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Diagnostic value of antibody concentration ratio for treatment-refractory myasthenia gravis

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Abstract

Objective

This study aimed to assess the diagnostic potential of the Antibody concentration ratio in identifying treatment-refractory myasthenia gravis (MG).

Methods

A retrospective analysis was conducted on 116 MG patients who underwent antibody detection at least twice between June 1, 2015, and June 1, 2023. Demographic and clinical characteristics were collated to ascertain their association with refractory MG. The Antibody Concentration Ratio was applied to determine treatment response, using the International Consensus Guidance criteria as the reference standard. The area under nonparametric receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were calculated to assess the diagnostic efficacy of the Antibody concentration ratio following consecutive immunotherapy relative to initial antibody concentrations for refractory MG.

Results

19 out of 116 patients were unequivocally diagnosed with refractory MG. A significant correlation was found between the Antibody Concentration Ratio and refractory MG status in treatment-refractory and treatment-responsive patients. Subsequently, the AUC demonstrated the robust diagnostic capability of the Antibody concentration ratio for refractory MG, with an AUC of 0.8709 (95% CI: 0.7995–0.9422, p < 0.0001). The optimal cut-off value stood at 0.8903, exhibiting a sensitivity of 94.74% (95% CI: 75.36%-99.73%), a specificity of 68.04% (95% CI: 58.23%-76.48%), and accuracy of 72.41% (95% CI: 64.28%-80.54%).

Conclusion

Elevated Antibody Concentration Ratio is intrinsically linked with refractory MG and exhibits potential as an diagnostic biomarker for the condition.

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Data Availability

Data that support the findings of this study is availability. https://figshare.com/. https://doi.org/10.6084/m9.figshare.25287790.

Code availability

Not applicable.

Abbreviations

MG:

Myasthenia gravis

ROC:

Receiver operating characteristic

AChR:

Acetylcholine receptor

MuSK:

Muscle-specific tyrosine kinase

IVIG:

Intravenous immunoglobulin

PLEX:

Plasma exchange

QMGs:

The quantitative myasthenia gravis scores

MG-ADLs:

MG activities of daily living scores

ICG:

International Consensus Guidance

PASS:

Patient-acceptable symptom status

MGFA:

MG Foundation of America

AUC:

Area under the ROC curve

References

  1. Keesey JC (2004) Clinical evaluation and management of myasthenia gravis. Muscle Nerve 29(4):484–505

    Article  PubMed  Google Scholar 

  2. Lindstrom JM, Seybold ME, Lennon VA, Whittingham S, Duane DD (1976) Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology 26(11):1054–9

    Article  CAS  PubMed  Google Scholar 

  3. Evoli A, Alboini PE, Damato V et al (2018) Myasthenia gravis with antibodies to MuSK: an update. Ann N Y Acad Sci 1412(1):82–89

    Article  CAS  PubMed  Google Scholar 

  4. Berrih-Aknin S, Frenkian-Cuvelier M, Eymard B (2014) Diagnostic and clinical classification of autoimmune myasthenia gravis. J Autoimmun 48–49:143–148

    Article  PubMed  Google Scholar 

  5. Cortés-Vicente E, Álvarez-Velasco R, Pla-Junca F et al (2022) Drug-refractory myasthenia gravis: Clinical characteristics, treatments, and outcome. Ann Clin Transl Neurol 9(2):122–131

    Article  PubMed  PubMed Central  Google Scholar 

  6. Dalakas MC (2019) Immunotherapy in myasthenia gravis in the era of biologics. Nat Rev Neurol 15(2):113–124

    Article  PubMed  Google Scholar 

  7. Rath J, Brunner I, Tomschik M et al (2020) Frequency and clinical features of treatment-refractory myasthenia gravis. J Neurol 267(4):1004–1011

    Article  PubMed  Google Scholar 

  8. Mantegazza R, Antozzi C (2018) When myasthenia gravis is deemed refractory: clinical signposts and treatment strategies. Ther Adv Neurol Disord 11:1756285617749134

    Article  PubMed  PubMed Central  Google Scholar 

  9. Veltsista D, Kefalopoulou Z, Tzartos J, Chroni E (2022) Autoantibody profile in myasthenia gravis patients with a refractory phase. Muscle Nerve 65(5):607–611

    Article  CAS  PubMed  Google Scholar 

  10. Kojima Y, Uzawa A, Ozawa Y et al (2021) Rate of change in acetylcholine receptor antibody levels predicts myasthenia gravis outcome. J Neurol Neurosurg Psychiatry 92(9):963–968

    Article  PubMed  Google Scholar 

  11. Jeong S, Noh Y, Oh IS, Hong YH, Shin JY (2021) Survival, Prognosis, and Clinical Feature of Refractory Myasthenia Gravis: a 15-year Nationwide Cohort Study. J Korean Med Sci 36(39):e242

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sanders DB, Burns TM, Cutter GR, Massey JM, Juel VC, Hobson-Webb L (2014) Does change in acetylcholine receptor antibody level correlate with clinical change in myasthenia gravis. Muscle Nerve 49(4):483–486

