Recombinant antibodies derived from laser captured single plasma cells of multiple sclerosis brain identified phage peptides which may be used as tools for characterizing intrathecal IgG response

Kennedy, P. G.E., Graner, M. W., Walker, D., Pointon, T., Fringuello, A. and Yu, X. (2020) Recombinant antibodies derived from laser captured single plasma cells of multiple sclerosis brain identified phage peptides which may be used as tools for characterizing intrathecal IgG response. Journal of Neuroimmunology, 347, 577319. (doi: 10.1016/j.jneuroim.2020.577319)

Abstract

Oligoclonal bands and increased IgG antibody levels can be detected in the cerebrospinal fluid in vast majority of patients with Multiple Sclerosis (MS). However, the antigenic specificity of oligoclonal IgG has yet to be determined. Using laser capture microdissection, we isolated single CD38+ plasma cells from lesion areas in two autopsy MS brains, and generated three recombinant antibodies (rAbs) from clonally expanded plasma cells. Panning phage-displayed random peptide libraries was carried out to determine peptide antigen specificities of these MS brain rAbs. We identified 25 high affinity phage peptides from which 5 peptides are unique. Database searches revealed that they shared sequence homologies with Epstein-Barr nuclear antigens 4 and 6, as well as with other viral proteins. Significantly, these peptides were recognized by intrathecal IgG and oligoclonal IgG bands in other MS patients. Our results demonstrate that functional recombinant antibodies can be generated from clonally expanded plasma cells in MS brain lesions by laser capture microdissection, and that these MS brain rAbs have the potential for determining the targets of intrathecal IgG and oligoclonal bands.

• Item Type: Articles
• Additional Information: This work was supported in part by Centre for Neuroscience, University of Colorado Anschutz Medical Campus, and a Pilot Research Award (PP1662) for Dr. Yu from National Multiple Sclerosis Society. The University of Colorado Genomics and Microarray Shared Resource is sponsored by Cancer Centre Support Grant (P30CA046934). Drs. Yu and Graner are supported by 5R21MH118174-02 from the NIH/NIMH.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kennedy, Professor Peter
• Authors: Kennedy, P. G.E., Graner, M. W., Walker, D., Pointon, T., Fringuello, A., and Yu, X.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Neuroimmunology
• Publisher: Elsevier
• ISSN: 0165-5728
• ISSN (Online): 1872-8421
• Published Online: 14 July 2020
• Copyright Holders: Copyright © 2020 Elsevier B.V.
• First Published: First published in Journal of Neuroimmunology 347: 577319
• Publisher Policy: Reproduced in accordance with the publisher copyright policy