Elevated serum level of Fas ligand correlates with the asymptomatic stage of human immunodeficiency virus infection.

To the Editor: human serum. For statistical analysis, serum samples that showed no detectable FasL were attributed a level of 30 pg/mL, equivalent to half of the lowest detectable concentration. The subjects tested Several reports have established an impotant role for Fas/Fas liwere 20 HIV-seronegative healthy controls, 28 asymptomatic HIVgand (FasL) interaction in mediating programmed cell death of CD4 seropositives (grade A according to the revised CDC classification), lymphocytes in human immunodeficiency virus (HIV)-infected suband 33 symptomatic/acquired immunodeficiency syndrome (AIDS) jects. Soluble forms of the Fas receptor and its ligand have also patients (18 with grade B and 15 with grade C). The asymptomatic been detected in supernatants of cultured cells or in human serum. patients had a mean CD4 count of 536/mL; none of them presented Elevated serum levels of soluble Fas were found to occur during with opportunistic infections and 11 of the 28 (39%) were receiving HIV infection; however, no correlation could be established between antiretroviral therapy. On the other hand, the symptomatic/AIDS serum Fas levels and stage of infection or progression to disease. patients had a mean CD4 count of 333/mL; only 4 of them (12%) Nevertheless, the enhanced release of soluble Fas was suggested to had associated opportunistic infections at the time serum samples be a host-defense mechanism against HIV infection and aberrant were taken and 79% were receiving antiretroviral drugs. Plasma apoptosis induction. On the other hand, soluble FasL was found to viral loads were available on samples from only 12 asymptomatics induce apoptosis in Fas-positive lymphocytes, and increased serum and 21 patients. No significant differences in viral loads (P ú .05; levels were reported in certain cancer patients and were associated Mann-Whitney U rank test) were detected among the 2 groups, with systemic tissue damage. In addition, HIV infection of CD4 although viral copies less than 2 1 10/mL were observed in 75% T cells and macrophages was found to upregulate FasL expression, of the asymptomatic patients and only in 48% of the symptomatic/ leading to enhanced lymphocyte apoptosis. Therefore, to gain further AIDS cases. insight into the role of FasL in the T-cell depletion during HIV The levels of soluble FasL in sera of all tested subjects are shown infection, we have analyzed serum levels of FasL from HIV-infected in Fig 1. Detectable levels were observed in sera of 30% of either subjects during the asyptomatic or the symptomatic/disease stage and healthy controls or symptomatic/AIDS patients and in 68% of HIVcompared the levels with those in sera of matched healthy controls. seropositive asymptomatics (P Å .0104 v controls and P Å .0035 v The quantification of serum FasL was performed using a sandwich patients; Fisher’s exact test). The mean { standard error of the mean enzyme-linked immunosorbent assay (ELISA) based on the use of of serum FasL levels (in picograms per milliliter) were 60 { 10 in 2 hamster monoclonal antibodies to FasL. The minimum detectable healthy subjects, 150 { 40 in patients (P ú .05; Mann-Whitney U level of FasL was reproducibly found to be 60 pg/mL using recombinant FasL protein as a standard diluted in normal (FasL-negative) rank test), and 410 { 120 in the asymptomatic patients (P Å .0025