Clearance of pathogenic erythrocytes is maintained despite spleen dysfunction in children with sickle cell disease.

Autor: Sissoko A; Université Paris Cité, Inserm, BIGR, Paris, France., Cissé A; Université Paris Cité, Inserm, BIGR, Paris, France., Duverdier C; Université Paris Cité, Inserm, BIGR, Paris, France., Marin M; Université Paris Cité, Inserm, BIGR, Paris, France., Dumas L; Université Paris Cité, Inserm, BIGR, Paris, France., Manceau S; Laboratoire d'Excellence GR-Ex, Paris, France.; Assistance publique des hôpitaux de Paris, Paris, France., Maître B; Université de Strasbourg, UMR_S1255, INSERM, Établissement Français du Sang-Grand Est, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France., Eckly A; Université de Strasbourg, UMR_S1255, INSERM, Établissement Français du Sang-Grand Est, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France., Fricot-Monsinjon A; Université Paris Cité, Inserm, BIGR, Paris, France., Roussel C; Université Paris Cité, Inserm, BIGR, Paris, France.; Assistance publique des hôpitaux de Paris, Paris, France., Ndour PA; Université Paris Cité, Inserm, BIGR, Paris, France., Dussiot M; Université de Paris, U1163, Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques, INSERM, Paris, France., Dokmak S; Department of HPB surgery and Liver Transplantation, AP-HP, Beaujon Hospital, DMU DIGEST, Clichy, France.; University of Paris Cité, Paris, France., Aussilhou B; Department of HPB surgery and Liver Transplantation, AP-HP, Beaujon Hospital, DMU DIGEST, Clichy, France.; University of Paris Cité, Paris, France., Dembinski J; Department of HPB surgery and Liver Transplantation, AP-HP, Beaujon Hospital, DMU DIGEST, Clichy, France.; University of Paris Cité, Paris, France., Sauvanet A; Department of HPB surgery and Liver Transplantation, AP-HP, Beaujon Hospital, DMU DIGEST, Clichy, France.; University of Paris Cité, Paris, France., Paye F; Assistance publique des hôpitaux de Paris, Paris, France., Lesurtel M; Department of HPB surgery and Liver Transplantation, AP-HP, Beaujon Hospital, DMU DIGEST, Clichy, France.; University of Paris Cité, Paris, France., Cros J; Department of Pathology, Université Paris Cité - FHU MOSAIC, Beaujon Hospital, Clichy, France., Wendum D; AP-HP. Sorbonne Université, Hôpital St Antoine, Paris, France., Tichit M; Histopathology Core Facility, Institut Pasteur, Université Paris Cité, Paris, France., Hardy D; Histopathology Core Facility, Institut Pasteur, Université Paris Cité, Paris, France., Capito C; Assistance publique des hôpitaux de Paris, Paris, France., Allali S; Assistance publique des hôpitaux de Paris, Paris, France.; Reference center for sickle cell disease, Necker-Enfants malades hospital, Paris, France., Buffet P; Université Paris Cité, Inserm, BIGR, Paris, France.; Laboratoire d'Excellence GR-Ex, Paris, France.; Assistance publique des hôpitaux de Paris, Paris, France.; Institut Pasteur, Université Paris Cité, Paris, France.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2024 Dec; Vol. 99 (12), pp. 2267-2278. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1002/ajh.27481
Abstrakt: 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.
(© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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