    Article  CAS  PubMed  Google Scholar 

  13. Oosterhuis HJ, Limburg PC, Hummel-Tappel E, The TH (1983) Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 2. Clinical and serological follow-up of individual patients. J Neurol Sci 58(3):371–85

    Article  CAS  PubMed  Google Scholar 

  14. Heldal AT, Eide GE, Romi F, Owe JF, Gilhus NE (2014) Repeated acetylcholine receptor antibody-concentrations and association to clinical myasthenia gravis development. PLoS ONE 9(12):e114060

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sanders DB, Wolfe GI, Benatar M et al (2016) International consensus guidance for management of myasthenia gravis: Executive summary. Neurology 87(4):419–425

    Article  PubMed  PubMed Central  Google Scholar 

  16. Tran C, Biswas A, Mendoza M, Katzberg H, Bril V, Barnett C (2021) Performance of different criteria for refractory myasthenia gravis. Eur J Neurol 28(4):1375–1384

    Article  PubMed  Google Scholar 

  17. Katzberg HD, Barnett C, Merkies IS, Bril V (2014) Minimal clinically important difference in myasthenia gravis: outcomes from a randomized trial. Muscle Nerve 49(5):661–665

    Article  CAS  PubMed  Google Scholar 

  18. Kanai T, Uzawa A, Kawaguchi N et al (2017) Adequate tacrolimus concentration for myasthenia gravis treatment. Eur J Neurol 24(2):270–275

    Article  CAS  PubMed  Google Scholar 

  19. Mendoza M, Tran C, Bril V, Katzberg HD, Barnett C (2020) Patient-acceptable symptom states in myasthenia gravis. Neurology 95(12):e1617–e1628

    Article  CAS  PubMed  Google Scholar 

  20. Jaretzki A 3rd, Barohn RJ, Ernstoff RM et al (2000) Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 55(1):16–23

    Article  PubMed  Google Scholar 

  21. Schneider-Gold C, Hagenacker T, Melzer N, Ruck T (2019) Understanding the burden of refractory myasthenia gravis. Ther Adv Neurol Disord 12:1756286419832242

    Article  PubMed  PubMed Central  Google Scholar 

  22. Narayanaswami P, Sanders DB, Wolfe G et al (2021) International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update. Neurology 96(3):114–122

    Article  PubMed  PubMed Central  Google Scholar 

  23. Álvarez-Velasco R, Gutiérrez-Gutiérrez G, Trujillo JC et al (2021) Clinical characteristics and outcomes of thymoma-associated myasthenia gravis. Eur J Neurol 28(6):2083–2091

    Article  PubMed  Google Scholar 

  24. Newsom-Davis J, Pinching AJ, Vincent A, Wilson SG (1978) Function of circulating antibody to acetylcholine receptor in myasthenia gravis: investigation by plasma exchange. Neurology 28(3):266–272

    Article  CAS  PubMed  Google Scholar 

  25. Usmani A, Kwan L, Wahib-Khalil D, Trivedi J, Nations S, Sarode R (2019) Excellent response to therapeutic plasma exchange in myasthenia gravis patients irrespective of antibody status. J Clin Apher 34(4):416–422

    Article  PubMed  Google Scholar 

  26. Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren J (2019) Myasthenia gravis Nat Rev Dis Primers 5(1):30

    Article  PubMed  Google Scholar 

  27. Hewer R, Matthews I, Chen S, McGrath V, Evans M, Roberts E et al (2006) A sensitive non-isotopic assay for acetylcholine receptor autoantibodies. Clin Chim Acta 364(1–2):159–166

    Article  CAS  PubMed  Google Scholar 

  28. Schneider-Gold C, Reinacher-Schick A, Ellrichmann G, Gold R (2017) Bortezomib in severe MuSK-antibody positive myasthenia gravis: first clinical experience. Ther Adv Neurol Disord 10(10):339–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hill ME, Shiono H, Newsom-Davis J, Willcox N (2008) The myasthenia gravis thymus: a rare source of human autoantibody-secreting plasma cells for testing potential therapeutics. J Neuroimmunol 201–202:50–56

    Article  PubMed  Google Scholar 

  30. Dalakas MC (2020) Progress in the therapy of myasthenia gravis: getting closer to effective targeted immunotherapies. Curr Opin Neurol 33(5):545–552

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This research was supported by the National Natural Science Foundation of China (grant number: 82171399).

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Authors and Affiliations

Authors

Contributions

Huan Yang: conception, study design, revision of the manuscript; Yi Li: manuscript writing, interpretation of the results and collection of data; Shumei Yang: data collection and manuscript revision; **aohua Dong, Fei Jiang, Kangzhi Chen, Qian Zhou, Haobin Cai participated in the collection of data.

Corresponding author

Correspondence to Huan Yang.

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None of the authors has any conflict of interest to disclose.

Ethics approval

The study complied with the Declaration of Helsinki. All participants were informed and signed the consent form for the study and was approved by the Medical Ethics Committee of the Hunan Medical Science Research Institute of **angya Hospital (202103207).

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All participants were informed and signed the consent form for the study.

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Li, Y., Yang, S., Dong, X. et al. Diagnostic value of antibody concentration ratio for treatment-refractory myasthenia gravis. Neurol Sci (2024). https://doi.org/10.1007/s10072-024-07601-w

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