| 1. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
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Increased cerebrospinal fluid ganglioside GD3 concentrations as a marker of microglial activation in HIV type 1 infection
- 1998
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Ingår i: AIDS Res Hum Retroviruses. ; 14:12, s. 1065-9
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Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) early in the infectious course. The predominant, productively infected cell type within the CNS is the microglial cell. We have analyzed the cerebrospinal fluid (CSF) levels of the ganglioside GD3, a microglia/macrophage and astrocyte marker, in 22 HIV-1-infected individuals at different stages of the disease, and in 44 age-matched HIV-negative, healthy controls. To distinguish between microglial/macrophage and astroglial involvement, the GD3 levels were compared with CSF levels of the glial fibrillary acidic protein (GFAp), which is expressed exclusively in astrocytes. A significantly higher mean CSF concentration of GD3 was found in HIV-1-infected patients compared to controls (56.7 and 40.1 nmol/L, respectively, p < 0.001). Seven of 22 HIV-1-infected patients had increased CSF levels of GD3 (above mean + 2 SD in controls), all but one of these had normal levels of GFAp, indicating a microglial activation or proliferation as the major source of the increased GD3 levels.
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| 2. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Cerebrospinal fluid antibodies directed against neuron-associated gangliosides in HIV-1 infection
- 2000
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Ingår i: Infection. ; 28:3, s. 143-8
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Tidskriftsartikel (refereegranskat)abstract
- 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. PATIENTS AND 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. CONCLUSION: 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.
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| 3. |
- Gisslén, Magnus, 1962, et al.
(författare)
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High levels in serum, but no signs of intrathecal synthesis of anti-sulfatide antibodies in HIV-1 infected individuals with or without central nervous system complications
- 1999
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Ingår i: J Neuroimmunol. ; 94:1-2, s. 153-6
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Tidskriftsartikel (refereegranskat)abstract
- Myelin degeneration is commonly found in the central nervous system (CNS) of individuals infected with human immunodeficiency virus type 1 (HIV-1), especially in patients with HIV-1-associated dementia. We analysed cerebrospinal fluid (CSF) and serum samples from 25 HIV-1 infected individuals for the presence of antibodies directed against sulfatide, the major acidic glycosphingolipid in myelin. Nine of the patients had CNS complications, including 3 with HIV-1-associated dementia, and 16 had no neurological symptoms. Elevated titres of anti-sulfatide antibodies were found in serum from 24/25 HIV-1-infected individuals but in none of them in the CSF. Although the vast majority of HIV-1-infected individuals harbour autoantibodies directed against sulfatide in serum, the lack of detectable intrathecal production indicates that anti-sulfatide antibodies are not a major component in the pathogenesis of CNS myelin damage in HIV-1 infection.
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| 4. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Increased cerebrospinal fluid ganglioside GM1 concentrations indicating neuronal involvement in all stages of HIV-1 infection
- 1997
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Ingår i: J Neurovirol. ; 3:2, s. 148-52
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Tidskriftsartikel (refereegranskat)abstract
- 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. Conclusion: 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.
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| 5. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Temporarily controlled HIV-1 replication after intravenous immunoglobulin treatment of Guillain-Barre syndrome
- 2005
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Ingår i: Scand J Infect Dis. - : Informa UK Limited. - 0036-5548. ; 37:11-12, s. 877-81
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Tidskriftsartikel (refereegranskat)abstract
- HIV establishes a latent infection in resting CD4(+) T-lymphocytes. A possible strategy to eliminate cellular reservoirs in long-lived, HIV-1-infected quiescent CD4(+) T-lymphocytes might be to add T-cell-activating agents to potent antiretroviral therapy. In this report we describe a patient with Guillain-Barre syndrome treated with high dose intravenous immunoglobulin (IVIG) in addition to antiretroviral therapy. A transiently increased viral load and immunoactivation during the IVIG treatment suggest activation of latently infected cells and increased turnover rate of the latent viral reservoir. HIV replication was controlled with plasma viral load <20 copies/ml, for at least 3 months after antiretroviral treatment interruption. CSF neural markers reflecting degenerative processes in the brain during the symptomatic period and follow-up were also analysed. Very high CSF sulfatide concentrations were found indicating that the pathology involves severe demyelination.We hypothesize that IVIG in this case contributed to an activation of latently infected cells, which led to a transient increase in plasma HIV-1 RNA during the IVIG treatment and a long period of undetectable viral load after antiretroviral treatment interruption. Further, this is the first time, to our knowledge, that detailed CSF findings are described in HIV-1 associated GBS.
