HLA Associations Differ by Ethnicity and Aquaporin-4 Antibody Status in Patients With Neuromyelitis Optica Spectrum Disorders

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorders (NMOSDs) comprise inflammatory processes of the CNS. Most patients with NMOSD have serum immunoglobulin (Ig) G autoantibodies directed against the astrocytic water channel aquaporin-4 (AQP4-IgG). In this study, we analyzed HLA allelic frequencies in a large cohort of patients with NMOSD, stratified by ethnicity and AQP4-IgG status, compared with healthy controls. METHODS: Next-generation sequencing-based HLA class I and II genotyping was performed in 174 White, 45 Black, and 41 Hispanic AQP4-IgG-positive (AQP4-IgG+) patients with NMOSD; 49 White patients with AQP4-IgG-negative (AQP4-IgG-) NMOSD; and 2,427 White, 244 Black, and 155 Hispanic controls. Correction for multiple testing was performed using the Bonferroni method. RESULTS: = 1.88E-03) was significantly higher in Black AQP4-IgG+ patients with NMOSD. No significant HLA associations were detected in AQP4-IgG+ Hispanic patients or White AQP4-IgG- patients with NMOSD. DISCUSSION: with AQP4-IgG+ NMOSD in Black patients. However, no HLA associations were detected in White AQP4-IgG- patients with NMOSD. The immunogenetic differences between AQP4-IgG+ and AQP4-IgG- NMOSD support pathophysiologic distinctions between these entities.

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Journal
Neurology Neuroimmunology & Neuroinflammation
Published
2026-04-16
DOI
https://doi.org/10.1212/nxi.0000000000200562
Primary Topic
Multiple Sclerosis Research Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

HLA Associations Differ by Ethnicity and Aquaporin-4 Antibody Status in Patients With Neuromyelitis Optica Spectrum Disorders

Jacinta M. Behne, Sarah M. Planchon, Georgia Panagiotaropoulou, Pavle Repovic et al.
Neurology Neuroimmunology & Neuroinflammation
Multiple Sclerosis Research Studies
article

HLA Associations Differ by Ethnicity and Aquaporin-4 Antibody Status in Patients With Neuromyelitis Optica Spectrum Disorders

Jacinta M. Behne, Sarah M. Planchon, Georgia Panagiotaropoulou, Pavle Repovic, Brigitte Wildemann, Wolfgang Lieb, Marcelo Fernández-Viña, Jeffrey L. Bennett, Michael R. Yeaman, Anthony Traboulsee, Eoin P. Flanagan, Patrick Schindler, Stephan Ripke, Klemens Ruprecht, Gonzalo Montero-Martín, Lawrence J. Cook, Ilya Kister, Kazutoyo Osoegawa, Carolin Otto, André Franke, Terry J. Smith, Sven Jarius, Jorge R. Oksenberg, Moritz Niederschweiberer, Michael Levy, Claire S. Riley, Megan Behne, Friedemann Paul, May H. Han
article en

Abstract

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorders (NMOSDs) comprise inflammatory processes of the CNS. Most patients with NMOSD have serum immunoglobulin (Ig) G autoantibodies directed against the astrocytic water channel aquaporin-4 (AQP4-IgG). In this study, we analyzed HLA allelic frequencies in a large cohort of patients with NMOSD, stratified by ethnicity and AQP4-IgG status, compared with healthy controls. METHODS: Next-generation sequencing-based HLA class I and II genotyping was performed in 174 White, 45 Black, and 41 Hispanic AQP4-IgG-positive (AQP4-IgG+) patients with NMOSD; 49 White patients with AQP4-IgG-negative (AQP4-IgG-) NMOSD; and 2,427 White, 244 Black, and 155 Hispanic controls. Correction for multiple testing was performed using the Bonferroni method. RESULTS: = 1.88E-03) was significantly higher in Black AQP4-IgG+ patients with NMOSD. No significant HLA associations were detected in AQP4-IgG+ Hispanic patients or White AQP4-IgG- patients with NMOSD. DISCUSSION: with AQP4-IgG+ NMOSD in Black patients. However, no HLA associations were detected in White AQP4-IgG- patients with NMOSD. The immunogenetic differences between AQP4-IgG+ and AQP4-IgG- NMOSD support pathophysiologic distinctions between these entities.

Neurology Neuroimmunology & NeuroinflammationVol. 13(3)
Broad Institute (US), Mayo Clinic (US), University of California, Los Angeles (US), University of California, San Francisco (US), Max Delbrück Center (DE), University of Utah (US), Heidelberg University (DE), UCLA Medical Center (US), Christian-Albrechts-Universität zu Kiel (DE), Humboldt-Universität zu Berlin (DE), Massachusetts General Hospital (US), Guthy-Jackson Charitable Foundation (US), Mayo Clinic in Arizona (US), Vitalant (US), Stanford Blood Center (US), Institute of Neuroimmunology of the Slovak Academy of Sciences (SK), University of Utah Health Care (US), Harbor–UCLA Medical Center (US), Stanford University (US)
U.S. Department of Defense, Guthy-Jackson Charitable Foundation, Arthur Arnstein Stiftung, Multiple Sclerosis Society, European Commission, Deutsche Forschungsgemeinschaft, Stiftung Charité, National Institutes of Health, University of California, San Francisco
Openalex Percentile: Top 25%
Multiple Sclerosis Research Studies
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