Background: Autoimmune lymphoproliferative syndrome (ALPS) is a recently recognized and rare disorder associated with inherited defects in the FAS: gene or other regulators of lymphocyte apoptosis. It is characterized by massive lymphadenopathy; splenomegaly; autoimmunity including episodes of immune hemolytic anemia, thrombocytopenia, and neutropenia.(1) The serologic basis for immune cytopenias associated with ALPS has not been previously characterized.

Study design and methods: RBC, granulocyte, and platelet serologies for ALPS patients and hepatitis C patients were assessed. Medical records were reviewed for clinical, immunologic, serologic, and transfusion history. Testing included: DAT; serum screening for antibodies to RBCs, granulocytes, platelets, cardiolipin, penicillin-coated RBCs, and human leukocyte antigens; antibody identification and IgG subclass; RBC phenotype.

Results: In a cohort of 11 patients with apoptosis defects (eight with heterozygous FAS: gene mutations); many had histories of hemolytic anemia (7), thrombocytopenia (4), and/or leukopenia (11); nine received steroid therapy, seven underwent splenectomy; five had been remotely transfused. On the basis of serologic testing even when they were clinically stable, nine had positive DATs; two had alloantibodies; 6 had IgG and/or IgM antibodies to cardiolipin; seven had platelet-directed antibodies; three had granulocyte-directed antibodies; none had HLA antibodies.

Conclusions: Nearly all ALPS patients have antibodies directed against one or more hematopoietic cell lineages. Serologic testing is critical in the evaluation of these individuals and when transfusion is indicated, red cells that are matched for clinically significant C, E, and K antigens should be considered.