Hemolytic anemia due to immune function is one of the major causes of
acquired hemolytic anemia. In recent years, as more is known about the immune system, these entities have become better understood and their treatment improved. In this section, we will discuss three areas in which this progress has been apparent. In Section I, Dr. Peter Hillmen outlines the recent findings in the pathogenesis of
paroxysmal nocturnal hemoglobinuria (PNH), relating the biochemical defect (the lack of
glycosylphosphatidylinositol [
GPI]-linked proteins on the cell surface) to the clinical manifestations, particularly
hemolysis (and its effects) and
thrombosis. He discusses the pathogenesis of the disorder in the face of marrow dysfunction insofar as it is known. His major emphasis is on
innovative therapies that are designed to decrease the effectiveness of complement activation, since the lack of cellular modulation of this system is the primary cause of the pathology of the disease. He recounts his considerable experience with a humanized
monoclonal antibody against C5, which has a remarkable effect in controlling the manifestations of the disease. Other means of controlling the action of
complement include replacing the missing modulatory
proteins on the cell surface; these studies are not as developed as the former agent. In Section II, Dr. Alan Schreiber describes the biochemistry, genetics, and function of the
Fc gamma receptors and their role in the pathobiology of
autoimmune hemolytic anemia and
idiopathic thrombocytopenic purpura due to
IgG antibodies. He outlines the complex varieties of these molecules, showing how they vary in genetic origin and in function. These variations can be related to three-dimensional topography, which is known in some detail. Liganding
IgG results in the transduction of a signal through the
tyrosine-based activation motif and Syk signaling. The role of these receptors in the pathogenesis of
hematological diseases due to
IgG antibodies is outlined and the potential of
therapy of these diseases by regulation of these receptors is discussed. In Section III, Dr. Wendell Rosse discusses the forms of
autoimmune hemolytic anemia characterized by
antibodies that react preferentially in the cold-
cold agglutinin disease and
paroxysmal cold hemoglobinuria (PCH). The former is due to
IgM antibodies with a common but particular structure that reacts primarily with
carbohydrate or
carbohydrate-containing
antigens, an interaction that is diminished at body temperature. PCH is a less common but probably underdiagnosed illness due to an
IgG antibody reacting with a
carbohydrate antigen; improved techniques for the diagnosis of PCH are described.
Therapy for the two disorders differs somewhat because of the differences in isotype of the antibody. Since the
hemolysis in both is primarily due to complement activation, the potential role of its control, as by the
monoclonal antibody described by Dr. Hillmen, is discussed.