T-cell Apoptosis in Children with Autoimmune Lymphoproliferative Syndrome (ALPS)/Canale-Smith Syndrome (CSS)

Abstract

Mutations in the CD95 receptor (R) gene, a key regulator of programmed cell death (apoptosis) in lymphocytes, have been identified in patients suffering from autoimmune lymphoproliferative syndrome (ALPS) or Canale-Smith syndrome (CSS). ALPS/CSS is characterized by chronic non-malignant lymphadenopathy, hepatosplenomegaly, and autoimmune cytopenias. Twenty patients with symptoms of ALPS/CSS were screened for defects in T cell apoptosis. Specific anti-CD95-induced cell death of in vitro activated T cells was lower in ALPS/CSS patients compared to 12 healthy controls (CD4: 28 ′ 5 vs. 79 ′ 5%; CD8: 30 ′ 4 vs. 85 ′ 5%; mean ′ SEM, p < 0.001) while spontaneous cell death was slightly increased (CD4: 28 ′ 4 vs.14 ′ 1%, p < 0.01; CD8: 30 ′ 4 vs. 22 ′ 2%, p < 0.09). Specific anti-CD3 (i.e., activation)-induced cell death (AICD) was also lower in ALPS/CSS patients than in healthy controls (CD4: 1 ′ 3 vs. 20 ′ 3%; CD8: 4 ′ 3 vs. 27 ′ 3%, p < 0.001). Analysis of sequence-specific DNA conformation polymorphisms (SSCP) had a low sensitivity for detection of new mutations in the CD95-R gene since false-negative SSCP-results were obtained in 5 out of 7 patients with known CD95-R mutations.