Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors

Blood. 2008 Jul 15;112(2):287-94. doi: 10.1182/blood-2007-12-127878. Epub 2008 May 2.


Idiopathic CD4(+) lymphocytopenia (ICL) is a rare non-HIV-related syndrome with unclear natural history and prognosis. This prospective natural history cohort study describes the clinical course, CD4 T lymphocyte kinetics, outcome, and prognostic 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/mm(3) throughout the study period and in 7 normalized after an average of 31 months. Overall, 15 (41.6%) developed an opportunistic infection 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 turnover in CD4 but not CD8 T lymphocytes. CD8 T lymphocytopenia (< 180/mm(3)) and the degree of CD4 T cell activation (measured by HLA-DR expression) at presentation were associated with adverse outcome (opportunistic infection-related death; P = .003 and .02, respectively).

Trial registration: NCT00001319.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoimmune Diseases
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphocyte Activation
  • Lymphopenia / complications
  • Lymphopenia / diagnosis
  • Lymphopenia / epidemiology*
  • Lymphopenia / microbiology
  • Male
  • Middle Aged
  • Opportunistic Infections
  • Prognosis
  • Prospective Studies
  • Survival Analysis
  • T-Lymphocytes

Associated data