Autoimmune lymphoproliferative syndrome in a patient with common variable immunodeficiency: dichotomy of apoptosis

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder usually associated with hypergammaglobulinemia and defective apoptosis mostly due to Fas or Fas ligand mutation. Common variable immunodeficiency (CVID) is a disorder with hypogammaglobulinemia commonly associated with increased Fas expression and spontaneous apoptosis.

To describe a patient with a unique combination of hypogammaglobulinemia and ALPS with Fas deficiency but high spontaneous apoptosis.

Fas expression on freshly isolated lymphocytes was evaluated by means of immunofluorescence using polyclonal rabbit anti-Fas IgG antibody. Apoptosis of cultured lymphocytes was quantitated using acridine orange and ethidium bromide staining.

We describe a male patient diagnosed as having CVID at the age of 10 years receiving monthly intravenous immunoglobulin. The patient developed ALPS at the age of 21 years manifested by persistent lymphadenopathy and hepatosplenomegaly. The percentage of double-negative T lymphocytes was estimated to be 9%. Freshly isolated lymphocytes showed low Fas expression (3.6% for the patient and 11.2% for the control). The spontaneous apoptosis rate was high (15% for the patient and 5% for the control).

Autoimmune lymphoproliferative syndrome can be associated with hypogammaglobulinemia and should be looked for in chronic nonmalignant lymphoproliferation in CVID. Common variable immunodeficiency might involve Fas-independent pathways or recruitment of Fas downstream molecules for apoptosis. There is a subset of patients with both CVID and ALPS in whom Fas deficiency could be associated with enhanced spontaneous apoptosis.