Autoantibodies to Erythrocytes
Erythrocyte autoantibodies may be benign, present in the plasma of healthy individuals, or pathologic, causing autoimmune hemolysis. Autoimmune hemolytic anemia (AIHA) consists of two major clinical disorders: cold hemagglutinin disease (cold AIHA), due to an IgM antibody that preferentially agglutinates red blood cells (RBC) in the cold (4 °24°C), and the more common syndrome of warm reactive (37°C) IgG-induced autoimmune hemolytic anemia (warm AIHA). In cold AIHA, the IgM autoantibody induces clearance of red blood cells (RBC) in the liver through complement activation and deposition of C3 on erythrocytes (9). This complement-dependent hepatic clearance responds poorly to corticosteroids and splenectomy. In warm AIHA, the IgG-coated erythrocytes are cleared primarily via Fc receptors on reticuloendothelial cells in the spleen. This process usually responds to corticosteroids and splenectomy (Table 1). These autoimmune hemolytic disorders may be idiopathic or develop as a complication of a lymphoproliferative disorder, infection, or drug therapy. The diversity of RBC autoantibodies occurring in these different clinical settings has not yet been completely defined. In contrast, the diversity of autoantibodies involved in the pathogenesis of other autoimmune diseases, such as systemic lupus erythematosus and myasthenia gravis, has been explored in various ways by different laboratories (5, 10). From these studies it appears that distinctive clones of autoantibody-producing cells are associated with particular disease processes. Similar restrictions in antibody clonality may also be present in immune-mediated hemolytic disease. To date, the complexity of erythrocyte autoantibody expression has been approached by examination of the antigen-binding properties (specificities) of these immunoglobulins and by analysis of their heavy and light chain isotypes. The following will review the current knowledge of the specificity (function), isotype, and cellular origin of these antibodies.