It is unlikely that sequestration in an enlarged spleen and/or in other lymphoid tissue in the reticuloendothelial system may entirely explain the development of CD4 lymphopenia in ALPS-FAS as hypersplenism and lymphadenopathy are present in the majority of patients, while CD4 lymphopenia is observed only in a small subset. This evidence concerns the gene CD4 and autoimmune lymphoproliferative syndrome.