Membrane Protein Detection and Morphological Analysis of Red Blood Cells in Hereditary Spherocytosis by Confocal Laser Scanning Microscopy

In hereditary spherocytosis (HS), genetic mutations in the cell membrane and cytoskeleton proteins cause structural defects in red blood cells (RBCs). As a result, cells are rigid and misshapen, usually with a characteristic spherical form (spherocytes), too stiff to circulate through microcirculati...

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Detalles Bibliográficos
Autores: Rey-Barroso L, Roldán M, Burgos-Fernández FJ, Isola I, Ruiz-Llobet A, Gassiot S, Sarrate E, Vilaseca M
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p23207
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=23207
Access Level:acceso abierto
Palabra clave:automated detection
band 3
confocal microscopy
hereditary spherocytosis
immunofluorescence
in-vivo imaging
red blood cells
spherical Hough transform
Descripción
Sumario:In hereditary spherocytosis (HS), genetic mutations in the cell membrane and cytoskeleton proteins cause structural defects in red blood cells (RBCs). As a result, cells are rigid and misshapen, usually with a characteristic spherical form (spherocytes), too stiff to circulate through microcirculation regions, so they are prone to undergo hemolysis and phagocytosis by splenic macrophages. Mild to severe anemia arises in HS, and other derived symptoms like splenomegaly, jaundice, and cholelithiasis. Although abnormally shaped RBCs can be identified under conventional light microscopy, HS diagnosis relies on several clinical factors and sometimes on the results of complex molecular testing. It is specially challenging when other causes of anemia coexist or after recent blood transfusions. We propose two different approaches to characterize RBCs in HS: (i) an immunofluorescence assay targeting protein band 3, which is affected in most HS cases and (ii) a three-dimensional morphology assay, with living cells, staining the membrane with fluorescent dyes. Confocal laser scanning microscopy (CLSM) was used to carry out both assays, and in order to complement the latter, a software was developed for the automated detection of spherocytes in blood samples. CLSM allowed the precise and unambiguous assessment of cell shape and protein expression.