Seroreactivity to Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) latent nuclear antigen in AIDS-associated Kaposi's sarcoma patients depends on CD4+ T-cell count

In AIDS/Kaposi's sarcoma (KS) patients, the sensitivity of immunofluorescence assays for detecting antibodies against latent nuclear antigen ranges from 52% to 93%. However, in classic and African KS, sensitivities above 90% have been reported systematically. This study evaluates whether CD4+ T-cell count affects seroreactivity to KSHV LANA and to lytic antigens in AIDS/KS patients. Kaposi's sarcoma-associated herpesvirus (KSHV) latent (IFA-LANA) and lytic (IFA-Lytic and ORF65/K8.1 EIA) antibodies were screened in 184 consecutive samples taken from 36 AIDS/KS patients grouped according to their CD4+ counts as follows: < 100 (group A), 100-300 (group B), and > 300 (group C) cells/ mm(3). At enrollment, the immunofluorescence assay for the detection of antibodies against latent nuclear antigen (IFA-LANA) was positive in 3/11(27.2%) group A patients, in 10/11 (90.9%) group B patients, and in 14/14 (100%) group C patients (P < 0.01). Seropositivity to lytic antigens did not differ according to CD4+ T-cell count. Considering IFA-Lytic and ORF65/K8.1 EIA, seropositivity for lytic antigens was 100% in all three patient groups. In patients whose CD4+ count improved during follow-up, IFALANA seroconversion occurred; unstable counts resulted in a decrease in LANA antibody titers while the persistence of high counts resulted in unchanged, elevated antibody titers. In conclusion, LANA seroreactivity in AIDS/KS patients, as assessed by an immunofluorescence assay, depends on CD4+ T-cell count, rendering this evaluation important in the interpretation of seroepiderniological studies of KSHV infection in AIDS patients. To evaluate future serological tests based on latency-associated antigens, the selection of sera from KS patients with CD4+ cell count > 300 cells/mm(3) as a positive gold standard is recommended.