | Article dans une revue |
| Titre |
en
Clearance of pathogenic erythrocytes is maintained despite spleen dysfunction in children with sickle cell disease
|
| Résumé |
en
In children with sickle cell disease (SCD), splenectomy is immediately beneficial for acute sequestration crises and hypersplenism (ASSC/HyS) but portends a long‐term risk of asplenia‐related complications. We retrieved peripheral and splenic red blood cells (RBCs) from 17 SCD children/teenagers undergoing partial splenectomy for ASSC/HyS, 12 adult subjects without RBC‐related disease undergoing splenectomy (controls), five human spleens perfused ex vivo with Hb SS ‐ and Hb AA ‐RBC, and quantified abnormal RBC by microscopy, spleen‐mimetic RBC filtration, and adhesion assays. Spleens were analyzed by immunohistochemistry and transmission electron microscopy (TEM). In circulating blood of SCD and control subjects, dysmorphic (elongated/spherocytic) RBCs were <2%, while proportions of pocked‐RBC were 4.3‐fold higher in SCD children than in controls. Compared to controls, splenic RBCs were more frequently dysmorphic (29.3% vs. 0.4%), stiffer (42.2% vs. 12.4%), and adherent (206 vs. 22 adherent RBC/area) in SCD subjects. By TEM, both polymer‐containing and homogenous RBC contributed to spleen congestion, resulting in 3.8‐fold higher RBC population density in SCD spleens than in control spleens, predominantly in the cords. Perfused spleens with normal function displayed similar congestion and retention of dysmorphic RBC as SCD spleens. The population density of active macrophages was similar in SCD and control spleens, with a relative deficit in phagocytosis of polymer‐containing RBC. Despite the existence of hyposplenism, splenectomy in SCD children removes an organ that still efficiently filters out potentially pathogenic altered RBC. Innovative treatments allowing fine‐tuned reduction of RBC retention would alleviate spleen congestion, the major pathogenic process in ASSC/HyS, while preserving spleen protective functions for the future.
|
| Auteur(s) |
Abdoulaye Sissoko
1
, Astan Cissé
1
, Clémence Duverdier
1
, Mickaël Marin
1
, Lucie Dumas
1
, Sandra Manceau
2, 3
, Blandine Maître
4, 5, 6
, Anita Eckly
4, 5, 6
, Aurélie Fricot-Monsinjon
1
, Camille Roussel
1, 3
, Papa Alioune Ndour
1
, Michael Dussiot
7
, Safi Dokmak
8, 9
, Béatrice Aussilhou
8, 9
, Jeanne Dembinski
8, 9
, Alain Sauvanet
8, 9
, François Paye
3
, Mickaël Lesurtel
8, 9
, Jérôme Cros
8, 9
, Dominique Wendum
10, 11
, Magali Tichit
12
, David Hardy
12
, Carmen Capito
3
, Slimane Allali
13
, Pierre Buffet
1, 2, 3, 14
1
BIGR (UMR_S_1134 / U1134) -
Biologie Intégrée du Globule Rouge
( 1005032 )
- 6 rue Alexandre Cabanel - 75739 Paris cedex 15
- France
2
Labex Gr-Ex -
Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge
( 1005049 )
- Imagine Institute
24, Boulevard du Montparnasse
75015, Paris
- France
3
AP-HP -
Assistance publique - Hôpitaux de Paris (AP-HP)
( 300068 )
- France
4
BPPS -
Biologie et Pharmacologie des Plaquettes sanguines : hémostase, thrombose, transfusion
( 543251 )
- Établissement français du sang (EFS Alsace)
10 rue Spielmann - BP 36
67065 Strasbourg Cedex
- France
5
FMTS -
Fédération de Médecine Translationnelle de Strasbourg
( 528325 )
- Faculté de médecine
4 rue Kirschleger, 67000 Strasbourg
- France
6
EFS - alsace strasbourg -
Etablissement Français du Sang - Grand Est
( 537675 )
- 10 rue Spielmann - 67000 Strasbourg
- France
7
ERL 8254 -
Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications
( 1004684 )
- Institut Imagine, 24 Boulevard de Montparnasse, 75015 PARIS
- France
8
Hôpital Beaujon [AP-HP]
( 300983 )
- 100, boulevard du Général Leclerc 92 Clichy
- France
9
UPCité -
Université Paris Cité
( 557826 )
- 85 boulevard Saint-Germain
75006 Paris
- France
10
CHU Saint-Antoine [AP-HP]
( 454982 )
- 184, rue du Faubourg Saint-Antoine
75571 Paris cedex 12
- France
11
SU -
Sorbonne Université
( 413221 )
- 21 rue de l’École de médecine - 75006 Paris
- France
12
Plate-Forme d’Histopathologie / Histopathology Platform
( 1094910 )
- 25-28 rue du Docteur Roux - 75015 Paris
- France
13
Hôpital Necker - Enfants Malades [AP-HP]
( 414766 )
- 149 Rue de Sèvres 75015 Paris
- France
14
IP -
Institut Pasteur [Paris]
( 300027 )
- 25-28, rue du docteur Roux, 75724 Paris cedex 15
- France
|
| Vulgarisation |
Non
|
| Comité de lecture |
Oui
|
| Audience |
Internationale
|
| Langue du document |
Anglais
|
| Nom de la revue |
|
| Volume |
99
|
| Numéro |
12
|
| Page/Identifiant |
2267-2278
|
| Licence |
Paternité - Pas d'utilisation commerciale - Pas de modification
|
| Date de publication |
2024-12
|
| Domaine(s) |
|
| Projet(s) ANR |
|
| Financement |
|
| Collaboration/Projet |
|
| DOI | 10.1002/ajh.27481 |
| Pubmed Id | 39286963 |
Fichier principal
American J Hematol - 2024 - Sissoko - Clearance of pathogenic erythrocytes is maintained despite spleen dysfunction in.pdf ( 3.2 Mo
)
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Origine :
Publication financée par une institution
Licence :
Paternité - Pas d'utilisation commerciale - Pas de modification
- CC BY 4.0
Licence :
Paternité - Pas d'utilisation commerciale - Pas de modification
- CC BY 4.0
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