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| 6. |
- Haghighi, Sara, et al.
(författare)
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Increased CSF sulfatide levels and serum glycosphingolipid antibody levels in healthy siblings of multiple sclerosis patients
- 2013
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 326:1-2, s. 35-39
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Tidskriftsartikel (refereegranskat)abstract
- A proportion of healthy siblings of multiple sclerosis (MS) patients have an oligodonal immunological reaction in their cerebrospinal fluid (CSF) termed the "MS oligoclonal trait". The CSF levels of the major myelin glycosphingolipid sulfatide and serum antibodies against the glycosphingolipids sulfatide and galactosylceramide were recently reported to be increased in MS patients. We studied the levels of these substances in pairs of 46 patients and their 46 healthy siblings and 50 unrelated healthy blood donors (HBD). The sulfatide concentration in CSF was assayed by thin layer chromatography and immunostaining, and the concentration of galactosylceramide by densitometry after thin layer chromatography. Anti-glycosphingolipid antibody levels were assayed by ELISA. In the healthy siblings, the CSF sulfatide concentrations were markedly increased (p<0.001, age adjusted p = 0.025), and the serum IgM anti-GalCer antibodies were increased in healthy siblings compared with HBD (p = 0.02). The increased sulfatide or antibody levels did not co-segregate with the "MS oligoclonal trait" or the HLA-DR15 phenotype. In conclusion, a proportion of healthy siblings of MS patients have increased CSF sulfatide and anti-glycosphingolipid antibody levels, which may, analogous to the "MS oligoclonal trait", constitute an "MS glycosphingolipid endophenotype". Endophenotypes could potentially simplify the genetics of complex disorders
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| 7. |
- Haghighi, Sara, et al.
(författare)
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Myelin glycosphingolipid immunoreactivity and CSF levels in multiple sclerosis.
- 2012
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 125:1, s. 64-70
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Tidskriftsartikel (refereegranskat)abstract
- Objectives- Patients with multiple sclerosis were reported to harbour antibodies not only against proteins and glycoproteins but also against glycolipids, including sulfatide and galactosylceramide (GalCer), the two major glycosphingolipids of myelin. However, previous results were inconsistent concerning glycosphingolipid levels, antibody type, dominance of serum or Cerebrospinal fluid compartments and relationship to the multiple sclerosis (MS) course. Results- We hereby report that the cerebrospinal fluid levels of sulfatide were increased in patients with MS (n=46) compared with controls (n=50, P<0.001). In addition, patients had higher serum IgM anti-glycosphingolipid titres than controls (P=0.03 for sulfatide, <0.001 for GalCer), while the anti-glycosphingolipid IgM antibodies in the cerebrospinal fluid were essentially normal. However, in seven of 46 patients cerebrospinal fluid IgG antibodies against GalCer (P=0.004) could be detected, which was not found in any of the control individuals, and this finding might mirror the occurrence of more specific B-cell clones behind the blood-brain barrier. Conclusions- The IgM immunoreactivity in serum did not show any relationship to the type of course or severity of MS, arguing against a phenomenon secondary to myelin damage. Thus, the IgM antibody findings are compatible with an early antigen challenge or autoimmunity associated with natural antibodies.
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| 8. |
- Kristjánsdóttir, Ragnhildur, et al.
(författare)
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Cerebrospinal fluid markers in children with cerebral white matter abnormalities.
