g(m1)-ganglioside and HIV-Infections

Guillain-Barré syndrome sometimes manifests as immune reconstitution inflammatory syndrome. We report a treatment-naïve male with chronic HIV-1 infection who presented with an axonal variant of Guillain-Barré syndrome. Antiretroviral therapy commenced one month later and no rapid improvement or deterioration of tetraparesis was noted. This is the first report that describes the detection and serial measurements of anti-ganglioside antibody in a patient with HIV infection. This case suggests a limited role for T-cell immunity in the production of anti-ganglioside antibody and the pathogenesis of axonal variants, since the antiretroviral therapy-induced improvement in T-cell immunity neither re-elevated anti-ganglioside antibody titer nor worsened tetraparesis.

Topics: Adult; Anti-Retroviral Agents; G(M1) Ganglioside; Guillain-Barre Syndrome; HIV Infections; HIV-1; Humans; Immunoglobulin G; Male

T cell polarization and redistribution of cellular components are critical to processes such as activation, migration, and potentially HIV infection. Here, we investigate the effects of CD4 engagement on the redistribution and localization of chemokine receptors, CXCR4 and CCR5, adhesion molecules, and lipid raft components including cholesterol, GM1, and glycosyl-phosphatidylinositol (GPI)-anchored proteins. We demonstrate that anti-CD4-coated beads (alpha CD4-B) rapidly induce co-capping of chemokine receptors as well as GPI-anchored proteins and adhesion molecules with membrane cholesterol and lipid rafts on human T cell lines and primary T cells to the area of bead-cell contact. This process was dependent on the presence of cellular cholesterol, cytoskeletal reorganization, and lck signaling. Lck-deficient JCaM 1.6 cells failed to cap CXCR4 or lipid rafts to alpha CD4-B. Biochemical analysis reveals that CXCR4 and LFA-1 are recruited to lipid rafts upon CD4 but not CD45 engagement. Furthermore, we also demonstrate T cell capping of both lipid rafts and chemokine receptors at sites of contact with HIV-infected cells, despite the binding of an HIV inhibitory mAb to CXCR4. We conclude that cell surface rearrangements in response to CD4 engagement may serve as a means to enhance cell-to-cell signaling at the immunological synapse and modulate chemokine responsiveness, as well as facilitate HIV entry and expansion by synaptic transmission.

Topics: CD4 Antigens; Cell Adhesion Molecules; Cell Aggregation; Cell Communication; Cell Polarity; Cholesterol; G(M1) Ganglioside; Glycosylphosphatidylinositols; HIV Infections; HIV-1; Humans; Jurkat Cells; Lymphocyte Activation; Lymphocyte Function-Associated Antigen-1; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Membrane Microdomains; Protein Transport; Receptors, CCR5; Receptors, Chemokine; Receptors, CXCR4; Signal Transduction; T-Lymphocytes

Measurements of cerebrospinal fluid (CSF) concentrations of gangliosides can be used as markers of central nervous system (CNS) neuronal involvement. We have analysed the CSF concentrations of the four major brain gangliosides GM1, GD1a, GD1b, and GT1b at different stages of HIV-1 infection. CSF samples were collected from 44 HIV-1-infected patients and from 24 HIV-negative, healthy controls. A significantly higher mean CSF concentration of the ganglioside GM1 was found in HIV-1-infected patients than in HIV-negative controls (27 and 19 nmol/l, respectively, P<0.01). The HIV-infected patients also had a higher mean GM1 proportion of the total ganglioside concentration (11% compared with 8.5%, P < 0.01). Nine out of 27 patients with asymptomatic HIV-1 infection, three of ten with AIDS without neurological complications, and three of seven with AIDS dementia complex had CSF GM1 concentrations above the mean+2SD in the HIV-negative control group.. Biochemical signs of ongoing neuronal involvement could be found in about one third of HIV-1-infected patients. The same frequency was found regardless of stage, although the highest levels of CSF gangliosides were found in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS Dementia Complex; Disease Progression; G(M1) Ganglioside; Gangliosides; HIV Infections; Humans

Natural killer (NK) cells in HIV-infected patients have a reduced ability to generate non-MHC restricted cytotoxicity to a variety of target cells. The authors investigated antibodies to NK cells in HIV-infected patients and evaluated effects of these antibodies to NK cell numbers and function. Antibodies to NK cells were determined in 160 HIV-infected patients and 35 healthy controls. Flow cytometric whole blood methods were developed to detect antibodies to NK cells. Antibodies to asialo-GM1 were detected by TLC immunostaining. The presence of antibodies to NK cells was demonstrated in plasma of about one-third (54/160) of HIV-infected patients but rarely in controls (2/35). Auto-antibodies bound to NK cells in vivo and were detected by a strong increase of surface immunoglobulin (Ig) on NK cells of HIV-infected patients. Anti-NK cell antibodies were warmreactive antibodies rather of IgG than of IgM phenotype. The prevalence of specific antibodies to asialo-GM1 was low (12.5%). Numbers of circulating NK cells did not differ significantly between antibody positive (99.5/microliters) and antibody negative (141/microliters) patients (P = 0.3). However, pre-incubation of healthy donors' NK cells with autoantibody positive plasma significantly inhibited cytotoxicity to K562 leukaemic cells (P = 0.002). Autoantibodies to NK cells in HIV-infected patients are present in the plasma of one-third of HIV-infected patients and are bound to NK cells in vivo. There is evidence that these autoantibodies can induce NK cell defects similar to those seen in vivo.

Topics: Antibodies, Anti-Idiotypic; Antibody-Dependent Cell Cytotoxicity; Autoantibodies; Blood Cell Count; G(M1) Ganglioside; HIV Infections; Humans; Killer Cells, Natural; Receptors, Antigen, B-Cell; Receptors, IgG