Increased circulating T cell reactivity to GM3 and GQ1b gangliosides in primary progressive multiple sclerosis

Pender, Michael P.; Csurhes, Peter A.; Wolfe, Nigel; Hooper, Kaye D.; Good, Michael F.; McCombe, Pamela A.; Greer, Judith M.

doi:10.1016/s0967-5868(02)00270-9

Cited by 53 publications

(33 citation statements)

References 35 publications

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“…Indeed, the T cell reactivity against GM1 tended to be lower in patients with other neuropathies than in healthy controls, as we have previously reported for T cell reactivity to gangliosides in patients with central nervous system diseases other than multiple sclerosis. 20 Elevated T cell reactivity to GM1 in GBS patients is congruent with previous reports of elevated anti-GM1 antibodies in patients with either demyelinating or axonal forms of GBS.…”

Section: Discussionsupporting

confidence: 88%

Increased circulating T cell reactivity to GM1 ganglioside in patients with Guillain–Barré syndrome

Csurhes

Sullivan

Green

et al. 2005

Journal of Clinical Neuroscience

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This study was performed to determine whether increased ganglioside-specific T cell reactivity can be detected in the peripheral blood of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). T cell responsiveness to the gangliosides GM1, GM3, GD1a, GD1b, GD3, GT1b, GQ1b and sulphatide was assessed in peripheral blood mononuclear cells from untreated GBS patients (57), CIDP patients (43), patients with other peripheral neuropathies (55) and healthy control subjects (74) in a standard 6-day proliferation assay. Increased T cell reactivity to GM1 occurred in GBS patients compared to healthy controls and patients with other neuropathies. There was increased reactivity to GM3 in GBS patients compared to patients with other neuropathies but not compared to healthy controls. The frequencies of increased T cell reactivity to GM1 and GM3 in CIDP patients were intermediate between those of GBS patients and controls. We suggest that T cell reactivity to gangliosides might play a contributory role in the pathogenesis of GBS and perhaps CIDP.

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Section: Discussionsupporting

confidence: 88%

Increased circulating T cell reactivity to GM1 ganglioside in patients with Guillain–Barré syndrome

Csurhes

Sullivan

Green

et al. 2005

Journal of Clinical Neuroscience

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“…In MS, the distribution of demyelinated lesions in the CNS can vary from one patient to another, and there is currently no way of predicting where they will develop. Although many studies have previously looked for myelin-Ag-specific T cell responses in patients with MS (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23), only two studies have attempted to correlate T cell autoreactivity to one (24) or several myelin proteins (25) with the distribution of lesions. One investigated reactivity to myelin proteolipid protein (PLP) epitopes by T cells from 10 patients with monocentric monophasic demyelinating syndromes suggestive of a first attack of MS (24), and the other (25) compared immunoreactivity to PLP, myelin basic protein (MBP), and myelin/oligodendrocyte glycoprotein (MOG) in 10 Japanese patients with the optico-spinal form of MS and 11 patients with conventional MS.…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

Correlation of Blood T Cell and Antibody Reactivity to Myelin Proteins with HLA Type and Lesion Localization in Multiple Sclerosis

Greer

Csurhes

Muller

et al. 2008

The Journal of Immunology

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS. The numbers of autoimmune T cells and Abs specific for proteins of CNS myelin are increased in the blood in some patients with MS. The aim of this study was to investigate whether there are correlations between the specificity of the autoimmune responses in the blood, the HLA molecules carried by the patient, and the clinical features of MS, because studies on experimental autoimmune encephalomyelitis, an animal model of MS, indicate that autoimmune responses targeting particular myelin proteins and the genetic background of the animal play a role in determining the pattern of lesion distribution. We tested blood T cell immunoreactivity to myelin proteins in 100 MS patients, 70 healthy controls, and 48 patients with other neurological disorders. Forty MS patients had strongly increased T cell reactivity to one or more myelin Ags. In these 40 patients, the most robust correlation was between CD4+ T cell reactivity to myelin proteolipid protein residues 184–209 (PLP184–209) and development of lesions in the brainstem and cerebellum. Furthermore, carriage of HLA-DR4, -DR7, or -DR13 molecules by MS patients correlated with increased blood T cell immunoreactivity to PLP184–209, as well as the development of lesions in the brainstem and cerebellum. Levels of PLP190–209-specific Abs in the blood also correlated with the presence of cerebellar lesions. These findings show that circulating T cells and Abs reactive against specific myelin Ags can correlate with lesion distribution in MS and suggest that they are of pathogenic relevance.

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“…Gadolinium-enhancing MRI brain lesions occur much less frequently in primary progressive MS than in secondary progressive MS10 and relapsing-remitting MS, 21 indicating that there is less inflammation in the brain in primary progressive MS. Histological studies have shown less perivascular lymphocytic cuffing and parenchymal inflammatory cell infiltration in the CNS in primary progressive MS than in secondary progressive MS. 28 Immunological studies have shown increased blood T-cell reactivity to the 184-209 region of myelin proteolipid protein in relapsing-remitting MS and secondary progressive MS, but not in primary progressive MS, 29 although T-cell reactivity to the gangliosides GM3 and GQ1b is increased in primary progressive MS. 30 Furthermore, blood leukocyte expression of adhesion molecules, which have a role in the trafficking of circulating leukocytes into the CNS, is different between primary progressive MS and relapsing-remitting/secondary progressive MS.…”

Section: Pathogenesis Of Primary Progressive Ms Inflammationmentioning

confidence: 99%

The pathogenesis of primary progressive multiple sclerosis: antibody-mediated attack and no repair?

Pender

2004

Journal of Clinical Neuroscience

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Primary progressive multiple sclerosis (MS) differs from the more common form of MS which has an initial relapsing-remitting course in a number of ways, including pathological features, clinical course, differential diagnosis and response to treatment. The lesions in primary progressive MS tend to be more diffuse, less inflammatory and less likely to remyelinate than those occurring in relapsing-remitting MS and secondary progressive MS; there are also fewer focal lesions in the brain in primary progressive MS. Recent evidence suggests that antibodies to central nervous system (CNS) antigens have an important role in disease progression. Such antibodies could cause demyelination, inhibit remyelination and cause axonal destruction. Ongoing immune attack by autoantibody and lack of CNS repair could be responsible for the gradually increasing disability in primary progressive MS. Further research on the B-cell and autoantibody response in primary progressive MS might lead to advances in diagnosis and treatment. Inhibition of autoantibody production by inducing B-cell apoptosis with rituximab is a potential new therapy for primary progressive MS.

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Increased circulating T cell reactivity to GM3 and GQ1b gangliosides in primary progressive multiple sclerosis

Cited by 53 publications

References 35 publications

Increased circulating T cell reactivity to GM1 ganglioside in patients with Guillain–Barré syndrome

Increased circulating T cell reactivity to GM1 ganglioside in patients with Guillain–Barré syndrome

Correlation of Blood T Cell and Antibody Reactivity to Myelin Proteins with HLA Type and Lesion Localization in Multiple Sclerosis

The pathogenesis of primary progressive multiple sclerosis: antibody-mediated attack and no repair?

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