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| Item Type: | Article |
|---|---|
| Title: | HLA associations differ by ethnicity and aquaporin-4 antibody status in patients with neuromyelitis optica spectrum disorders |
| Creators Name: | Niederschweiberer, Moritz, Panagiotaropoulou, Georgia, Fernandez-Viña, Marcelo A., Montero-Martin, Gonzalo, Osoegawa, Kazutoyo, Behne, Megan, Franke, Andre, Lieb, Wolfgang, Jarius, Sven, Wildemann, Brigitte, Schindler, Patrick, Otto, Carolin, Paul, Friedemann, Flanagan, Eoin P., Cook, Lawrence J., Oksenberg, Jorge, Yeaman, Michael R., Ripke, Stephan and Ruprecht, Klemens |
| 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 AQP4IgG 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: In White AQP4-IgG+ patients with NMOSD, the most significantly associated alleles were HLA-DQA1*05:01:01 (30.1% vs 11.1%, odds ratio 3.43 [95% CI 2.65–4.42], corrected p = 8.95E-17), HLA-DQB1*02:01:01 (29.9% vs 11.3%, 3.34 [2.58–4.31], corrected p = 4.33E-16), and HLA-DRB1*03:01:01 (29.2% vs 11.6%, 3.15 [2.43–4.06], corrected p = 3.66E-14), followed by HLA-B*08:01:01 (26% vs 10.4%, 3.02 [2.3–3.94] corrected p = 8.79E-12), HLAC*07:01:01 (27.8% vs 14%, 2.36 [1.81–3.04], corrected p = 2.44E-07), and HLA-DRB3*01:01: 02 (28% vs 14.7%, 2.27 [1.73–2.95], corrected p = 2.19E-06). The frequency of HLA-DRB1*08: 04:01 was higher in Black AQP4-IgG+ patients with NMOSD than in Black controls but did not achieve statistical significance (19.3% vs 5.7%, 3.92 [1.91–7.86], corrected p = 0.08). Nevertheless, when compared with a larger cohort of Black controls (n = 16,178), the frequency of HLA-DRB1*08:04 (19.3% vs 5.1%, 4.46 [2.45–7.66], corrected p = 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. DISCUCCION: This study confirms the previously recognized association of HLA-DRB1*03:01 with AQP4-IgG+ NMOSD in White patients and extends this association to the HLA-DRB1*03:01:01;HLA-DQA1*05:01:01;HLA-DQB1*02:01:01 haplotype. Furthermore, it identifies an association of HLA-DRB1*08:04 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. |
| Keywords: | Aquaporin 4, Autoantibodies, Hispanic or Latino, Immunoglobulin G, Neuromyelitis Optica, White People |
| Source: | Neurology Neuroimmunology & Neuroinflammation |
| ISSN: | 2332-7812 |
| Publisher: | Wolters Kluwer / American Academy of Neurology |
| Volume: | 13 |
| Number: | 3 |
| Page Range: | e200562 |
| Date: | May 2026 |
| Official Publication: | https://doi.org/10.1212/nxi.0000000000200562 |
| PubMed: | View item in PubMed |
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