Repeated Acetylcholine Receptor Antibody-concentrations and Association to Clinical Myasthenia Gravis Development

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Dec 3

PMID 25464006

Citations 21

Authors

Anne Taraldsen Heldal

Geir Egil Eide

Fredrik Romi

Jone Furlund Owe

Nils Erik Gilhus

Affiliations

Soon will be listed here.

Abstract

Introduction: We aimed to examine the longitudinal association between Myasthenia Gravis (MG) clinical severity and concentration of acetylcholine receptor (AChR)-antibodies to evaluate if AChR-antibody variations correlate to disease severity. A positive AChR-antibody test is specific for MG.

Material And Methods: All patients from western Norway who had two or more AChR- antibody tests in the period 1983-2013 were identified. The Myasthenia Gravis Foundation of America (MGFA) Clinical Classification was used to grade disease development. Multiple ordinal logistic regression analysis was used to estimate a possible predictive effect for AChR-antibody concentration on MGFA classification result.

Results: In 67 patients two or more AChR-antibody tests with a corresponding MGFA-score were performed, with a total of 309 tests. 56 patients were treated with immunosuppressive drugs and 11 by pyridostigmine only. There was a positive association between concentration of AChR-antibodies and longitudinal MGFA-score for the subgroup with immunosuppressive treatment, but not for those treated with pyridostigmine only. This association between AChR-antibody concentration and MGFA score declined with increasing time since onset (p = 0.005 for the interaction of group×time×concentration).

Conclusions: For MG patients with immunosuppressive treatment, repeated AChR-antibody measurements give information about clinical development, and can therefore be of support in therapeutic decisions.

Citing Articles

Exploring the clinical significance of anti-acetylcholine receptor antibody titers, changes, and change rates in Myasthenia Gravis.

Luo L, Zhu X, Wen C, Guo Y, Yang J, Wei D Front Neurol. 2025; 15:1506845.

PMID: 39882373 PMC: 11774727. DOI: 10.3389/fneur.2024.1506845.

Autoantibodies in neuromuscular disorders: a review of their utility in clinical practice.

Loser V, Vicino A, Theaudin M Front Neurol. 2024; 15:1495205.

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

Li Y, Yang S, Dong X, Duan W, Jiang F, Chen K Neurol Sci. 2024; 45(10):5033-5041.

PMID: 38780854 DOI: 10.1007/s10072-024-07601-w.

Editorial: Phenotypes of myasthenia gravis, volume II.

Li H, Gilhus N, Xue Q, Gao F Front Neurol. 2023; 14:1335308.

PMID: 38073651 PMC: 10704596. DOI: 10.3389/fneur.2023.1335308.

Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis.

Hussain F, Piragasam R, Sarker H, Blackmore D, Yacyshyn E, Fernandez-Patron C Sci Rep. 2023; 13(1):21229.

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References

Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A . Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med. 2001; 7(3):365-8. DOI: 10.1038/85520. View

Meriggioli M, Sanders D . Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol. 2009; 8(5):475-90. PMC: 2730933. DOI: 10.1016/S1474-4422(09)70063-8. View

Leite M, Waters P, Vincent A . Diagnostic use of autoantibodies in myasthenia gravis. Autoimmunity. 2010; 43(5-6):371-9. DOI: 10.3109/08916930903541208. View

Vincent A, Clover L, Buckley C, Evans J, Rothwell P . Evidence of underdiagnosis of myasthenia gravis in older people. J Neurol Neurosurg Psychiatry. 2003; 74(8):1105-8. PMC: 1738592. DOI: 10.1136/jnnp.74.8.1105. View

Vincent A, Wood H . Antibody specificity in myasthenia gravis. Monogr Allergy. 1988; 25:33-40. View

Heinemann S, Bevan S, Kullberg R, Lindstrom J, Rice J . Modulation of acetylcholine receptor by antibody against the receptor. Proc Natl Acad Sci U S A. 1977; 74(7):3090-4. PMC: 431419. DOI: 10.1073/pnas.74.7.3090. View

Andersen J, Pehrson R, Tolmachev V, Daba M, Abrahmsen L, Ekblad C . Extending half-life by indirect targeting of the neonatal Fc receptor (FcRn) using a minimal albumin binding domain. J Biol Chem. 2010; 286(7):5234-41. PMC: 3037636. DOI: 10.1074/jbc.M110.164848. View

Ferrero B, Aimo G, Pagni R, Bergamasco B, Bongioanni M, BERGAMINI L . Modified and improved anti-acetylcholine receptor (AchR) antibody assay: comparison of analytical and clinical performance with conventional anti-AChR antibody assay. Clin Chem. 1997; 43(5):824-31. View

Cavalcante P, Bernasconi P, Mantegazza R . Autoimmune mechanisms in myasthenia gravis. Curr Opin Neurol. 2012; 25(5):621-9. DOI: 10.1097/WCO.0b013e328357a829. View

10.

Jaretzki 3rd A, Barohn R, Ernstoff R, Kaminski H, KEESEY J, Penn A . Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Ann Thorac Surg. 2000; 70(1):327-34. DOI: 10.1016/s0003-4975(00)01595-2. View

11.

Tuzun E, Christadoss P . Complement associated pathogenic mechanisms in myasthenia gravis. Autoimmun Rev. 2013; 12(9):904-11. DOI: 10.1016/j.autrev.2013.03.003. View

12.

Higuchi O, Hamuro J, Motomura M, Yamanashi Y . Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis. Ann Neurol. 2011; 69(2):418-22. DOI: 10.1002/ana.22312. View

13.

Skeie G, Apostolski S, Evoli A, Gilhus N, Illa I, Harms L . Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol. 2010; 17(7):893-902. DOI: 10.1111/j.1468-1331.2010.03019.x. View

14.

Vincent A, Newsom-Davis J . Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J Neurol Neurosurg Psychiatry. 1985; 48(12):1246-52. PMC: 1028609. DOI: 10.1136/jnnp.48.12.1246. View

15.

Heldal A, Owe J, Gilhus N, Romi F . Seropositive myasthenia gravis: a nationwide epidemiologic study. Neurology. 2009; 73(2):150-1. DOI: 10.1212/WNL.0b013e3181ad53c2. View

16.

Zhang B, Tzartos J, Belimezi M, Ragheb S, Bealmear B, Lewis R . Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch Neurol. 2011; 69(4):445-51. DOI: 10.1001/archneurol.2011.2393. View

17.

Andersen J, Engeland A, Owe J, Gilhus N . Myasthenia gravis requiring pyridostigmine treatment in a national population cohort. Eur J Neurol. 2010; 17(12):1445-50. DOI: 10.1111/j.1468-1331.2010.03089.x. View

18.

Pevzner A, Schoser B, Peters K, Cosma N, Karakatsani A, Schalke B . Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis. J Neurol. 2011; 259(3):427-35. DOI: 10.1007/s00415-011-6194-7. View

19.

Mori S, Shigemoto K . Mechanisms associated with the pathogenicity of antibodies against muscle-specific kinase in myasthenia gravis. Autoimmun Rev. 2013; 12(9):912-7. DOI: 10.1016/j.autrev.2013.03.005. View

20.

Walter S, Eliasziw M, Donner A . Sample size and optimal designs for reliability studies. Stat Med. 1998; 17(1):101-10. DOI: 10.1002/(sici)1097-0258(19980115)17:1<101::aid-sim727>3.0.co;2-e. View