Autoimmune lymphoproliferative syndrome (ALPS) is a disorder associated with heritable defects in lymphocyte apoptosis that result in chronic nonmalignant lymphadenopathy, splenomegaly, and autoimmunity. To examine the prevalence, mechanisms, and potential implications of eosinophilia in ALPS, we reviewed data retrospectively from 187 consecutive ALPS patients and their family members studied at the National Institutes of Health. ALPS patients with eosinophilia were compared with ALPS patients without eosinophilia with respect to their clinical and immunologic phenotype. Potential mechanisms for the eosinophilia, including abnormal Fas-mediated eosinophil apoptosis, increased production of eosinophilopoietic cytokines, and presence of anti-eosinophilic autoantibodies were also explored in a small number of patients from whom samples were available. Analysis of data from 68 ALPS patients and 119 of their relatives identified a distinct subgroup of patients with prominent and persisting eosinophilia that proved to be associated with increased numbers of peripheral blood leukocytes (PBL) of multiple lineages and a trend towards increased serum IgE levels. Eosinophilic ALPS patients also had a significantly higher risk of death due to infectious complications. Although the specific etiology of the eosinophilia in these patients remains uncertain, it does not appear to be associated with an altered serum cytokine profile, increased survival responsiveness of eosinophils to IL-5, defective Fas-mediated eosinophil apoptosis, or anti-eosinophil antibodies. Eosinophilia defines a distinct subgroup of ALPS patients with increased serum IgE levels, increased numbers of PBL of multiple lineages, and higher mortality from infectious complications.
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