INTRATHECAL IGG SYNTHESIS AND ALBUMIN LEAKAGE ARE INCREASED IN SUBJECTS WITH HIV-1 NEUROLOGIC DISEASE

We analyzed matched cerebrospinal fluid and blood samples from 139 sub jects enrolled in a study of the effects of human immunodeficiency vir us type 1 (HIV-1) on the nervous system. Mean total intrathecal IgG sy nthesis rate was significantly higher in subjects with HIV-1-related n eurologic disease (NeuroPos) than in HIV-1-seropositive (HIV +) subjec ts without neurologic disease (NeuroNeg) or at-risk seronegative contr ols (SNC). Mean trans-blood-brain barrier (BBB) albumin leakage (AL) r ate increased significantly across groups (SNC < NeuroNeg < NeuroPos). AL was significantly higher in subjects with absolute CD4 counts <100 /mm(3) versus those with greater than or equal to 100 cells/mm(3) and significantly higher in AIDS compared with asymptomatic HIV +. Elevate d total intrathecal IgG synthesis rate could not be accounted for sole ly by the presence of a damaged BBB, because 79% of subjects with elev ated IgG synthesis rates had a normal BBB as assessed by the AL formul a. Furthermore, the Tourtellotte formula inherently corrects for BBB l eakage. We confirmed, using state-of-the-art albumin and IgG determina tions, that intrathecal IgG synthesis is prevalent in all stages of HI V-1 disease. In the absence of a CNS opportunistic infection or tumor, mean total intrathecal IgG synthesis rate and trans-BBB AL are signif icantly higher in subjects with clinical HIV-1 CNS disease than in neu rologically normally HIV + subjects.