A Distinct Class of Antibodies May Be an Indicator of Gray Matter Autoimmunity in Early and Established Relapsing Remitting Multiple Sclerosis Patients
| Autor: | Melania Spadaro, Alyssa A. Guzman, William H. Robinson, Charles L. White, Paul Henson, Ding Chen, Lauren J. Lahey, Nancy L. Monson, Edgar Meinl, Min Li, E. Sally Ward, Ann J. Ligocki, Benjamin Greenberg, William Rounds, Donna Graves, Elliot M. Frohman, Jacqueline R. Rivas, Ann M. Stowe |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Autoimmunity Neurodegenerative Relapsing-Remitting medicine.disease_cause multiple sclerosis Transgenic Mice Medicine 2.1 Biological and endogenous factors Gray Matter Encephalomyelitis B cell B-Lymphocytes biology General Neuroscience Brain Middle Aged Recombinant Proteins Stroke Oligodendroglia medicine.anatomical_structure Neurological Immunohistochemistry Original Article Female Antibody Biotechnology Adult Multiple Sclerosis Encephalomyelitis Autoimmune Experimental Mice Transgenic Autoimmune Disease lcsh:RC321-571 Experimental Young Adult Multiple Sclerosis Relapsing-Remitting Antigen Clinical Research Animals Humans lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Autoantibodies Glycoproteins Neuromyelitis optica business.industry Multiple sclerosis Autoantibody Neurosciences myelin tracts medicine.disease Brain Disorders Hela Cells clinically isolated syndrome Immunology biology.protein Neurology (clinical) business autoantibody Autoimmune HeLa Cells |
| Zdroj: | ASN NEURO ASN neuro, vol 7, iss 5 ASN Neuro, Vol 7 (2015) |
| ISSN: | 1759-0914 |
| Popis: | * These authors contributed equally to the work in this manuscript. We have previously identified a distinct class of antibodies expressed by B cells in the cerebrospinal fluid (CSF) of early and established relapsing remitting multiple sclerosis (RRMS) patients that is not observed in healthy donors. These antibodies contain a unique pattern of mutations in six codons along VH4 antibody genes that we termed the antibody gene signature (AGS). In fact, patients who have such B cells in their CSF are identified as either having RRMS or developing RRMS in the future. As mutations in antibody genes increase antibody affinity for particular antigens, the goal for this study was to investigate whether AGS+ antibodies bind to brain tissue antigens. Single B cells were isolated from the CSF of 10 patients with early or established RRMS. We chose 32 of these B cells that expressed antibodies enriched for the AGS for further study. We generated monoclonal full-length recombinant human antibodies (rhAbs) and used both immunological assays and immunohistochemistry to investigate the capacity of these AGS+ rhAbs to bind brain tissue antigens. AGS+ rhAbs did not recognize myelin tracts in the corpus callosum. Instead, AGS+ rhAbs recognized neuronal nuclei and/or astrocytes, which are prevalent in the cortical gray matter. This pattern was unique to the AGS+ antibodies from early and established RRMS patients, as AGS+ antibodies from an early neuromyelitis optica patient did not display the same reactivity. Prevalence of CSF-derived B cells expressing AGS+ antibodies that bind to these cell types may be an indicator of gray matter-directed autoimmunity in early and established RRMS patients. |
| Databáze: | OpenAIRE |
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