Splenectomy prolongs in vivo survival of erythrocytes differently in spectrin/ankyrin- and band 3-deficient hereditary spherocytosis.
Red cell (RBC) deformability and membrane-bound immunoglobulin G (IgG) were studied to better understand premature clearance of erythrocytes in hereditary spherocytosis. Averaged deformability profiles from cells having comparable cell age revealed that splenectomy was more beneficial for spectrin/ankyrin-deficient than for band 3-deficient RBCs. Splenectomy prevented an early loss of young cells in both types of deficiencies. It had an additional beneficial effect on spectrin/ankyrin-deficient but not band 3-deficient RBCs. It prolonged the survival of mature spectrin/ankyrin-deficient RBCs such that they lost their deformability more slowly than RBCs from patients who had not undergone splenectomy. Band 3-deficient RBCs lost their deformability at the same rate before and after splenectomy. In HS patients with band 3 deficiency who underwent splenectomy, RBC deformability inversely correlated with the number of RBC-bound IgG (up to 140 molecules per cell). In spectrin/ankyrin deficiency, RBC-bound IgG remained at control levels (60 IgG or less per cell). It appears that spectrin/ankyrin-deficient RBCs escaped opsonization by releasing band 3-containing vesicles because their band 3 content and deformability dropped in parallel with increasing cell age. Band 3-deficient RBCs did not lose band 3 with increasing cell age. Hence, it is possible that band 3 clusters required for bivalent binding of low-affinity-IgG, naturally occurring antibodies were retained in band 3-deficient RBCs with a relative excess of skeletal proteins but were released from spectrin/ankyrin-deficient RBCs, in which vesicle budding was facilitated by an impaired skeleton.
Institute of Biochemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg HPM D14.2, CH 8093 Zurich, Switzerland.
Ramune
R
Reliene
Mariagabriella
M
Mariani
Alberto
A
Zanella
Walter H
WH
Reinhart
M Leticia
ML
Ribeiro
Emanuele Miraglia
EM
del Giudice
Silverio
S
Perrotta
Achille
A
Iolascon
Stefan
S
Eber
Hans U
HU
Lutz
D001457:Anion Exchange Protein 1, Erythrocyte / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017487:Ankyrins / Q000172:deficiency; D016022:Case-Control Studies; D002470:Cell Survival; D004905:Erythrocyte Aging / Q000502:physiology*; D004907:Erythrocyte Deformability; D004912:Erythrocytes / Q000737:chemistry / Q000166:cytology*; D005192:Family Health; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D013049:Spectrin / Q000172:deficiency; D013103:Spherocytosis, Hereditary / Q000097:blood* / Q000209:etiology / Q000601:surgery*; D013156:Splenectomy; D016896:Treatment Outcome
D001457:Anion Exchange Protein 1, Erythrocyte; D017487:Ankyrins; D007074:Immunoglobulin G; D008565:Membrane Proteins; D013049:Spectrin