Demonstration of a natural antigalactosyl IgG antibody on thalassemic red blood cells

Abstract

A modified antiglobulin test, based on the high affinity between the Fc portion of the red blood cell (RBC) bound IgG and the Fc receptor on the myeloid cell K-562, was utilized for demonstration of immunoglobulins (Ig) on thalassemic RBC. Ig was found on the RBC of 73 out of 80 patients with thalassemia. The immunoglobulins on the thalassemic RBC belonged to the IgG subclass and were autoreactive. Elution studies utilizing various carbohydrates, or by thermal stripping, indicated that at least part of the IgG molecules found on the thalassemic RBC were specifically reactive with terminal galactosyl residues on the RBC membrane. IgG antibodies with similar reactivity were also demonstrated in normal human serum. These natural antigalactosyl IgG antibodies from normal sera could bind to IgG- depleted thalassemic RBC. Thalassemic RBC and normal senescent RBC were previously found to contain reduced amounts of membrane sialic acid (SA). It is suggested that the antigalactosyl IgG antibodies interact with newly exposed galactosyl residues underlying the sialic acid units. Such interaction may lead to the shortened lifespan of thalassemic RBC and may result in sequestration of senescent normal RBC by the reticuloendothelial system.

Discovery of the natural anti‐Gal antibody and its past and future relevance to medicine

“…In 1983, at the Hadassah Hospital in Jerusalem, I studied the potential role of antibodies in the destruction of red blood cells (RBC) in patients with b-thalassemia. These RBC were found to carry several hundred IgG molecules that could be eluted at 37°C by galactose, but not by other sugars [1]. We further demonstrated the same antibody on RBC in patients with sickle cell anemia [2] and on human senescent RBC [3,4].…”

Erythrocytes with covalently bound fibrinogen as a cellular replacement for the treatment of thrombocytopenia

“…The cellular replacement demonstrated in this study allows one to overcome these limitations. If desirable, the lifespan in the circulation of the fibrinogen-bearing RBCs may be controlled in advance by specific manipulation, such as defined neuroaminidase treatment [26].…”

“…Possible changes in the antigenic properties of the fixed RBCs were monitored by two types of assay. The first was the formation of EA rosettes with K~6 2 [26] cells: this probes for the degree of binding of autologous immunoglobulins to erythrocytes. Control (without cross-linking), mildly or exhaustively cross-linked RBCs, with or without neuroaminidase treatment, do not form any rosettes when incubated in the absence or in the presence of autologous plasma.…”

Erythrocyte Rh antigens increase with red cell age

“…Consequently, it is possible that older more dense cells bind the antibody tightly resulting in reduction of antibody loss due to elution in washing. A similar observation pertaining to the premature expression of the sensecent antigen has been hypothesized as a result of abnormal membrane surface structure in sickle and thalassemic erythrocytes [26,27]. Our findings suggest the possibility of a certain practical approach to transfusion therapy in patients with autoimmune hemolytic anemia in whom the autoantibody has Rh-related specificity.…”