Title |
Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid cause demyelination of spinal cord explants
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Published in |
Acta Neuropathologica, October 2015
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DOI | 10.1007/s00401-015-1500-6 |
Pubmed ID | |
Authors |
Kevin Blauth, John Soltys, Adeline Matschulat, Cory R. Reiter, Alanna Ritchie, Nicholas L. Baird, Jeffrey L. Bennett, Gregory P. Owens |
Abstract |
B cells are implicated in the etiology of multiple sclerosis (MS). Intrathecal IgG synthesis, cerebrospinal fluid (CSF) oligoclonal bands and lesional IgG deposition suggest a role for antibody-mediated pathology. We examined the binding of IgG1 monoclonal recombinant antibodies (rAbs) derived from MS patient CSF expanded B cell clones to central nervous system (CNS) tissue. MS rAbs displaying CNS binding to mouse and human CNS tissue were further tested for their ability to induce complement-mediated tissue injury in ex vivo spinal cord explant cultures. The staining of CNS tissue, primary human astrocytes and human neurons revealed a measurable bias in MS rAb binding to antigens preferentially expressed on astrocytes and neurons. MS rAbs that recognize myelin-enriched antigens were rarely detected. Both myelin-specific and some astrocyte/neuronal-specific MS rAbs caused significant myelin loss and astrocyte activation when applied to spinal cord explant cultures in the presence of complement. Overall, the intrathecal B cell response in multiple sclerosis binds to both glial and neuronal targets and produces demyelination in spinal cord explant cultures implicating intrathecal IgG in MS pathogenesis. |
X Demographics
Geographical breakdown
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 96 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 16 | 17% |
Researcher | 11 | 11% |
Student > Master | 9 | 9% |
Student > Bachelor | 8 | 8% |
Other | 8 | 8% |
Other | 17 | 18% |
Unknown | 27 | 28% |
Readers by discipline | Count | As % |
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Neuroscience | 17 | 18% |
Medicine and Dentistry | 15 | 16% |
Agricultural and Biological Sciences | 9 | 9% |
Biochemistry, Genetics and Molecular Biology | 7 | 7% |
Immunology and Microbiology | 6 | 6% |
Other | 7 | 7% |
Unknown | 35 | 36% |