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FCGR3A Polymorphism Controls B-Cell Repopulation Kinetics in People With Multiple Sclerosis Treated With Ocrelizumab
Gianmarco Abbadessa1,2, Ugo Chianese3, Claudia Russo4
1Dipartimento di Scienze Mediche e Chirurgiche Avanzate, Università della Campania Luigi Vanvitelli, Napoli, Italia.
Neurology(R) Neuroimmunology & Neuroinflammation
|August 11, 2026
Summary
The FCGR3A V158F polymorphism influences ocrelizumab (OCR) efficacy in multiple sclerosis (MS) by affecting B-cell repopulation. Longer infusion intervals increase B-cell repopulation, particularly in FCGR3A-F allele carriers.
Area of Science:
- Immunogenetics
- Neuroimmunology
- Pharmacogenomics
Background:
- Fc gamma receptor 3A (FCGR3A) V158F polymorphism impacts anti-CD20 therapy response in autoimmune diseases.
- Ocrelizumab (OCR) is an anti-CD20 therapy for multiple sclerosis (MS), but the role of FCGR3A V158F polymorphism in its efficacy is unclear.
- This study investigates the influence of FCGR3A V158F polymorphism on B-cell repopulation and disease activity in MS patients treated with OCR.
Purpose of the Study:
- To determine if FCGR3A V158F polymorphism affects B-cell repopulation and disease activity in MS patients receiving OCR.
- To assess genotype-dependent differences in OCR binding to FcγRIIIa-expressing natural killer (NK) cells.
Main Methods:
- Observational cohort study of 101 MS patients treated with OCR.
- FCGR3A V158F genotyping via pyrosequencing.
- Primary outcome: preinfusion CD19+ B-cell repopulation; Secondary outcomes: clinical and MRI inflammatory activity; Ex vivo substudy: OCR/rituximab binding to NK cells.
Main Results:
- Longer OCR infusion intervals were associated with increased odds of B-cell repopulation (OR per +30 days, 2.02).
- FCGR3A F-carrier status significantly modified interval length effect on B-cell repopulation (interaction OR, 2.47).
- FCGR3A genotype did not correlate with clinical or MRI activity; however, FCGR3A-FF donors showed lower OCR/rituximab binding to NK cells.
Conclusions:
- Longer OCR infusion intervals increase B-cell repopulation, with the FCGR3A V158F polymorphism modulating this effect.
- Reduced OCR binding to NK cells in FCGR3A-F allele carriers may explain altered B-cell repopulation kinetics.
- Prospective studies are needed to optimize OCR dosing intervals based on FCGR3A V158F genotype and B-cell repletion.
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