Red cell autoantibodies, multiple immunoglobulin classes, and autoimmune hemolysis

Abstract

The effects and interrelationships of multiple immunoglobulin coating (i.e., increased red cell [RBC]-bound IgM and/or IgA in addition to IgG) were investigated in 404 patients with warm-reactive RBC autoantibodies on 590 occasions. Multiple immunoglobulins were detected by enzyme-linked direct antiglobulin tests in 218 samples (37%), but in only 87 (15%) by agglutination methods. Differences in populations were examined by chi-square, with p less than 0.005 being required for significance because of the multiple tests. Compared with IgG coating alone, multiple immunoglobulins were significantly associated with larger quantities (greater than 800 molecules/RBC) of IgG, multiple IgG subclasses, IgG3 and C3d bound to the cells, and with serum haptoglobin levels of less than 0.1 g per L. The latter association was still significant when higher levels of RBC-bound IgG and subclass pattern were taken into account. In samples with multiple immunoglobulin coating, there was no significant relationship (p greater than 0.05) between haptoglobins of less than 0.1 g per L and either C3d or multiple IgG subclasses. It was concluded that multiple immunoglobulin coating, even when undetected by agglutination methods, is a major cause of hemolysis: it is part of a more generalized autoimmune response and acts with other factors such as the quantity of bound IgG, the IgG subclass pattern, and complement; it also has an important hemolytic effect in its own right.

Intensive plasma exchange for severe autoimmune hemolytic anemia in a four-month-old infant

“…Severely anemic patients are usually symptomatic and require RBC transfusions [18]. Usually, crossmatchcompatible RBCs cannot be found and "least incompatible" units will be transfused [5,14,15,16,17,20].…”

A Quantitative ELISA for Measuring Red Cell-Bound Immunoglobulins

“…1). As the patient samples were selected on the basis of a posi tive direct antiglobulin test for IgG, the presence of raised IgA levels in some of them was not surprising in view of the known occurrence of multiple immunoglobulin coat ing of red cells in autoimmune haemolysis; it has been reported that about 14% of patients with increased amounts of cell-bound IgG also have increased amounts of cell-bound IgA and, in some cases, IgM [ 1,3]. It is perti nent that the seven highest IgA values obtained here (116-4,500 molecules per cell) were on the specimens which had shown increased amounts of IgA on the routine test, 2 patients having autoimmune haemolytic anaemia, 3 myelodysplastic syndrome, 1 chronic lymphocytic leu kaemia and 1 rheumatoid arthritis.…”

“…In patients with autoimmune haemolytic disease, the relationship between the immunoproteins bound to the red cells and the degree of in vivo haemolysis is a complex one [1][2][3]. To elucidate this relationship further, a satis factory quantitative method for determining the levels of the different immunoproteins would be invaluable.…”

Immune hemolysis-serological and clinical aspects

“…These include hereditary hemolytic anemias, paroxysmal nocturnal hemoglobinuria, microangiopathic hemolytic disorders, aplastic anemia, megaloblastic anemia, and anemias associated with many other disorders. The following hemolytic anemias are sometimes difficult to differentiate from AIHA of the warm type by serological testing: drug-induced toxic or immune hemolysis, hemolytic transfusion reactions (particularly those associated with transfusion-induced autoantibodies of RBCs), pregnancy associated autoantibodies to RBCs, paroxysmal cold hemoglobinuria, AIHA of cold type, particularly those related to antibodies with high temperature amplitudes [35][36][37], and most importantly all types of immune hemolytic anemias related to transient lymphocyte syndrome secondary to solid organ or bone marrow transplantation [38,39].…”