Reappraisal of Idiopathic CD4 Lymphocytopenia at 30 Years

This original article presents an observational study of 91 patients with idiopathic CD4 lymphocytopenia (ICL) enrolled over 11 years, evaluating clinical presentation, genetics, immunologic profiles, and prognosis. ICL is defined as persistent CD4+ T-cell counts <300/mm³ without HIV or other known causes. Opportunistic infections (e.g., HPV-related disease, cryptococcosis) were common, and CD4 counts <100/mm³ conferred increased risk of infection and cancer, but lower risk of autoimmunity. Cancer prevalence was higher than in the general population, while mortality was similar. Some patients showed gradual T-cell recovery over time. Vaccine responses to SARS-CoV-2 were diminished in those with lower CD4 counts. Despite extensive sequencing, a genetic cause was found in only 7% of cases. The study concludes that ICL remains a distinct immunodeficiency with heterogeneous clinical manifestations requiring tailored surveillance and management.

This original article presents an observational study of 91 patients with idiopathic CD4 lymphocytopenia (ICL) enrolled over 11 years, evaluating clinical presentation, genetics, immunologic profiles, and prognosis. ICL is defined as persistent CD4+ T-cell counts <300/mm³ without HIV or other known causes. Opportunistic infections (e.g., HPV-related disease, cryptococcosis) were common, and CD4 counts <100/mm³ conferred increased risk of infection and cancer, but lower risk of autoimmunity. Cancer prevalence was higher than in the general population, while mortality was similar. Some patients showed gradual T-cell recovery over time. Vaccine responses to SARS-CoV-2 were diminished in those with lower CD4 counts. Despite extensive sequencing, a genetic cause was found in only 7% of cases. The study concludes that ICL remains a distinct immunodeficiency with heterogeneous clinical manifestations requiring tailored surveillance and management.