Search

Background: Patients with autoimmune lymphoproliferative syndrome (ALPS) have an autosomal dominant genetic defect that affects lymphocyte apoptosis and is associated with chronic nonmalignant lymphadenopathy, splenomegaly, and autoimmunity, particularly affecting RBCs, WBCs, and platelets., Study Design and Methods: DATs were performed on 34 consecutive patients with ALPS and 37 of their clinically unaffected relatives. The effects of age, sex, race, and immunoglobulin levels on the incidence of autoantibodies and clinical hemolysis were assessed., Results: The DAT was positive in 21 (62%) of ALPS patients but in only 1 (3%) of their relatives (p = 0.001). The DAT reacted because of IgG alone in 43 percent, complement alone in 5 percent, and IgG plus complement in 19 percent; 33 percent of the patients' cells had a positive reaction with polyspecific reagent only. All 10 ALPS patients with a history of hemolytic anemia had a positive DAT. Sixty percent of them had only IgG on their cells, 30 percent had IgG and complement, and 10 percent reacted only with polyspecific reagent. Of the 11 patients with a positive DAT and no history of hemolytic anemia, IgG alone was present in 27 percent, complement alone in 9%, and IgG plus complement in 9 percent; 55 percent had positive DATs only with polyspecific reagent. Among ALPS patients, those with a positive DAT had greater quantities of cells with increased alpha and ss T-cell receptors that phenotyped as CD4-CD8- and higher IgG levels., Conclusions: The DAT results in ALPS patients are most similar to those found in warm autoimmune hemolytic anemia. The DAT is useful to distinguish affected and unaffected persons within an ALPS family.

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.