Cerebrospinal fluid antibodies directed against neuron-associated gangliosides in HIV-1 infection.
BACKGROUND
Loss of synapses and neurons is a common finding in HIV-1 infection. Since the in vivo infection of neurons by HIV-1 is limited, indirect factors are likely to contribute to the pathogenesis.


METHODS
We have analyzed cerebrospinal fluid (CSF) and serum samples from 25 HIV-1-infected individuals (nine with and 16 without CNS complications) and 19 HIV-negative controls with aseptic meningitis or viral encephalitis, for the presence of antibodies directed against the neuron-associated gangliosides GM1, GD1a and GD1b.


RESULTS
Positive antibody titers to > or =1 of the gangliosides were found in 13/25 HIV-1-infected patients in CSF and in 17/25 in serum. Significant correlations were found between the presence and titers of CSF antibodies against GM1, GD1a, and GD1b. Six out of nine patients with, and 3/16 without neurological complications (p < 0.05) had positive CSF titers of > or = 1 of the ganglioside antibodies combined with negative serum titers, indicating intrathecal antibody production. In contrast, only 1/19 controls had detectable anti-ganglioside antibodies in the CSF.


CONCLUSIONS
The results should be interpreted with caution and CSF anti-ganglioside antibody production might be a part of a non-specific intrathecal polyclonal immunoactivation. Nevertheless, autoantibodies directed against neuron-associated gangliosides might be involved in the neuropathogenesis in HIV-1 disease.
Gisslén
M
M
Institute of Internal Medicine, Dept of Infectious Diseases, Sahlgrenska University Hospital, Göteberg, Sweden. magnus.gisslen@infect.gu.se
Lekman
A
A
Fredman
P
P
D000328:Adult; D000906:Antibodies / Q000097:blood / Q000134:cerebrospinal fluid*; D001323:Autoantibodies / Q000097:blood / Q000134:cerebrospinal fluid; D018792:Encephalitis, Viral / Q000134:cerebrospinal fluid* / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology; D005732:Gangliosides / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid* / Q000150:complications; D015497:HIV-1; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid; D007075:Immunoglobulin M / Q000097:blood / Q000134:cerebrospinal fluid; D007783:Lactones / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000737:chemistry
D000906:Antibodies; D001323:Autoantibodies; D005732:Gangliosides; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007783:Lactones; C059248:ganglioside GD1a dilactone; C033851:ganglioside, GD1b; D005677:G(M1) Ganglioside