CLINICAL TRIALS AND OBSERVATIONS Idiopathic CD4 lymphocytopenia: natural history and prognostic factors

a rare non–HIV-related syndrome with un-clear natural history and prognosis. This prospective natural history cohort study describes the clinical course, CD4 T lym-phocyte kinetics, outcome, and prognos-tic factors of ICL. Thirty-nine patients (17 men, 22 women) 25 to 85 years old with ICL were evaluated between 1992 and 2006, and 36 were followed for a median of 49.5 months. Cryptococcal and nontuberculous mycobacterial infections were the major presenting opportunistic infections. Seven patients presented with no infection. In 32, CD4 T-cell counts remained less than 300/mm3 throughout the study period and in 7 normalized after an average of 31 months. Overall, 15 (41.6%) developed an opportunistic infec-tion in follow-up, 5 (13.8%) of which were “AIDS-defining clinical conditions, ” and 4 (11.1%) developed autoimmune diseases. Seven patients died, 4 from ICL-related opportunistic infections, within 42 months after diagnosis. Immunologic analyses revealed increased activation and turn-over in CD4 but not CD8 T lymphocytes. CD8 T lymphocytopenia (< 180/mm3) and the degree of CD4 T cell activation (mea-sured by HLA-DR expression) at presenta-tion were associated with adverse out-come (opportunistic infection-related death; P .003 and.02, respectively). This trial is registered a