Yves Colin1, Caroline Le Van Kim, Wassim El Nemer. 1. aInserm U1134 bUniversité Paris Diderot, Sorbonne Paris Cité, UMR_S 1134 cInstitut National de la Transfusion Sanguine dLaboratoire d' Excellence GR-Ex, Paris, France.
Abstract
PURPOSE OF REVIEW: This review discusses the unexpected role of red blood cell (RBC) adhesiveness in the pathophysiology of two red cell diseases, hereditary spherocytosis and polycythemia vera, and two 'nonerythroid' disorders, central retinal vein occlusion and Gaucher disease. These pathologies share common clinical manifestations, that is vaso-occlusion and/or thrombotic events. RECENT FINDINGS: Recently, the direct involvement of RBC adhesion to the vascular endothelium has been demonstrated in the occurrence of vaso-occlusive events, in particular in sickle cell disease (SCD). Several erythroid adhesion molecules and their ligands have been identified that belong to different molecular classes (integrins, Ig-like molecules, lipids...) and are activated by a variety of signaling pathways. Among these, the laminin receptor, Lutheran/basal cell adhesion molecule, which is activated by phosphorylation, appears to play a central role in several pathologies. SUMMARY: RBC adhesiveness might be involved in complications such as the vaso-occlusive crisis in SCD, thrombosis in polycythemia vera, splenic sequestration in hereditary spherocytosis, occlusions in central retinal vein occlusion and bone infarcts in Gaucher disease. Characterization of this pathological process at the cellular and molecular levels should prove useful to develop new therapeutic approaches based on the blockade of RBC abnormal interactions with vascular endothelium and/or circulating blood cells.
PURPOSE OF REVIEW: This review discusses the unexpected role of red blood cell (RBC) adhesiveness in the pathophysiology of two red cell diseases, hereditary spherocytosis and polycythemia vera, and two 'nonerythroid' disorders, central retinal vein occlusion and Gaucher disease. These pathologies share common clinical manifestations, that is vaso-occlusion and/or thrombotic events. RECENT FINDINGS: Recently, the direct involvement of RBC adhesion to the vascular endothelium has been demonstrated in the occurrence of vaso-occlusive events, in particular in sickle cell disease (SCD). Several erythroid adhesion molecules and their ligands have been identified that belong to different molecular classes (integrins, Ig-like molecules, lipids...) and are activated by a variety of signaling pathways. Among these, the laminin receptor, Lutheran/basal cell adhesion molecule, which is activated by phosphorylation, appears to play a central role in several pathologies. SUMMARY: RBC adhesiveness might be involved in complications such as the vaso-occlusive crisis in SCD, thrombosis in polycythemia vera, splenic sequestration in hereditary spherocytosis, occlusions in central retinal vein occlusion and bone infarcts in Gaucher disease. Characterization of this pathological process at the cellular and molecular levels should prove useful to develop new therapeutic approaches based on the blockade of RBC abnormal interactions with vascular endothelium and/or circulating blood cells.
Authors: Nathalie Chami; Ming-Huei Chen; Andrew J Slater; John D Eicher; Evangelos Evangelou; Salman M Tajuddin; Latisha Love-Gregory; Tim Kacprowski; Ursula M Schick; Akihiro Nomura; Ayush Giri; Samuel Lessard; Jennifer A Brody; Claudia Schurmann; Nathan Pankratz; Lisa R Yanek; Ani Manichaikul; Raha Pazoki; Evelin Mihailov; W David Hill; Laura M Raffield; Amber Burt; Traci M Bartz; Diane M Becker; Lewis C Becker; Eric Boerwinkle; Jette Bork-Jensen; Erwin P Bottinger; Michelle L O'Donoghue; David R Crosslin; Simon de Denus; Marie-Pierre Dubé; Paul Elliott; Gunnar Engström; Michele K Evans; James S Floyd; Myriam Fornage; He Gao; Andreas Greinacher; Vilmundur Gudnason; Torben Hansen; Tamara B Harris; Caroline Hayward; Jussi Hernesniemi; Heather M Highland; Joel N Hirschhorn; Albert Hofman; Marguerite R Irvin; Mika Kähönen; Ethan Lange; Lenore J Launer; Terho Lehtimäki; Jin Li; David C M Liewald; Allan Linneberg; Yongmei Liu; Yingchang Lu; Leo-Pekka Lyytikäinen; Reedik Mägi; Rasika A Mathias; Olle Melander; Andres Metspalu; Nina Mononen; Mike A Nalls; Deborah A Nickerson; Kjell Nikus; Chris J O'Donnell; Marju Orho-Melander; Oluf Pedersen; Astrid Petersmann; Linda Polfus; Bruce M Psaty; Olli T Raitakari; Emma Raitoharju; Melissa Richard; Kenneth M Rice; Fernando Rivadeneira; Jerome I Rotter; Frank Schmidt; Albert Vernon Smith; John M Starr; Kent D Taylor; Alexander Teumer; Betina H Thuesen; Eric S Torstenson; Russell P Tracy; Ioanna Tzoulaki; Neil A Zakai; Caterina Vacchi-Suzzi; Cornelia M van Duijn; Frank J A van Rooij; Mary Cushman; Ian J Deary; Digna R Velez Edwards; Anne-Claire Vergnaud; Lars Wallentin; Dawn M Waterworth; Harvey D White; James G Wilson; Alan B Zonderman; Sekar Kathiresan; Niels Grarup; Tõnu Esko; Ruth J F Loos; Leslie A Lange; Nauder Faraday; Nada A Abumrad; Todd L Edwards; Santhi K Ganesh; Paul L Auer; Andrew D Johnson; Alexander P Reiner; Guillaume Lettre Journal: Am J Hum Genet Date: 2016-06-23 Impact factor: 11.025