Immunocytochemical observations on the distribution of myelin‐associated glycoprotein and myelin basic protein in multiple sclerosis lesions

Itoyama, Yasuto; Sterhberger, Nancy H.; Webster, Henry deF.; Quarles, Richard H.; Cohen, Steven R.; Richardson, Edward P.

doi:10.1002/ana.410070212

Cited by 236 publications

(97 citation statements)

References 22 publications

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“…Since loss of MAG appears to be an early event in the development of some multiple sclerosis plaques (24)(25)(26)(27) and MAG determinants are present on lymphocytes with natural killer and T suppressor cell function, this finding may have implications for the pathogenesis of this disease. A similar suggestion by Oger et al (5) was based on oligodendrocytes and T suppressor lymphocytes sharing the (28,29), it is clear from the results described here than an antigenic determinant in MAG is shared with natural killer and some T suppressor cells.…”

Section: Discussionmentioning

confidence: 99%

Murine monoclonal antibodies to the myelin-associated glycoprotein react with large granular lymphocytes of human blood.

Dobersen¹,

Gascón²,

Trost³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Monoclonal antibodies prepared to human myelin-associated glycoprotein were shown to react with a population of human peripheral blood mononuclear cells. The population is similar to the large granular lymphocytes or natural killer cells defined by antibody Leu 7 (also called HNK-1). The population also includes cells exhibiting the Leu 2 marker for suppressor/cytotoxic T cells. The results indicate a shared antigenicity between the nervous system and the immune system and may be relevant to the pathogenesis of demyelinating diseases.Evidence has been accumulating for shared antigenic determinants between the nervous system and the immune system (1-5). This crossreactivity may be involved in the etiopathology of such neurological diseases as multiple sclerosis (5) and myasthenia gravis (3, 4). It recently has been demonstrated that Leu 7 (or HNK-1)-a mouse monoclonal antibody, raised to a human lymphoblastoma, that recognizes human natural killer cells-reacts with components of nervous tissue (6, 7). The myelin-associated glycoprotein (MAG) was identified as a molecule in nervous tissue containing the epitope recognized by this monoclonal antibody (7,8). Furthermore, the epitope in MAG is in its carbohydrate moieties (9) and also is in other glycoconjugates of peripheral nerve (9, 10).In this paper, we describe the reaction of mouse monoclonal antibodies prepared to MAG (11) with a subpopulation of human peripheral blood mononuclear cells. Further experiments show that this population is similar to the large granular lymphocytes (LGL) recognized by Leu 7. The results indicate that MAG and a population of peripheral blood lymphocytes share a common antigenic determinant. This finding may have relevance in the pathogenesis of demyelinating diseases.MATERIALS AND METHODS Monoclonal Antibodies. Murine monoclonal antibodies to MAG were produced as described (11). Briefly, P3X63-Ag8.653 myeloma cells were fused with spleen cells from a female NZB/N mouse immunized with purified human MAG isolated from the central nervous system. Hybrids and subsequent clones were screened for antibody production to MAG by using a solid-phase enzyme immunoassay system. The following monoclonal antibodies were used in this study: G7C8, E8B8, and C6D9 of the IgM subclass with K light chains, which react with determinants in the carbohydrate moieties of human MAG; F7F7, an IgG2b subclass antibody with K light chains, which also reacts with a carbohydrate determinant of human MAG; and B11F7 (IgG2b) and D7E10 (IgGl) with K light chains, which react with polypeptide determinants of human and rat MAG. The hybridomas were grown as ascites tumors in pristane-primed NIH/Swiss nude mice. Monoclonal antibodies were purified from ascites fluid by Sepharose-protein A affinity chromatography (12) for antibodies F7F7 and B11F7 and by euglobulin fractionation followed by Sephadex G-200 chromatography (13) for antibody G7C8. Hybridoma HNK-1 (14) was purchased from the American Type Culture Collection. The hybridoma was grown and the monoclonal a...

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Section: Discussionmentioning

confidence: 99%

Murine monoclonal antibodies to the myelin-associated glycoprotein react with large granular lymphocytes of human blood.

