Journal article
Generation of human monoclonal autoantibodies from rare myelin oligodendrocyte glycoprotein-specific patient-derived B cells using an optofluidic-based platform
- Abstract:
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Background: Monoclonal antibodies (mAbs) are powerful tools for elucidating disease mechanisms. Capturing heterogeneity of patient responses—including clonality, somatic mutations, isotypes, and pathogenic potential—requires building large libraries of mAbs using high-throughput approaches. However, current techniques for identifying and isolating patient-derived mAbs targeting conformational epitopes on membrane proteins remain labor-intensive and inefficient.
Objective: Evaluate a high-throughput antibody discovery pipeline to generate patient B cell-derived mAbs against myelin oligodendrocyte glycoprotein (MOG), a transmembrane autoantigen targeted in MOG antibody-associated disease (MOGAD).
Methods: An optofluidic-based workflow incorporated mammalian display of human MOG (hMOG) in a live cell-based assay (CBA) format. B-cell receptor sequences from individual hMOG-binding B cells were cloned and expressed to generate mAbs from three patients. The hMOG binding specificity of these mAbs was validated in off-platform hMOG-CBAs.
Results: Validated hMOG-specific antibody-secreting cells in one patient represented 0.02% of all single B cells screened. From these low-frequency populations, one patient-B-cell-derived IgG mAb was successfully generated and validated. This human IgG mAb, characterized by a high frequency of Vregion somatic mutations (5-12.2%), bound hMOG at concentrations as low as 1 ng/mL.
Discussion: This workflow enables rapid discovery of rare, patient-derived mAbs targeting conformational epitopes on membrane antigens, offering a scalable approach for dissecting autoantibody repertoires.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 636.9KB, Terms of use)
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- Publisher copy:
- 10.1212/NXI.0000000000200577
Authors
- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 104079/Z/14/Z
- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- MR/V007173/1
- Publisher:
- Lippincott, Williams & Wilkins
- Journal:
- Neurology, Neuroimmunology and Neuroinflammation More from this journal
- Volume:
- 13
- Issue:
- 3
- Article number:
- e200577
- Publication date:
- 2026-04-29
- Acceptance date:
- 2026-02-12
- DOI:
- EISSN:
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2332-7812
- Language:
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English
- Keywords:
- Pubs id:
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2370122
- Local pid:
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pubs:2370122
- Deposit date:
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2026-02-11
- ARK identifier:
Terms of use
- Copyright holder:
- Panicker et al.
- Copyright date:
- 2026
- Rights statement:
- Copyright © 2026 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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