Expansion of monocyte subset could serve as a biomarker for HIV progressions

Mar 31 2008

An increase in the CD163+/CD16+ monocyte subset could be a biomarker for the progression of HIV disease, according to researchers at Temple University.

The researchers reported their findings, “CD163/CD16 Coexpression by Circulating Monocytes/Macrophages in HIV: Potential Biomarkers for HIV Infection and AIDS Progression,” in the March issue of AIDS Research and Human Retroviruses (www.liebertonline.com/aid).

A monocyte is a specific white blood cell, a part of the human body's immune system that protects against blood-borne pathogens and moves quickly to sites of infection within the body's tissues. As monocytes enter tissue, they undergo a series of changes to become macrophages.

The researchers were investigating alterations in this monocyte subset in patients with HIV infection. As part of this study, they examined a cohort of 18 patients from the Comprehensive HIV Program at Temple University Hospital, under the direction of Ellen Tedaldi, and seven individuals without HIV infection.

“At first, we were just looking at whether or not we saw alterations in this CD163+/CD16+ subset and whether it might be reflective of the amount of virus they have in circulation,” said Tracy Fischer-Smith, an associate scientist in Temple's Neuroscience Department and the study's lead author. “We did, indeed, find that patients with detectable virus had an increase of this monocyte subset that correlated with the amount of virus they had in their blood. We were surprised to find that patients with CD4+ T cell counts of less than 450 cells per microliter [200 or less per microliter is defined as AIDS], the increase of this monocyte subset correlates inversely with the number of T cells.”

Fischer-Smith said this finding suggests that as the monocyte cells are increasing, these patients are losing CD4+ T cells, which are critical for the maintenance of immunological competence.

“This may actually provide an earlier window into what is happening with HIV-infected patients where we might be able to see that immune impairment is taking place before we see a dramatic loss of CD4+ T cells,” she said.

“It looks like, based on these correlations, that this particular cell type may be involved in immune impairment and the progression of HIV,” said Jay Rappaport, professor of neuroscience and neurovirology, who oversaw the study. “Is it a good prognostic indicator" If you have a lot of these monocytes, does it mean you are going to progress into AIDS faster" “Right now, all we know is what the correlations are,” he said.

Rappaport added that he believes the CD163+/CD16+ monocyte subset is the first biomarker that correlates with viral load and CD4+ count. “The fact that it actually correlates with both, we think, might make it a key cell type in the pathogenesis of AIDS.” Fischer-Smith said the researchers plan to expand this study by following a cohort of patients longitudinally to see if their findings really can provide doctors with an early warning system and help to design better therapeutic strategies.

“When you are just looking at a single time-point, you don't know how changes in this monocyte subset might occur over time, and how these changes might relate to the viral load and T cell number in individual patients,” she said. “That is why we want to investigate this further with a longitudinal study of HIV patients.”