Dobersen¹,

Gascón²,

Trost³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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“…As noted previously [15], areas of myelin loss and breakdown were easily identified by absent or abnormal BP immunostaining in spinal cord sections from patients with MS. Large areas of myelin loss often included gray matter and a substantial part of the spinal cord surface (Fig 2). In sections from six of the ten patients with MS, spinal cord lesions contained myelin sheaths that were stained by Po antiserum (Fig 3; see Fig 2).…”

Section: Findings In Multiple Sclerosismentioning

confidence: 94%

Schwann cell remyelination of demyelinated axons in spinal cord multiple sclerosis lesions

Itoyama

Webster

Richardson

et al. 1983

Annals of Neurology

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127

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To investigate remyelination in multiple sclerosis lesions, we immunostained spinal cord sections from patients with multiple sclerosis and neurological normal (control) patients with antisera to P0 protein, a major constituent of peripheral nervous system myelin, and myelin basic protein, which is found in both central and peripheral nervous system myelin. In sections from five of the eight patients with no clinical or pathological evidence of neurological disease, P0 immunostaining was confined to peripheral myelin sheaths in dorsal and ventral roots. They were intensely stained, and peripheral--central nervous system transition zones were clearly demarcated. Sections from the other three control patients contained a few P0-stained sheaths in the central nervous system near root entry zones or among marginal glia near the dorsal sulcus. Spinal cord sections from six of the ten patients with multiple sclerosis contained clusters of myelin sheaths immunostained by P0 antiserum. These regenerating sheaths of peripheral nervous system origin were most numerous in large lesions and were commonly located in central areas or peripherally near root entry zones. The sheaths were observed frequently in areas of active demyelination and appeared morphologically normal even when surrounded by debris-filled macrophages. Near margins of small inactive plaques were a few basic protein--stained oligodendroglia extending processes to thin basic protein--stained sheaths.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…To achieve maximal sensitivity in detecting GM demyelination MBP immunohistochemistry was used in addition to routine Luxol fast blue staining (30). Areas of complete myelin loss were traced manually on three sections per block using Image Pro-Plus 6.0 software and their surface areas measured and averaged.…”

Section: Quantification Of Demyelinationmentioning

confidence: 99%

Substantial Archaeocortical Atrophy and Neuronal Loss in Multiple Sclerosis

Papadopoulos¹,

Dukes²,

Patel³

et al. 2009

Brain Pathology

176

196

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Recent studies have revealed extensive neocortical pathology in multiple sclerosis (MS). The hippocampus is a unique archaeocortical structure understudied in MS. It plays a central role in episodic and anterograde memory-the most frequently impaired cognitive modalities in MS. This histopathological study aimed to investigate inflammatory demyelination and neurodegenerative changes in the MS archaeocortex. A detailed quantitative analysis was performed on hippocampal autopsy tissue from 45 progressive MS cases and seven controls. Forty-one lesions were identified in 28 of the 45 hippocampal MS-blocks examined, with percentage area of demyelination averaging 30.4%. The majority of lesions were chronic and subpially or subependymally located. Compared to controls, neuronal numbers were decreased by 27% in CA1 and 29.7% in CA3-2. Furthermore, the size of neurones was decreased by 17.4% in CA1. There was evidence of gross hippocampal atrophy with a 22.3% reduction in the average cross-sectional area, which correlated with neuronal loss. Our study provides evidence of substantial archaeocortical pathology largely resembling patterns seen in the neocortex and suggests that hippocampal involvement could contribute to memory impairments often seen in MS.

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Immunocytochemical observations on the distribution of myelin‐associated glycoprotein and myelin basic protein in multiple sclerosis lesions

Cited by 236 publications

References 22 publications

Murine monoclonal antibodies to the myelin-associated glycoprotein react with large granular lymphocytes of human blood.

Murine monoclonal antibodies to the myelin-associated glycoprotein react with large granular lymphocytes of human blood.

Schwann cell remyelination of demyelinated axons in spinal cord multiple sclerosis lesions

Substantial Archaeocortical Atrophy and Neuronal Loss in Multiple Sclerosis

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