Expanding mechanistic insights into the pathogenesis of idiopathic [CD4.sup.+] T cell lymphocytopenia

Idiopathic [CD4.sup.+] T cell lymphocytopenia (ICL) is a heterogeneous syndrome presenting with persistent [CD4.sup.+] T cell lymphopenia of unknown origin, and opportunistic infections in some patients. The underlying pathogenesis and appropriate management remain understudied. In this issue of the JCI, Perez-Diez and Wong et al. assessed the prevalence of autoantibodies from the sera of 51 adult ICL patients (out of a cohort of 72). Some patients showed high levels of IgG and IgM autoantibodies against numerous autoantigens, and some autoantibodies were specific for lymphocytes. The researchers implicate these autoantibodies as a possible pathogenic mechanism responsible for the reduction in circulating [CD4.sup.+] T cells. This study goes beyond defining a mechanism in a complex, poorly defined disease; it also brings a renewed focus on ICL that will likely result in improved diagnostic evaluation and treatment.