Patients with autoimmune lymphoproliferative syndrome (ALPS) have an autosomal dominant genetic defect that affects lymphocyte apoptosis associated with chronic non-malignant lymphadenopathy, splenomegaly and autoimmunity particularly affecting blood cells. Direct antiglobulin tests (DAT) were performed on 34 consecutive patients with ALPS and 37 of their clinically unaffected relatives. The effects of age, gender, race, and immunoglobulin levels on the incidence of autoantibodies and clinical hemolysis were assessed. The DAT was positive in 21 (62 percent) of ALPS patients but only in one (3 percent) of their relatives (p=0.001). The DAT was reactive due to IgG alone in 43 percent, complement alone in 5 percent, IgG plus complement in 19 percent, and 33 percent of the patients? cells had a positive reaction with polyspecific reagent only. All ten ALPS patients with a history of hemolytic anemia had a positive DAT. Sixty-percent of patients had only IgG on their cells, 30 percent had IgG and complement, and 10 percent of patients with a history of hemolytic anemia 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 percent, IgG plus complement accounted for 9 percent, and 55 percent had positive DATs only with polyspecific reagent. Among ALPS patients, those with a positive DAT had greater quantities of TCR a/b+ CD4-CD8- cells and higher IgG levels. 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 individuals within an ALPS family. Preliminary studies have found that the incidence of ALPS patients with neutrophil and platelet specific antibodies is much lower than the incidence of RBC antibodies.
