Red cell autoantibodies, multiple immunoglobulin classes, and autoimmune hemolysis

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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.