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.