In this paper we reported the association between a rare disease, the IgG4-related disease, and the idiopathic CD4 lymphocytopenia (ICL), a heterogenic and rare syndrome of unknown etiology characterized by the detection of a persistent absolute CD4 T cells count <300 cells/mm3 (or <20% of total T cells) in more than one occasion and no evidence of HIV infection in absence of immunodeficiency or therapy associated with depressed levels of CD4 T cells [11]. This evidence concerns the gene CD4 and immunodeficiency disease.