Blood, 15 May 2002, Vol. 99, No. 10, pp. 3491-3491
CD47 and the control of immune hemolysis
Oldenborg and colleagues (page 3500) provide convincing
evidence for the role of CD47 in modulating immune hemolysis in NOD mice, which are naturally prone to the development of mild
autoimmune hemolysis. Previously, these investigators have shown that
CD47-SIRP
signaling inhibits macrophage activation and
phagocytosis of opsonized red blood cells (RBCs). Interestingly,
CD47
/ NOD mice develop lethal autoimmune hemolysis,
which is attributed in part to markedly increased clearance of
CD47-deficient RBCs and higher levels of surface-bound RBC
autoantibodies. Importantly, the NOD genetic background is a
prerequisite for autoimmune hemolysis since lethal hemolysis was
not observed in CD47/ nonautoimmune-prone mice, for
example, the C57BL6 mice. Thus, CD47-mediated signaling, or the lack
thereof, does not initiate but rather influences the severity and
progression of autoimmune hemolysis. Which factors contribute to the
severity of hemolysis in patients with autoimmune hemolytic anemia has
been much debated. Many previous studies have focused on quantitative
and qualitative aspects of RBC autoantibodies. For example, the IgG
isotype of the RBC autoantibody correlates with macrophage clearance.
But IgG RBC autoantibodies of various "pathogenic" isotypes also
can be found in individuals without immune hemolysis. Similarly, the quantity or specificity of the RBC autoantibody by themselves does not
predict severity and course of hemolysis in patients. More recently,
IgG Fc receptors with inhibitory functions, reminiscent of the SIRP
receptor, have attracted much interest. These types of receptors likely
play a significant role in controlling both the generation of RBC
autoantibodies, as well as the rate of RBC clearance. Advances in the
therapy of autoimmune hemolytic anemia, currently limited for the
most part to corticosteroids, splenectomy, and transfusion, are
needed. It will be exciting to see whether targeting the CD47/SIRP
receptor pair will prove to be a feasible approach for attenuating
pathologic RBC autoimmune responses and their sequelae.
Leslie Silberstein
Harvard University
