Detection of high nerve growth factor serum levels in AIDS-related and -unrelated Kaposi's sarcoma patients

Objective: Nerve growth factor (NGF) is an autocrine survival factor for memory B lymphocytes. As functional B-cell deregulation is present during HIV infection, NGF serum levels were measured in HIV-infected patients and compared with the patients' clinical features. Design: Sera from 48 consecutive HIV-infected patients and matched healthy controls were retrospectively and blindly analysed. Sera fr-om seven patients with classical Kaposi's sarcoma (KS) were subsequently included in the study. The effects of NGF on spindle-shaped cells from KS lesions (KS cells) were also investigated. Methods: NGF titration was performed by enzyme-linked immunosorbent assay (ELISA) and human herpesvirus 8 (HHV-8) antibody testing by immunofluorescent assay (IFA). NGF receptors were assessed by Western blot analysis. Cell growth assays were performed by cell counting. Results: Very high median NGF serum revels were detected in all seven patients with AIDS-related KS (2500 pg/ml) compared with HIV-infected patients without KS (40 pg/ml), as well as in all seven classical KS patients (550 pg/ml) compared with healthy controls (20 pg/ml). In HIV-infected patients, NGF serum levels were significantly related to KS (P = 0.0038) by stepwise multiple regression analysis, and HHV-8 seropositivity was significantly associated with KS (P = 0.045) and to NGF levels (P = 0.001) by logistic regression analysis. KS cells did not produce NGF but expressed both NGF receptors and presented increased proliferation rate after exogenous NGF addition. Conclusions: These results strongly suggest that increased NGF levels, possibly related to HHV-8 infection, may be involved in KS progression. (C) 1998 Lippincott Williams & Wilkins.