Skip to main content
SpringerLink
Log in

Correlation between severe attacks and serum aquaporin-4 antibody titer in neuromyelitis optica spectrum disorder

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Aquaporin 4-immunoglobulin G (AQP4-IgG) specifically targets aquaporin 4 in approximately 80% of Neuromyelitis Optica Spectrum Disorder (NMOSD) cases. NMOSD is presently categorized as anti-AQP4-antibody (Ab) positive or negative based on AQP4-Ab presence. The association between antibody titers and patient prognosis remains unclear. Therefore, the present study explores the correlation between severe attacks and serum AQP4 Ab titers in patients with neuromyelitis optica spectrum disorder. Data were gathered retrospectively from 546 patients with NMOSD between September 1, 2009, and December 1, 2021. Patients were categorized based on their AQP4-Ab titers: AQP4 titer ≥ 1:320 were classified as the high-titer group, AQP4 (+ +), and AQP4 titer of ≤ 1:100 were classified as the low-titer group, AQP4 ( +). Clinical characteristics and prognoses between the two groups were compared. Patients with AQP4 ( +) exhibited few severe optic neuritis (SON) attacks (false discovery rate [FDR] corrected p < 0.001), a reduced percentage experiencing SON attacks, and a lower incidence of visual disability than patients with AQP4 (+ +). Patients with AQP4 (+ +) and AQP4 ( +) NMOSD exhibited significant difference in annual recurrence rate (ARR) (FDR-corrected p < 0.001). The lower AQP4 Ab titer group demonstrated reduced susceptibility to severe relapse with conventional immunosuppressive agents and rituximab (RTX) than the higher titer group. No significant differences in sex, age at onset, coexisting connective tissue diseases, motor disability, or mortality rates were observed between the two groups. Higher AQP4 Ab titers correlated with increased disease severity and visual disability in patients with NMOSD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

Anonymized data not published within this article will be made available on request from any appropriately qualified investigator.

References

  1. Wingerchuk DM, Banwell B, Bennett JL et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85(2):e177–e189. https://doi.org/10.1212/WNL.0000000000001729

    Article  Google Scholar 

  2. Jiao Y, Fryer JP, Lennon VA et al (2013) Updated estimate of AQP4-IgG serostatus and disability outcome in neuromyelitis optica. Neurology 81(14):e1197–e1204. https://doi.org/10.1212/WNL.0b013e3182a6cb5c

    Article  CAS  Google Scholar 

  3. Misu T, Fujihara K, Kakita A et al (2007) Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis. Brain 130(5):1224–1234. https://doi.org/10.1093/brain/awm047

    Article  CAS  PubMed  Google Scholar 

  4. Roemer SF, Parisi JE, Lennon VA et al (2007) Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis. Brain 130(5):1194–1205. https://doi.org/10.1093/brain/awl371

    Article  PubMed  Google Scholar 

  5. Ma X, Kermode AG, Hu X et al (2020) NMOSD acute attacks: understanding, treatment, and innovative treatment prospects. J Neuroimmunol 348:577387. https://doi.org/10.1016/j.jneuroim.2020.577387

    Article  CAS  PubMed  Google Scholar 

  6. Bonnan M, Valentino R, Debeugny S et al (2018) Short delay into initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders. J Neurosurg Psychiatry 89(4):346–351. https://doi.org/10.1136/jnnp-2017-316286

    Article  Google Scholar 

  7. Jarius S, Ruprecht K, Wildemann B et al (2012) Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation 9:14. https://doi.org/10.1186/1742-2094-9-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Du Q, Shi Z, Chen H et al (2021) Comparison of clinical characteristics and prognoses in patients with different AQP4-Ab and MOG-Ab serostatuses with neuromyelitis optica spectrum disorders. J Neuroimmunol 353:577494. https://doi.org/10.1016/j.jneuroim.2021.577494

    Article  CAS  PubMed  Google Scholar 

  9. Jarius S, Aboul-Enein F, Waters P et al (2008) Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain 131(11):3072–3080. https://doi.org/10.1093/brain/awn240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Takahashi T, Fujihara K, Nakashima I et al (2007) Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 130(5):1235–1243. https://doi.org/10.1093/brain/awm062

    Article  PubMed  Google Scholar 

  11. Li M, Su W, Wang J et al (2013) Detection of anti-aquaporin-4 autoantibodies in the sera of Chinese neuromyelitis optica patients. Neural Regen Res 8(8):708–713. https://doi.org/10.3969/j.issn.1673-5374.2013.08.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Huang X, Xu FF, Qian HR et al (2018) Clinical presentations of neuromyelitis optica spectrum disorders with ultra-longitudinally extensive transverse myelitis. Eur PMC 98(21):1658–1663. https://doi.org/10.3760/cma.j.issn.0376-2491.2018.21.008

    Article  CAS  Google Scholar 

  13. Akaishi T, Takahashi T, Himori N et al (2020) Serum AQP4-IgG level is associated with the phenotype of the first attack in neuromyelitis optica spectrum disorders. J Neuroimmunol 340:577168. https://doi.org/10.1016/j.jneuroim.2020.577168

    Article  CAS  PubMed  Google Scholar 

  14. Akaishi T, Takahashi T, Nakashima I et al (2020) Repeated follow-up of AQP4-IgG titer by cell-based assay in neuromyelitis optica spectrum disorders (NMOSD). J Neurol Sci 410:116671. https://doi.org/10.1016/j.jns.2020.116671