- 2001
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Ingår i: Neuropediatrics. - : Georg Thieme Verlag KG. - 0174-304X .- 1439-1899. ; 32:4, s. 176-82
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Tidskriftsartikel (refereegranskat)abstract
- Disorders of the cerebral white matter in children constitute a heterogeneous group and the diagnostic work is often complicated. Clinical and radiological characteristics can provide diagnostic clues but there is a need for further diagnostic methods. This study focused on assessing neurochemical "markers" in the cerebrospinal fluid considered to reflect damage to white matter components such as myelin and glial cells as well as neurones with their axons and synapses. The aim was to evaluate whether they contributed to the elucidation of pathogenic processes and the direction of further diagnostic efforts. Seventeen of the 26 cases had increased levels of the glial cell marker ganglioside GD3, indicating gliosis, or of the CNS myelin marker sulfatide, indicating myelin disturbance. As signs of disturbed maturation or sustenance, the nerve cell markers GD1 b, GT1 b and total gangliosides were reduced, as was the synapse marker GD1a. Increased 5-HIAA indicated increased serotonergic turnover. Children with an increased level of the axonal marker Tau protein had a progressive disease whereas GD1a was reduced in the progressive group (n = 11). In contrast, GD3 and HVA were increased in the non-progressive group (n = 15). The chemical profiles were found to be useful, in combination with clinical and radiological findings, when investigating children with white matter abnormalities.
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| 9. |
- Nordin, Viviann, et al.
(författare)
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Gangliosides in cerebrospinal fluid in children with autism spectrum disorders.
- 1998
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Ingår i: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 40:9, s. 587-594
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Tidskriftsartikel (refereegranskat)abstract
- Gangliosides are sialic acid-containing glycolipids found in all cells, especially abundant in nerve cells and mainly situated on outer-membrane surfaces. The aim of this study was to provide data on the concentration of gangliosides in the CSF of children and adolescents with autism spectrum disorders (ASD) - 66 with autistic disorder, and 19 with other autism spectrum disorders. The comparison group consisted of 29 children and adolescents, whose CSF had been sampled to exclude acute infectious CNS disorder. The concentrations of the gangliosides GM1, GD1a, GD1b, and GT1b were determined using a microimmunoaffinity technique. The ASD group had a significantly higher concentration of ganglioside GM1 compared with the comparison group. The GM1 increase could not be explained as secondary to other clinical factors. Mean ganglioside levels did not differentiate subgroups with autistic disorder and those with a more atypical clinical picture, nor subgroups with known medical disorders and those with idiopathic autism. Altered patterns of gangliosides in the CNS might reflect important correlates of pathogenesis in autism.
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| 10. |
- Tullberg, Mats, 1965, et al.
(författare)
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CSF sulfatide distinguishes between normal pressure hydrocephalus and subcortical arteriosclerotic encephalopathy.
- 2000
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 0022-3050. ; 69:1, s. 74-81
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Tidskriftsartikel (refereegranskat)abstract
- To examine the CSF concentrations of molecules reflecting demyelination, neuronal and axonal degeneration, gliosis, monoaminergic neuronal function, and aminergic and peptidergic neurotransmission in a large series of patients with normal pressure hydrocephalus (NPH) or subcortical arteriosclerotic encephalopathy (SAE), to elucidate pathogenic, diagnostic, and prognostic features.CSF concentrations of glycosphingolipid (sulfatide), proteins (neurofilament triplet protein (NFL), glial fibrillary acidic protein (GFAP)), neuropeptides (vasoactive intestinal peptide (VIP), 4-aminobutyric acid (GABA)), and monoamines (homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenylglycol (HMPG)) were analysed in 43 patients with NPH and 19 patients with SAE. The diagnoses of NPH and SAE were based on strict criteria and patients with NPH were subsequently operated on. Twelve clinical variables, psychometric tests measuring perceptual speed, accuracy, learning, and memory and a psychiatric evaluation were performed in all patients and before and after a shunt operation in patients with NPH.The CSF sulfatide concentration was markedly increased in patients with SAE (mean 766, range 300-3800 nmol/l) compared with patients with NPH (mean 206, range 50-400 nmol/l) (p<0.001). 5-HIAA, GABA, and VIP in CSF were higher in patients with SAE than in patients with NPH. The patients with NPH with cerebrovascular aetiology had higher sulfatide concentrations and a poorer outcome after shunt surgery than patients with NPH with other aetiologies.The pathogenesis of the white matter changes in NPH and SAE is different and ischaemic white matter changes can be a part of the NPH state. The markedly increased CSF sulfatide concentrations in patients with SAE indicate ongoing demyelination as an important pathophysiological feature of SAE. The CSF sulfatide concentration distinguished between patients with SAE and those with NPH with a sensitivity of 74% and a specificity of 94%, making it an important diagnostic marker.
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| 11. |
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