Monocyte CD49e and 110-120 kDa fibronectin fragments: HIV prognostic indicators independent of viral load and CD4 T-cell counts

OBJECTIVE:: To investigate the prognostic impact of chronic inflammation associated with HIV infections. Previously, we had observed that proteases, released in the course of HIV infections, cause 110-120 kDa fibronectin fragments (FNf) to appear in the blood of many patients. In vitro, at concentrations within the range found in patients plasma, FNf stimulate monocytes to release proteolytic enzymes that remove CD49e from the cell surface and produce cytokines that suppress proliferation of activated T cells when stimulated by agents that crosslink their antigen receptors. DESIGN:: A long-term observational study of patients whose plasma FNf and monocyte CD49e had been measured at 90-day intervals for 1.4 ± 0.5 years. METHODS:: Plasma FNf was measured by a quantitative western blot assay and monocyte CD49e expression by flow cytometry. Patients were monitored clinically for up to 5 years after enrollment. RESULTS:: All-cause mortality was significantly higher in patients who had at least 5 μg/ml FNf in more than 50% of plasma samples and/or persistent depletion of monocyte CD49e. Persistence of FNf and depletion of monocyte CD49e were not associated with changes in viral load or CD4 T-cell counts. ONCLUSION:: Persistently reduced expression of blood monocyte CD49e and/or the persistent presence of FNf in plasma are adverse prognostic markers in HIV-infected patients.