Non-opsonising aggregates of IgG and complement in haemoglobin C erythrocytes

SummaryHaemoglobin C (HbC) differs from normal HbA by a lysine for glutamatesubstitution at position 6 of beta-globin. Heterozygous AC and homozygousCC phenotypes are associated with shortened erythrocyte life spans and mildanaemia. AC and CC erythrocytes contain elevated amounts of membrane-associated haemichromes, band 3 clusters, and immunoglobulin G (IgG)in vivo. These findings led us to investigate whether AC and CC erythrocytesmight expose elevated levels of IgG and complement, two opsonins that havebeen implicated in the phagocytic clearance of senescent and sickleerythrocytes. Surprisingly, we found IgG, complement, and other plasmaproteins co-localised in aggregates beneath the membrane of circulating ACand CC erythrocytes. These observations, and our finding of similaraggregates in erythrocytes heterozygous or homozygous for haemoglobin S(sickle-cell haemoglobin), suggest that the vast majority of membrane-associated IgG and complement detected in these abnormal erythrocytes isintracellular and does not contribute to the eventual opsonic clearance ofthese cells. Phagocytosis studies with macrophages provide evidence insupport of this suggestion. Studies of erythrocyte clearance that involve thedetection of membrane-associated IgG and complement as putative opsoninsshould investigate the possibility that these plasma proteins reside in theerythrocyte interior, and not on the cell surface.Keywords: haemoglobin C, haemoglobin S, sickle cell, erythrocyte senes-cence, autologous IgG.