Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1–anchored membrane domains
B cell clonal expansion and cerebrospinal fluid (CSF) oligoclonal IgG bands are established features of the immune response in multiple sclerosis (MS). Clone-specific recombinant monoclonal IgG1 Abs (rAbs) derived from MS patient CSF plasmablasts bound to conformational proteolipid protein 1 (PLP1)...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2023-10-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI162731 |
| _version_ | 1797634431454806016 |
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| author | Gregory P. Owens Timothy J. Fellin Adeline Matschulat Vanessa Salas Kristin L. Schaller Katherine S. Given Alanna M. Ritchie Andre Navarro Kevin Blauth Ethan G. Hughes Wendy B. Macklin Jeffrey L. Bennett |
| author_facet | Gregory P. Owens Timothy J. Fellin Adeline Matschulat Vanessa Salas Kristin L. Schaller Katherine S. Given Alanna M. Ritchie Andre Navarro Kevin Blauth Ethan G. Hughes Wendy B. Macklin Jeffrey L. Bennett |
| author_sort | Gregory P. Owens |
| collection | DOAJ |
| description | B cell clonal expansion and cerebrospinal fluid (CSF) oligoclonal IgG bands are established features of the immune response in multiple sclerosis (MS). Clone-specific recombinant monoclonal IgG1 Abs (rAbs) derived from MS patient CSF plasmablasts bound to conformational proteolipid protein 1 (PLP1) membrane complexes and, when injected into mouse brain with human complement, recapitulated histologic features of MS pathology: oligodendrocyte cell loss, complement deposition, and CD68+ phagocyte infiltration. Conformational PLP1 membrane epitopes were complex and governed by the local cholesterol and glycolipid microenvironment. Abs against conformational PLP1 membrane complexes targeted multiple surface epitopes, were enriched within the CSF compartment, and were detected in most MS patients, but not in inflammatory and noninflammatory neurologic controls. CSF PLP1 complex Abs provide a pathogenic autoantibody biomarker specific for MS. |
| first_indexed | 2024-03-11T12:07:39Z |
| format | Article |
| id | doaj.art-5c9b85e85c2341ef917d380b1f3354df |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:07:39Z |
| publishDate | 2023-10-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-5c9b85e85c2341ef917d380b1f3354df2023-11-07T16:20:55ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-10-0113319Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1–anchored membrane domainsGregory P. OwensTimothy J. FellinAdeline MatschulatVanessa SalasKristin L. SchallerKatherine S. GivenAlanna M. RitchieAndre NavarroKevin BlauthEthan G. HughesWendy B. MacklinJeffrey L. BennettB cell clonal expansion and cerebrospinal fluid (CSF) oligoclonal IgG bands are established features of the immune response in multiple sclerosis (MS). Clone-specific recombinant monoclonal IgG1 Abs (rAbs) derived from MS patient CSF plasmablasts bound to conformational proteolipid protein 1 (PLP1) membrane complexes and, when injected into mouse brain with human complement, recapitulated histologic features of MS pathology: oligodendrocyte cell loss, complement deposition, and CD68+ phagocyte infiltration. Conformational PLP1 membrane epitopes were complex and governed by the local cholesterol and glycolipid microenvironment. Abs against conformational PLP1 membrane complexes targeted multiple surface epitopes, were enriched within the CSF compartment, and were detected in most MS patients, but not in inflammatory and noninflammatory neurologic controls. CSF PLP1 complex Abs provide a pathogenic autoantibody biomarker specific for MS.https://doi.org/10.1172/JCI162731AutoimmunityNeuroscience |
| spellingShingle | Gregory P. Owens Timothy J. Fellin Adeline Matschulat Vanessa Salas Kristin L. Schaller Katherine S. Given Alanna M. Ritchie Andre Navarro Kevin Blauth Ethan G. Hughes Wendy B. Macklin Jeffrey L. Bennett Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1–anchored membrane domains The Journal of Clinical Investigation Autoimmunity Neuroscience |
| title | Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1–anchored membrane domains |
| title_full | Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1–anchored membrane domains |
| title_fullStr | Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1–anchored membrane domains |
| title_full_unstemmed | Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1–anchored membrane domains |
| title_short | Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1–anchored membrane domains |
| title_sort | pathogenic myelin specific antibodies in multiple sclerosis target conformational proteolipid protein 1 anchored membrane domains |
| topic | Autoimmunity Neuroscience |
| url | https://doi.org/10.1172/JCI162731 |
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