    Article  CAS  PubMed  Google Scholar 

  15. Kessler RA, Mealy MA, Jimenez-Arango JA et al (2017) Anti-aquaporin-4 titer is not predictive of disease course in neuromyelitis optica spectrum disorder: a multicenter cohort study. Multi Scler Relat Disorder 17:198–201. https://doi.org/10.1016/j.msard.2017.08.005

    Article  Google Scholar 

  16. Schmetzer O, Lakin E, Roediger B et al (2021) Anti-aquaporin 4 IgG is not associated with any clinical disease characteristics in neuromyelitis optica spectrum disorder. Front Neurol 12:635419. https://doi.org/10.3389/fneur.2021.635419

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wingerchuk DM, Lennon VA, Pittock SJ et al (2006) Revised diagnostic criteria for neuromyelitis optica. Neurology 66(10):1485–1489. https://doi.org/10.1212/01.wnl.0000216139.44259.74

    Article  CAS  PubMed  Google Scholar 

  18. Jarius S, Probst C, Borowski K et al (2010) A standardized method for detecting antibodies against aquaporin-4 is based on a highly sensitive immunofluorescence assay employing a recombinant target antigen. J Neurol Sci 291:52–56. https://doi.org/10.1016/j.jns.2010.01.002

    Article  CAS  PubMed  Google Scholar 

  19. Yin HX, Wang YJ, Liu MG et al (2023) Aquaporin-4 antibody dynamics and relapse risk in seropositive neuromyelitis optica spectrum disorder treated with immunosuppressants. Ann Neurol 93(6):1069–1081. https://doi.org/10.1002/ana.26623

    Article  CAS  PubMed  Google Scholar 

  20. Chen H, Qiu W, Zhang Q et al (2016) Comparison of the efficacy and tolerability of mycophenolate mofetil and azathioprine as treatments for neuromyelitis optica and neuromyelitis optica spectrum disorder. Eur J Neurol 24(1):219–226. https://doi.org/10.1111/ene.13186

    Article  PubMed  Google Scholar 

  21. Wang R, Sun DR, Du Q et al (2023) Serum antinuclear antibodies associate with severe disease activity in neuromyelitis optica spectrum disorder. J Neuroimmunol 382:578151. https://doi.org/10.1016/j.jneuroim.2023.578151

    Article  CAS  PubMed  Google Scholar 

  22. Yang Y, Huang DH, Wu WP et al (2013) The role of aquaporin-4 antibodies in Chinese patients with neuromyelitis optica. J Clin Neurosci 20(1):94–98. https://doi.org/10.1016/j.jocn.2012.06.006

    Article  CAS  PubMed  Google Scholar 

  23. Palace J, Lin DY, Zeng D et al (2019) Outcome prediction models in AQP4-IgG positive neuromyelitis optica spectrum disorders. Brain 142(5):1310–1323. https://doi.org/10.1093/brain/awz054

    Article  PubMed  PubMed Central  Google Scholar 

  24. Luo W, Kong L, Chen H et al (2023) Visual disability in neuromyelitis optica spectrum disorders: prognostic prediction models. Front Immunol 2023(14):1209323. https://doi.org/10.3389/fimmu.2023.1209323

    Article  CAS  Google Scholar 

  25. Liu J, Tan G, Li B et al (2021) Serum Aquaporin 4-immunoglobulin G titer and neuromyelitis optica spectrum disorder activity and severity: a systematic review and meta-analysis. Front Neurol 12:746959. https://doi.org/10.3389/fneur.2021.746959

    Article  PubMed  PubMed Central  Google Scholar 

  26. Isobe N, Yonekawa T, Matsushita T et al (2012) Quantitative assays for anti-aquaporin-4 antibody with subclass analysis in neuromyelitis optica. Mult Scler (Houndmills, Basingstoke, England) 18(11):1541–1551. https://doi.org/10.1177/1352458512443917

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded by Department of Science and Technology of Sichuan (2022YFS0315 to HYZ). We are grateful to everyone involved in the study. We would like to thank Editage (www.editage.cn) for English language editing.

Author information

Authors and Affiliations

  1. Department of Neurology, West China Hospital, Sichuan University, No. 37 Guoxue Road, Chengdu, Sichuan, People’s Republic of China

    Rui Wang, Dongren Sun, Xiaofei Wang, Ziyan Shi, Lingyao Kong, Qin Du, Ying Zhang, Hongxi Chen, Wenqin Luo, Nana Zhang & Hongyu Zhou

Authors
  1. Rui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dongren Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaofei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ziyan Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lingyao Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qin Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hongxi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wenqin Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nana Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hongyu Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RW and HYZ conceived the idea of the study; DRS and XFW analysed the data; ZYS, LYK, QD, HXC, YZ, WQL, NNZ contributed data acquisition; ZYS and HXC interpreted the results; RW and HYZ wrote the paper; all authors discussed the results and revised the manuscript.

Corresponding author

Correspondence to Hongyu Zhou.

Ethics declarations

Conflicts of interest

None of the authors have any conflicts of interest to declare.

Ethical approval

This study was approved by the Medical Ethics Committee of the West China Hospital, Sichuan University. Patients provided written informed consent to participate in this study.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, R., Sun, D., Wang, X. et al. Correlation between severe attacks and serum aquaporin-4 antibody titer in neuromyelitis optica spectrum disorder. J Neurol (2024). https://doi.org/10.1007/s00415-024-12382-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00415-024-12382-5

Keywords

Search

Navigation