Purpose: Immunodeficiency is one of the key features of 22q11.2 deletion syndrome (del), and it is seen in approximately 75% of the patients. The degree of immunodeficiency varies widely, from no circulating T cells to normal T cell counts. It has been hypothesized that the low number of T cells may at least in part be due to increased apoptosis of T cells. Increased spontaneous T cell apoptosis has been reported in one patient with 22q11.2del, but this has not been further investigated.
Methods: A national cohort of patients with a proven heterozygous deletion of chromosome 22q11.2 diagnosed by FISH or MLPA and a group of age and sex matched controls were studied. Spontaneous and activation-induced apoptosis, in addition to FAS expression on lymphocytes, were measured using flow cytometry. Serum levels of FASL were analyzed using ELISA.
Results: There was no increased spontaneous apoptosis in patients with 22q11.2del. Upon activation, anti-FAS-induced apoptosis was significantly increased in patients compared to those in controls, while there was no difference in activation induced cell death or activated cell autonomous death. We also found a significant increase in expression of FAS on freshly isolated lymphocytes from patients, while there was no difference in serum levels of FASL. Patients with congenital heart defects (CHD) had significantly higher serum levels of FASL compared to non-CHD patients.
Conclusion: We have shown increased FAS expression on lymphocytes from patients with 22q11.2del as well as increased levels of FASL in patients with CHD. Those changes may contribute to the pathophysiology of the 22q11.2del.
Keywords: 22q11.2 deletion syndrome; 22q11.2del; FAS; FAS-L; apoptosis; primary immunodeficiencie.