B cell and aquaporin-4 antibody relationships with neuromyelitis optica spectrum disorder activity.

1. Ann Clin Transl Neurol. 2024 Oct;11(10):2792-2798. doi: 10.1002/acn3.52171. Epub 2024 Sep 2.

B cell and aquaporin-4 antibody relationships with neuromyelitis optica spectrum disorder activity.

Bennett JL(1), Pittock SJ(2), Paul F(3), Kim HJ(4), Irani SR(5)(6), O’Connor KC(7), Patterson KR(8), Smith MA(8), Gunsior M(8), Mittereder N(8), Rees WA(8), Cimbora D(8), Cree BAC(9).

Author information: (1)Departments of Neurology and Ophthalmology, Programs in Neuroscience and Immunology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA. (2)Neurology, Laboratory Medicine and Pathology, Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota, USA. (3)Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin, Berlin, Germany. (4)Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, Republic of Korea. (5)Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. (6)Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA. (7)Department of Neurology and Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA. (8)Horizon Therapeutics (now Amgen Inc., Thousand Oaks, California, USA), Gaithersburg, Maryland, USA. (9)UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, USA.

This post hoc analysis of the randomized, placebo-controlled N-MOmentum study (NCT02200770) of inebilizumab in neuromyelitis optica spectrum disorder (NMOSD) evaluated relationships between circulating B-cell subsets and aquaporin-4 immunoglobulin G (AQP4-lgG) titers and attacks. Among participants receiving placebo, CD20+ and CD27+ B-cell counts were modestly increased from the pre-attack visit to attack; plasmablast/plasma cell gene signature was increased from baseline to the pre-attack visit (p = 0.016) and from baseline to attack (p = 0.009). With inebilizumab treatment, B-cell subset counts decreased and did not increase with attacks. No difference in change of AQP4-IgG titers from baseline to time of attack was observed.

© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

DOI: 10.1002/acn3.52171 PMCID: PMC11514900 PMID: 39222408 [Indexed for MEDLINE]

Conflict of interest statement: JLB has received study design/consultation fees from MedImmune/Viela Bio (now Amgen) and personal fees from AbbVie, Alexion, Antigenomycs, BeiGene, Chugai, Clene Nanomedicine, EMD Serono, Genentech, Genzyme, Mitsubishi Tanabe Pharma, Novartis, Reistone Bio, Roche, Imcyse, and TG Therapeutics. He has received grants from the National Institutes of Health, Novartis, and Mallinckrodt, and holds a patent for Aquaporumab. SJP has received grants, personal fees, and nonfinancial support from Alexion; grants from Autoimmune Encephalitis Alliance; grants, personal fees, nonfinancial support, and other support from MedImmune and Viela Bio (now Amgen); grants, personal fees, nonfinancial support, and other support from Roche, Genentech; consulting support from Astellas; and personal fees for consulting services from UCB. He holds the following patents that are relevant to this work: Patent #8889102 (Application #12‐678350, Neuromyelitis Optica Autoantibodies as a Marker for Neoplasia) and Patent #9891219B2 (Application #12‐573942, Methods for Treating Neuromyelitis Optica [NMO] by Administration of Eculizumab to an Individual that is Aquaporin‐4[AQP4]‐IgG Autoantibody Positive) for which he has received royalties. He works as a consultant in the Mayo Clinic Neuroimmunology Laboratory clinical service. The Mayo Clinic Neuroimmunology Laboratory commercially offers AQP4‐IgG testing, but revenue accrued does not contribute to salary, research support, or personal income. FP has received research support, speaker fees, and travel reimbursement from Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, and Teva. He is supported by the German Competence Network for Multiple Sclerosis and the German Research Council (DFG Exc 257). He has received travel reimbursement from the Guthy–Jackson Charitable Foundation and serves on the steering committee of the OCTIMS study sponsored by Novartis. HJK received a grant from the National Research Foundation of Korea and research support from Aprilbio, Eisai, and UCB, and has received consultancy/speaker fees from Alexion, Altos Biologics, AstraZeneca, Biogen, Daewoong Pharmaceutical, Eisai, GC Pharma, Handok Pharmaceutical, Kaigene, Kolon Life Science, MDimune, Merck Serono, Mitsubishi Tanabe Pharma, Roche, and Sanofi Genzyme. He is a coeditor for the Multiple Sclerosis Journal and an associated editor for the Journal of Clinical Neurology. SRI has recei