| Title: |
Lymphocyte alterations and elevated complement signaling are key features of refractory myasthenia gravis |
| Authors: |
Dodd KC; Baillie K; Holt JKL; Leite MI; Lin L; West PW; Miller JAL; Spillane J; Viegas S; Zelek WM; Sussman J; Menon M |
| Source: |
Med, 2026 |
| Publisher Information: |
Cell Press |
| Publication Year: |
2026 |
| Collection: |
Newcastle University Library ePrints Service |
| Description: |
© 2025 The Authors. Background: A significant proportion of patients with myasthenia gravis (MG) remain refractory to standard immunosuppressive therapy, and biomarkers to help guide treatment decisions are lacking. We investigated whether refractory disease is associated with a distinct circulating immune profile. Methods: We performed comprehensive immune phenotyping of peripheral blood from patients with acetylcholine-receptor-antibody-positive MG with differing treatment requirements and compared them with healthy controls. In a subset of refractory patients treated with anti-CD20 therapy, B cell reconstitution and clinical response were evaluated. Findings: Refractory MG patients displayed the highest frequency of memory B cells and increased production of interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) upon Toll-like receptor/CD40 activation in vitro. These changes were accompanied by a dramatic loss of regulatory T cells (Tregs) and dendritic cells. Refractory MG was further characterized by elevated circulating complement proteins (C3, C5, and clusterin) and increased expression of complement receptors on lymphocytes. Following anti-CD20 therapy, residual plasmablasts persisted in circulation. Notably, a low baseline B cell frequency ( |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://eprints.ncl.ac.uk/310586; https://eprints.ncl.ac.uk/fulltext.aspx?url=310586/21A6F2A0-98FA-42BB-A290-6C0DD53A7EAF.pdf&pub_id=310586 |
| Availability: |
https://eprints.ncl.ac.uk/310586 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.8837F9A6 |
| Database: |
BASE |