title: Intrathecal IgG synthesis and albumin leakage are increased in subjects with HIV-1 neurologic disease.
abstract: We analyzed matched cerebrospinal fluid and blood samples from 139 subjects enrolled in a study of the effects of human immunodeficiency virus type 1 (HIV-1) on the nervous system. Mean total intrathecal IgG synthesis rate was significantly higher in subjects with HIV-1-related neurologic disease (NeuroPos) than in HIV-1-seropositive (HIV+) subjects without neurologic disease (NeuroNeg) or at-risk seronegative controls (SNC). Mean trans-blood-brain barrier (BBB) albumin leakage (AL) rate increased significantly across groups (SNC < NeuroNeg < NeuroPos). AL was significantly higher in subjects with absolute CD4 counts < 100/mm3 versus those with > or = 100 cells/mm3 and significantly higher in AIDS compared with asymptomatic HIV+. Elevated total intrathecal IgG synthesis rate could not be accounted for solely by the presence of a damaged BBB, because 79% of subjects with elevated IgG synthesis rates had a normal BBB as assessed by the AL formula. Furthermore, the Tourtellotte formula inherently corrects for BBB leakage. We confirmed, using state-of-the-art albumin and IgG determinations, that intrathecal IgG synthesis is prevalent in all stages of HIV-1 disease. In the absence of a CNS opportunistic infection or tumor, mean total intrathecal IgG synthesis rate and trans-BBB AL are significantly higher in subjects with clinical HIV-1 CNS disease than in neurologically normally HIV+ subjects.
authors.affiliation: Neurology and Research Services, VAMC West Los Angeles 90073.
authors.forename: E J
authors.initials: EJ
authors.lastname: Singer
authors.forename: K
authors.initials: K
authors.lastname: Syndulko
authors.forename: B
authors.initials: B
authors.lastname: Fahy-Chandon
authors.forename: P
authors.initials: P
authors.lastname: Schmid
authors.forename: A
authors.initials: A
authors.lastname: Conrad
authors.forename: W W
authors.initials: WW
authors.lastname: Tourtellotte
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000134:cerebrospinal fluid / Q000378:metabolism*; D001812:Blood-Brain Barrier; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid*; D006679:HIV Seropositivity / Q000097:blood / Q000134:cerebrospinal fluid; D015497:HIV-1; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry; D009422:Nervous System Diseases / Q000097:blood / Q000134:cerebrospinal fluid*; D012709:Serum Albumin / Q000032:analysis
chemical_list: D000418:Albumins; D007074:Immunoglobulin G; D012709:Serum Albumin