INTRATHECAL SYNTHESIS OF ANTIMYELIN BASIC-PROTEIN IGG IN HIV-1(+) PATIENTS

Human immunodeficiency virus type 1 (HIV-1)-infected individuals frequ ently develop a broad spectrum of neurological syndromes, classified a s HIV-1-associated cognitive/motor complex. Diffuse demyelination of h emispheric white matter is a commonly observed in HIV-1 infected brain , but the events leading to myelin destruction are still obscure. Sinc e oligodendrocyte infection by HIV-1 is not proven as yet, myelin dama ge in HIV-1 infection may result from indirect mechanisms such as the excessive release of myelinotoxic substances or the triggering of auto immune responses directed to myelin constituents. To verify the latter hypothesis, we searched for elevated anti-myelin basic protein (MBP) IgG levels in the cerebrospinal fluid (CSF) and serum of 25 patients w ith HIV-1 infection, 12 with multiple sclerosis (MS), and 9 with non-i nflammatory neurological diseases (NIND). CSF, but not serum, anti-MBP IgG levels were more frequently elevated in HIV-1(+) (16/25, 64%) tha n in MS (3/12, 25%) or NIND (0/9) patients. By using the anti-MBP IgG index, the anti-MBP IgG antibody specificity index (ASI), and the sear ch for anti-MBP oligoclonal IgG, we ascertained that anti-MBP IgG were produced within the CNS in 13 of 25 (52%) HIV-1(+), in 6 of 12 (50%) MS, and in none of NIND patients. The incidence of increased CSF anti- MBP IgG levels was higher among HIV-1(+) patients at stage II-III (4/4 , 100%) or at stage IV B (7/9, 78%) than among those at stage IV C-IV D (5/12, 42%). Although our data indicate that intrathecal anti-MBP Ig G may occur early during HIV-1 infection and that they are more common in patients with HIV-1-associated cognitive/motor complex, the possib le demyelinating role of these antibodies remains to be demonstrated.