Severe autoimmune hemolytic anemia caused by a warm IgA autoantibody directed against the third loop of band 3 (RBC anion-exchange protein 1)

BACKGROUND: Autoimmune hemolytic anemia associated with only IgA autoantibodies reacting optimally at 37degreesC (WAIHA) is exceedingly rare. When identified, warm IgA autoantibodies specificities are usually directed to antigens of the Rh system. However, like IgG autoantibodies, the specificity of the majority of these antibodies is not identified. CASE REPORT: A case of a 3-year-old boy in whom a life-threatening IgA WAIHA occurred suddenly is reported. Following initial RBC transfusions and treatment with steroids at a dose of 3 mg per kg, which was slowly tapered, stabilization to a state of compensated hemolysis was achieved, persisting 4 months before complete resolution. There was no recurrence within a 16-month follow-up. STUDY DESIGN AND METHODS: The standard DAT in a gel column method with anti-IgG and anticomplement reagents was negative. However, the same method with an anti-IgA was strongly positive. RESULTS: The serum and the eluate obtained after acid elution reacted with all normal RBCs tested. Enzymatic treatment of panel RBCs by (x-chymotrypsin and pronase abolished the reactivity. The reaction was completely inhibited by RBC incubation with four different MoAbs directed against the third extracellular loop of band 3, the RBC anion-exchange protein 1 (AE1), whereas MoAbs against other specificities showed no effect. CONCLUSIONS: This is the first report of an IgA autoantibody directed against the band 3 (AE1) protein and, more specifically, against the third loop. Moreover, this case underlines the importance of including IgA research in the initial diagnostic evaluation when a hemolytic anemia is suspected to be autoimmune and when IgG and complement are not detected on the patient's RBCs.