Elevated CD38 Antigen Expression on CD8+ T Cells Is a Stronger Marker for the Risk of Chronic HIV Disease Progression to AIDS and Death in the Multicenter AIDS Cohort Study Than CD4+ Cell Count, Soluble Immune Activation Markers, or Combinations of HLA-DR and CD38 Expression

Abstract

The prognostic value of several immunologic markers were compared in Los Angeles Multicenter AIDS Cohort Study (MACS) participants, most of whom had been infected with HIV for >8 years. Markers studied included CD4+ cell number, flow cytometric measurements of CD8+ cell expression of CD38 and HLA-DR antigens, and serum markers of immune activation including neopterin, beta2-microglobulin, soluble interleukin-2 receptor, soluble CD8, and soluble tumor necrosis factor receptor-alpha (TNF-alpha) type II. Cox proportional hazards models indicated that elevated CD38 on CD8, a flow cytometric measurement of CD8+ T-lymphocyte activation, was the most predictive marker of those studied for development of a clinical AIDS diagnosis and death. As compared with the reference group, who had CD38 on CD8 <2470 molecules per CD8+ cell and in whom 4 of 99 developed clinical AIDS within 3 years, participants with CD38 on CD8 between 2470 and 3899, 3900 and 7250, and >7250 had relative risks (and numbers developing AIDS within 3 years) of 5.0 (15 of 81), 12.3 (24 of 60), and 41.4 (36 of 49), respectively. The strong prognostic value of CD38 on CD8 measurements and the fundamental importance of chronic immune activation in the pathogenesis of HIV disease suggests that this marker might have utility in the clinical management of HIV-infected persons.

IL‐7Rα expression on CD4+ T lymphocytes decreases with HIV disease progression and inversely correlates with immune activation

“…Immune activation has been demonstrated to play a critical role in HIV disease progression [1][2][3][4][5][6][7][8][9][10][11][12][13][14], possibly through the induction of activation-induced cell death (AICD) of bystander non-infected cells [1,43]. We have also shown here that IL-7Ra expression inversely correlates with CD4 + T cell apoptosis, and that the level of apoptosis, particularly in the memory T cell subset, is significantly altered in groups with varied IL7Ra expression.…”

“…Although many correlates have been identified that may influence the rate of HIV progression, including immune activation, and the disruption of T cell homeostasis, a complete understanding of the mechanisms of CD4 + T cell decline remains elusive [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Cytokines that signal through the common gamma chain, such as IL-2, IL-4, IL-7, and IL-15, are some of the main mediators of T cell homeostasis [15][16][17][18][19][20][21].…”

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

“…Secondly, it must be stressed that CD38 transcription is a marker for other diseases. It is prognostic for HIV infected subjects [105], chronic lymphoid leukemia [106] and for diabetic patients with nephropathy [107]. Hence reduced CD38 transcription cannot be pathognomonic for ASD but nevertheless might prove of salient clinical value in a disorder diagnosed solely using behavioral assessments reliably carried out only at the age of three [104].…”

Relationship between CD38 expression on peripheral blood T‐cells and monocytes, and response to antiretroviral therapy: A one‐year longitudinal study of a cohort of chronically infected ART‐naive HIV‐1+ patients

“…progression independent of the plasma viral load and peripheral blood (PB) CD4þ T-cell counts (7)(8)(9)(10)(11)(12)(13). Furthermore, CD38 expression on CD8þ T-cells correlates with HIV-1 disease progression, and it also predicts further declines in PB CD4þ T-cells (11,14).…”