i(3)so3-galactosylceramide and Acquired-Immunodeficiency-Syndrome

A 38-year-old man developed the Guillain-Barré syndrome (GBS) associated with untreated end-stage AIDS and CD4+ lymphocyte count of 3 cells/mm(3). The patient had serum high titer anti-sulfatide antibodies and responded well to infusion of immunoglobulin. The data suggest that elevated levels of anti-sulfatide antibodies may play a role in the pathogenesis of GBS in this patient, although a direct neurotropic effect of HIV virus cannot be excluded.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antibodies; CD4-Positive T-Lymphocytes; Chromatography, Thin Layer; Enzyme-Linked Immunosorbent Assay; Guillain-Barre Syndrome; Humans; Male; Neural Conduction; Peripheral Nerves; Sulfoglycosphingolipids

Cerebrospinal fluid (CSF) sulfatide concentrations were analyzed in 18 patients with asymptomatic HIV-1 infection, in 16 patients with AIDS who were free from opportunistic infections in the central nervous system (CNS), in 12 HIV-1-infected patients with opportunistic CNS infections or lymphoma, and in 19 HIV-negative controls, by thin-layer chromatography overlay technique using an antisulfatide antibody to estimate the metabolic turnover of myelin. The majority of asymptomatic HIV-1-infected patients had normal CSF sulfatide concentrations, but the mean CSF sulfatide concentration was still elevated compared to that in HIV-negative controls (152 compared to 99 nmol/liter, p < 0.05). The CSF sulfatide concentrations in the AIDS group (mean 395 nmol/liter) were significantly increased compared to those in asymptomatic HIV-1-infected patients (p < 0.01) and in HIV-negative controls (p < 0.001), but did not differ significantly between patients with and without dementia. Increased CSF sulfatide concentrations were also found in patients with opportunistic infection or lymphoma in the CNS. In the entire study population, the sulfatide levels were associated with blood-brain barrier function, but not with intrathecal immunoglobulin production or with positive HIV isolations from CSF. Thus, signs of white matter changes, measured as increased CSF sulfatide concentrations, could be found in some asymptomatic HIV-1-infected patients, but the highest levels were seen in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Blood-Brain Barrier; Brain Diseases; Cytomegalovirus; Female; HIV Antibodies; HIV-1; Humans; Immunoglobulin G; Male; Middle Aged; Myelin Sheath; Polymerase Chain Reaction; Sulfoglycosphingolipids

Peripheral nervous system involvement in the acquired immunodeficiency syndrome (AIDS) can take the form of an acute or chronic inflammatory demyelinating polyneuropathy, polyradiculopathy, mononeuropathy multiplex, or autonomic neuropathy. There is no widely held consensus on the etiology of PNS or other neurological complications associated with HIV infection. We report here that PNS disease in HIV-infected individuals is associated with intrathecal synthesis of an antibody directed against sulfatide, a major component of myelin. The anti-sulfatide antibody is also present nonspecifically in serum. The antibody requires the presence of the 3-O-sulfogalactosyl residue for binding and recognizes preferentially the hydroxy fatty acid-containing form of sulfatide. Anti-sulfatide antibodies are therefore one of the humoral factors responsible for demyelinating diseases in AIDS patients.

Topics: Acquired Immunodeficiency Syndrome; Animals; Cattle; HIV Seropositivity; Humans; Immunoglobulin G; Molecular Structure; Peripheral Nervous System Diseases; Structure-Activity Relationship; Sulfoglycosphingolipids

Characterization of a polyclonal antibody to galactosyl ceramide (Gal-Cer) which inhibits the internalization and infection of HIV-1 in neural cell lines was carried out. Polyclonal antibody to Gal-Cer was produced by injecting rabbits with Gal-Cer liposomes. The specificity of anti-Gal-Cer binding was studied by high performance thin layer chromatography (HPTLC)-based immunoassay. Using natural and semisynthetic lipids, the specificity of anti-Gal-Cer interaction was studied. The antibody bound to Gal-Cer and its derivatives. The antibody did not bind to glucosyl ceramide or lactosyl ceramide. Glucosyl ceramide differs from Gal-Cer by a hydroxyl group at the fourth carbon and in lactosyl ceramide galactose is linked to ceramide by an intervening glucose molecule. This indicates that D-galactose linked to ceramide is essential for binding. Removal of fatty acid from Gal-Cer, as seen with N-palmitoyl- and N-oleoyl Gal-Cer, had no effect on the binding. It appears that the third carbon of Gal-Cer is not involved in the binding. This is supported by the binding of anti-Gal-Cer to sulfatide or GM4 in which sulfate or sialic acid are added at the third carbon of Gal-Cer, respectively.

Topics: Acquired Immunodeficiency Syndrome; Animals; Antibodies; Antibody Specificity; Antigen-Antibody Reactions; Binding Sites, Antibody; Brain; Chromatography, High Pressure Liquid; Fluorescent Antibody Technique; Galactosides; Galactosylceramides; Glucosylceramides; HIV-1; Humans; Lactosylceramides; Lipid Metabolism; Lipids; Liposomes; Methylglucosides; Oligodendroglia; Rats; Sulfoglycosphingolipids