6533b7dcfe1ef96bd1272007
RESEARCH PRODUCT
Missense mutations in the fas gene resulting in autoimmune lymphoproliferative syndrome: A molecular and immunological analysis
L D NotarangeloE Quiròs-roldanAlessandra BettinardiA CorreraDuilio BrugnoniS. La GruttaA Malagolisubject
Antigens Differentiation T-LymphocyteMaleAdolescentT-LymphocytesCD3ImmunologyLymphoproliferative disordersBiologyLymphocyte ActivationAutoimmune DiseaseBiochemistryFas ligandImmunophenotypingImmune systemPedigree; Antigens Differentiation T-Lymphocyte; Solubility; Apoptosis; Autoimmune Diseases; Humans; Antigens CD95; Child; Lymphocytes; Child Preschool; Lymphocyte Activation; Syndrome; Lymphoproliferative Disorders; Adolescent; Mutation; Immunophenotyping; Male; Biological Markers; T-LymphocytesmedicineChildAutoimmune diseaseApoptosiSyndromeCell BiologyHematologymedicine.diseaseFas receptorPedigreeAntigens CD95SolubilityApoptosisChild PreschoolLymphoproliferative DisorderAutoimmune lymphoproliferative syndromeMutationBiological MarkerImmunologybiology.proteinLymphocyteHumandescription
AbstractProgrammed cell death (or apoptosis) is a physiological process essential to the normal development and homeostatic maintenance of the immune system. The Fas/Apo-1 receptor plays a crucial role in the regulation of apoptosis, as demonstrated by lymphoproliferation in MRL-lpr/lpr mice and by the recently described autoimmune lymphoproliferative syndrome (ALPS) in humans, both of which are due to mutations in the Fas gene. We describe a novel family with ALPS in which three affected siblings carry two distinct missense mutations on both the Fas gene alleles and show lack of Fas-induced apoptosis. The children share common clinical features including splenomegaly and lymphadenopathy, but only one developed severe autoimmune manifestations. In all three siblings, we demonstrated the presence of anergic CD3+CD4−CD8− (double negative, [DN]) T cells; moreover, a chronic lymphocyte activation was found, as demonstrated by the presence of high levels of HLA-DR expression on peripheral CD3+ cells and by the presence of high levels of serum activation markers such as soluble interleukin-2 receptor (sIL-2R) and soluble CD30 (sCD30).
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1997-02-01 |