Cellular changes in eculizumab early responders with generalized myasthenia gravis.
Journal Article (Journal Article)
Eculizumab (ECU), a C5 complement inhibitor, is approved to treat acetylcholine receptor autoantibody positive generalized myasthenia gravis (AChR MG). The clinical effect of ECU relies on inhibition of the terminal complement complex; however, the effect of ECU on lymphocytes is largely unknown. We evaluated innate and adaptive immunity among AChR MG patients (N = 3) before ECU and ≥3 months later while on stable therapy, and found reduced activation markers in memory CD4+ T cell subsets, increased regulatory T cell populations, and reduced frequencies of CXCR5+HLA-DR+CCR7+ Tfh subsets and CD11b+ migratory memory B cells. We observed increases within CD8+ T cell subsets that were terminally differentiated and senescent. Our data suggest complement inhibition with ECU modulates the adaptive immunity in patients with MG, consistent with preclinical data showing changes in complement-mediated signaling by T- and antigen-presenting cells. These findings extend our understanding of ECU's mechanism of action when treating patients with MG.
Full Text
Duke Authors
Cited Authors
- Li, Y; Yi, JS; Howard, JF; Chopra, M; Russo, MA; Guptill, JT
Published Date
- October 2021
Published In
Volume / Issue
- 231 /
Start / End Page
- 108830 -
PubMed ID
- 34450290
Electronic International Standard Serial Number (EISSN)
- 1521-7035
Digital Object Identifier (DOI)
- 10.1016/j.clim.2021.108830
Language
- eng
Conference Location
- United States