Increased IgG molecules bound to the surface of red blood cells of patients with sickle cell anemia

Abstract

We have used the complement-fixing antibody consumption ( CFAC ) test to detect small concentrations of IgG on red blood cells from patients with hemolytic anemias that are not thought to be caused by an immune mechanism. Although patients with hereditary spherocytosis, pyruvate kinase deficiency, and mechanical hemolytic anemias generally had normal concentrations of IgG bound to their red cells (less than 25 molecules IgG per red cell), we found that 39/62 (63%) patients with sickle cell anemia had elevated values. These 39 patients had a mean of 195 and a maximum of 890 molecules of IgG per red cell. None of the patients had been transfused within the previous 90 days, and some had never been transfused. Direct antiglobulin tests were positive in only two instances and autoantibodies were not found in the serum of any patient. However, eluates from the red cells of 6 of 23 patients demonstrated antibody activity against all of a panel of normal red cells by the indirect antiglobulin test. There was no correlation between the number of IgG molecules on patients' red cells and the severity of their anemia, the incidence of painful sickle cell crises, the reticulocyte count, or with blood transfusion history. We conclude that further study of immunohematologic abnormalities in patients with sickle cell anemia is warranted, especially in view of previous reports in this population of patients with red cell autoantibodies, autoimmune hemolytic anemia, hemolytic transfusion reactions without detectable alloantibodies, and an association of some episodes of pain crises with immunologically mediated red cell destruction.

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

“…We concluded from our data that the vast majority of IgG and complement associated with AC and CC erythrocytes is intracellular and does not accelerate the opsonic removal of these cells. Our findings contrast with those reported for sickled erythrocytes (Petz et al, 1984;Green et al, 1985;Waugh et al, 1986;Kannan et al, 1988;Green, 1993Green, , 1996. Elevated levels of haemichromes, autologous IgG, and complement, and increased erythrophagocytosis by peripheral blood macrophages in vitro, have implicated IgG in the premature removal of SS erythrocytes in vivo.…”

Erythrocyte autoantibodies in paediatric patients with sickle cell disease receiving transfusion therapy: frequency, characteristics and significance

“…Repeated deformation of the erythrocyte membrane and abnormal interactions with the endothelium may lead to exposure of erythrocyte neoantigens that induce IgG autoantibody formation (Kay, 1978). Increased amounts of surface-bound IgG have been detected on the erythrocytes of patients with sickle cell disease (Petz et al, 1984), suggesting that the abnormal erythrocytes themselves contribute directly to the formation of autoantibodies. Exposure of inner leaflet phospholipid components also can lead to deposition of surface complement via activation of the alternative pathway (Wang et al, 1993).…”

Immunoregulation of Cellular Life Span

“…Besides their role in the removal of senescent and damaged cells, antibodies to band 3 also appear to be involved in the removal of erythrocytes in clinical hemolytic anemias 51,83,84 and sickle cell anemia, [85][86][87][88] and the removal of malaria-infected erythrocytes [68][69][70]89 and stored cells. 8,10,13,90 Since oxidation generates senescent cell antigen in situ, 18 it may have contributed to red cell damage in these situations.…”