Levels of the circulating cell adhesion molecule E-selectin and disease progression in HIV infection

Abstract

The levels of soluble form of E-Selectin (sEs), or endothelial-leukocyte adhesion molecule-1, were measured in 96 sera derived from 72 HIV-infected patients at different stages of the disease, 60 healthy blood donors, and 50 HIV-negative patients with infections, using a quantitative ELISA. Levels of sEs in HIV-infected individuals without AIDS, according to the 1993 classification system of the Centers for Disease Control, were higher than normal (mean +/- SEM 48 +/- 4 versus 35 +/- 3 ng/ml, p = 0.003). Patients with established AIDS, who were afebrile and had no evidence of acute concurrent infection, had even higher sEs serum levels (70 +/- 9 ng/ml, p = 0.009, compared to those without AIDS). A significant increase in clinical category disease progression was present. Individual concentrations of sEs correlated directly with levels of soluble intercellular adhesion molecule-1 (p < 0.00001) and IL-2 receptor (p = 0.001), but not with CD4+ T-cell counts. Zidovudine treatment was not associated with changes in sEs serum levels. Elevated sEs levels were also found in HIV-seronegative patients with other bacterial and protozoal infections. Since sEs is a biologically active molecule, further studies should investigate the pathogenetic significance of circulating sEs in HIV-related disease progression, and assess the prognostic value of sEs determination for these patients.

Levels of Soluble CD40 Ligand (CD154) in Serum Are Increased in Human Immunodeficiency Virus Type 1-Infected Patients and Correlate with CD4+T-Cell Counts

“…Although the immunological correlates of the elevated serum sCD40L levels associated with HIV-1 infection will require further study, we conclude that this molecule, unlike other non-T-cell-specific soluble molecules, which reflect panimmune system activation (15,16), could serve as an additional surrogate marker for the assessment of treatment efficacy. Such measurements could be useful in settings where wellequipped laboratories and funding required for CD4 ϩ T-cell and viral-load measurements are not available.…”

Expanding Role of Circulating Adhesion Molecules in Assessing Prognosis and Treatment Response in Human Immunodeficiency Virus Infection

“…sEs is biologically active; it can inhibit leukocyte adhesion (29) and activate polymorphonuclear cells via the CD11b integrin receptor (44). As we have shown, levels of sEs in HIV-infected patients (without concomitant fever, opportunistic infection, or neoplasm) are elevated compared to those in healthy controls, while a significant increase was observed with disease progression (75). Although some subsequent studies confirmed the elevated levels of sEs compared to those for healthy controls (52,73), in other studies no significant differences were demonstrated (3,28,45) (Table 2).…”

“…Individual serum sEs levels correlated strongly with levels of sICAM-1 and IL-2 receptor in serum but not with CD4 ϩ T-cell counts (75). Subsequent studies reported a marginal correlation or no correlation of sEs with CD4 ϩ T-cell counts (45,52).…”

“…Studies performed prior to the advent of HAART showed that antiretroviral treatment with zidovudine had no effect on the elevated levels of sICAM-1 or sEs (75,77). In contrast, a study of pediatric patients showed a statistically significant reduction in sICAM-1 levels in HIV-infected children undergoing therapy with zidovudine (54).…”

Albuminuria Is Associated with Elevated Acute Phase Reactants and Proinflammatory Markers in HIV-Infected Patients Receiving Suppressive Combination Antiretroviral Therapy

“…39 Other studies showed higher VCAM-1 and E-selectin levels in adult HIV patients with and without treatment, 40,41 and they were a potential marker of disease progression and death. 42,43 Recently, VCAM-1 was found to be associated with greater carotid intima media thickness in another study from our group. 44 Our current study is the first study showing the association of VCAM-1 and Eselectin with albuminuria in HIV-infected patients.…”