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Novel astrocytic protein in multiple sclerosis plaques
S K Malhotra1, R Predy, E S Johnson
1Department of Zoology, University of Alberta, Edmonton, Canada.
Abstract:
Monoclonal antibody J1-31 (MAb J1-31, isotype IgG 2b) was raised against crude homogenate of brain tissue from a multiple sclerosis (MS) patient (autopsy sample; Malhotra et al.: Microbios Letters 26:151-157, 1984). In human brain, MAb J1-31 recognizes an intracellular protein antigen (J1-31 antigen), which bands at approximately 30,000 daltons under reducing conditions for sodium dodecyl sulfate gel electrophoresis (Singh et al.: Bioscience Reports 6:73-79, 1986). By immunofluorescence microscopy, MAb J1-31 stains those cells that are also stained by antiserum to glial fibrillary acidic protein (GFAP), namely astrocytes, retinal Müller cells, and tanycytes in the ependyma (Predy et al.: Bioscience Reports 7:491-502, 1987). In addition, MAb J1-31 stains ciliated ependymal cells that do not express GFAP. Using a model system for gliosis (laceration-type injury of rat spinal cord), we were able to show that astrocytes responding to central nervous system injury exhibit greatly enhanced staining for J1-31 antigen (Predy et al.: Journal of Neuroscience Research 19:397-404, 1988; Predy and Malhotra: Brain Research Bulletin in press, 1989). In this article, we demonstrate that immunofluorescence staining owing to MAb J1-31 is greatly enhanced in MS plaques, as compared to adjacent "apparently normal" white matter. (This is consistent with previous results as MS plaques characteristically show an astroglial response [reactive gliosis] leading to the formation of a glial scar [McKhann: Annual Review of Neuroscience 5:219-239, 1982].) In addition, we present further evidence that J1-31 antigen is distinct from GFAP, although these two proteins may be associated spatially with one another.
Insights
Monoclonal antibody J1-31 detects an intracellular antigen in the brain. This J1-31 antigen is significantly elevated in multiple sclerosis plaques, indicating its potential role in reactive gliosis.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Monoclonal antibody J1-31 (MAb J1-31) targets an intracellular protein antigen in human brain.
- The J1-31 antigen is recognized in astrocytes, retinal Müller cells, and ependymal cells.
- Previous studies showed enhanced J1-31 antigen staining in astrocytes responding to central nervous system injury.
Purpose of the Study:
- To investigate the expression of J1-31 antigen in multiple sclerosis (MS) plaques.
- To compare J1-31 antigen staining in MS plaques versus normal-appearing white matter.
- To further elucidate the relationship between J1-31 antigen and glial fibrillary acidic protein (GFAP).
Main Methods:
- Immunofluorescence microscopy was used to detect J1-31 antigen.
- Staining patterns of MAb J1-31 were analyzed in MS brain tissue.
- Comparison of J1-31 antigen staining with GFAP staining.
Main Results:
- Immunofluorescence staining for J1-31 antigen was significantly enhanced in MS plaques compared to adjacent white matter.
- This enhanced staining in MS plaques is consistent with reactive gliosis.
- Evidence suggests J1-31 antigen is distinct from GFAP, though spatially associated.
Conclusions:
- J1-31 antigen expression is upregulated in MS plaques, correlating with reactive astrogliosis.
- MAb J1-31 serves as a marker for cellular responses in MS.
- The J1-31 antigen represents a potential target for understanding MS pathogenesis.