FCRL3 genetic variants drive autoimmune pathogenesis in multiple sclerosis and neuromyelitis optica spectrum disorders

Hui-Fen Huang, Qi-Bing Liu, Yong-Feng Xu, Gui-Xian Zhao, Haipeng Liu, Hao Yu, Zhi-Ying Wu

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Abstract

Objective: This study aims to investigate the association of Fc receptor-like 3 (FCRL3) gene variants with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) in a Chinese population cohort.
Methods: In Stage 1, 154 MS patients, 109 NMOSD patients, and 301 normal controls were recruited, Sequenom MassARRAY technology was used for genotyping single nucleotide polymorphisms (SNPs). Stage 2 involved an independent cohort of 95 MS patients, 139 NMOSD patients, and 226 normal controls. Two FCRL3 SNPs (rs7528684 and rs11264799) were determined using allele-specific polymerase chain reaction (PCR) with specific primers.
Results: Allele C of rs7528684 emerged as a protective factor for MS. Allele A of rs11264799 exhibited no significant effect on MS or NMOSD. A notable disparity in rs7528684 genotype distribution was observed between oligoclonal band (OCB)-positive and OCB-negative MS patients. Allele C of rs7528684 exhibited an association with OCB-positive MS patients.
Conclusion: The findings suggest that the FCRL3 variant (rs7528684) is associated with MS rather than NMOSD. FCRL3 might significantly contribute to OCB synthesis, while the underlying mechanisms warrant further elucidation.
Original languageEnglish
Article number1552149
Number of pages9
JournalFrontiers in Neurology
Volume16
DOIs
Publication statusPublished - 4 Jul 2025

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Funding

The author(s) declare that financial support was received for the research and/or publication of this article. This study was supported by the research foundation for distinguished scholar of Zhejiang University to Zhi-Ying Wu (188020\u2013193810101/089) and the National Natural Science Foundation of China (82201513).

FundersFunder number
Zhejiang University188020–193810101/089
Zhejiang University
National Natural Science Foundation of China82201513
National Natural Science Foundation of China

    Keywords

    • multiple sclerosis
    • neuromyelitis optica spectrum disorders
    • FCRL3
    • variant
    • association

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