Accessibility

LabCorp and its Specialty Testing Group, a fully integrated portfolio of specialty and esoteric testing laboratories.

Myasthenia Gravis Profile

CPT: 83519(x2); 86255

Test Includes

Acetylcholine Receptor (AChR)-binding Antibodies; Acetylcholine Receptor (AChR)-blocking Antibodies; Acetylcholine Receptor (AChR)-modulating Antibodies; Striational Antibodies.

Reflex Criteria: If Acetylcholine Receptor (AChR)-binding, blocking and modulating antibodies are normal will reflex to Muscle Specific Kinase (MuSK) Antibodies.


Specimen Requirements


Specimen

Serum


Volume

4 mL divided into two tubes


Minimum Volume

2 mL (Note: This volume does not allow for repeat testing.)


Container

Red-top tube or gel-barrier tube


Collection

Allow a minimum clotting time of 30 to 60 minutes with serum separation within 2 hours of collection. Send serum samples in plastic transport tubes.


Storage Instructions

Refrigerate.


Stability Requirements

Temperature

Period

Room temperature

7 days (stability provided by manufacturer or literature reference)

Refrigerated

14 days (stability provided by manufacturer or literature reference)

Frozen

14 days (stability provided by manufacturer or literature reference)

Freeze/thaw cycles

Stable x3 (stability provided by manufacturer or literature reference)


Patient Preparation

No isotopes administered 24 hours prior to venipuncture.


Causes for Rejection

Excessive hemolysis; chylous serum; recently administered radioisotopes; plasma specimen


Test Details


Use

Tests for the laboratory diagnosis of myasthenia gravis (MG).


Limitations

In rare cases AChR antibodies can be found in patients with other autoimmune disorders or with thymoma without MG.1

The causative autoantibody cannot be identified in up to ten percent of patients with MG.

This panel is RUO/IUO Yes due to the following test: Acetylcholine Receptor (AChR)-blocking Antibodies [085926].

Results for this test are for research purposes only by the assay's manufacturer. The performance characteristics of this product have not been established. Results should not be used as a diagnostic procedure without confirmation of the diagnosis by another medically established diagnostic product or procedure.


Methodology

See individual tests.


Additional Information

Myasthenia gravis (MG) is an acquired disorder of neuromuscular transmission that is characterized by skeletal muscle weakness and fatigability on exertion that is exacerbated by repeated muscle activity.2-7 This autoimmune disease is caused by antibodies directed toward receptors embedded in the motor endplate of the neuromuscular junction. Progressive weakness of the ocular muscles manifesting as asymmetric ptosis and variable diplopia are the presenting symptoms in 60% of patients.5,7 Many patients progress to more generalized weakness of peripheral limb muscles and muscles required for body posture, including facial and neck muscles. Bulbar muscle weakness compromises speaking (dysarthria), chewing and swallowing (dysphagia) and respiratory muscle weakness can lead to a myasthenic crisis where patients need to be ventilated artificially.8 Clinical symptoms may be restricted to one muscle group, in particular the eye muscles (ocular MG), or may become generalized (generalized MG).5-8

Patients with MG frequently have thymic abnormalities (thymic hyperplasia or thymoma).9 Ten to 15 percent of patients with MG patients have thymoma, and up to 50% of thymoma patients develop MG.9 It is thought that the thymus plays a role in MG pathogenesis and these patients respond well to the surgical removal of the thymus gland.10

Neonatal MG can occur as a result of trans-placental transit of antibodies from an affected mother to the fetus, or in some cases, due to antibody to the fetal form of AChR.11-13 In the latter case, the mother may be unaffected. It should be noted that the AChR antibody assays employed by LabCorp contain a mixture of adult and embryonic AChRs allowing for the detection of autoantibodies to both proteins. In most cases affected babies are born with a diminished ability to suck and generalized hypotonia. Decrease in utero feta movement caused by MG can also result in arthrogryposis multiplex congenital, a condition where the neonate suffers from contractures in more than two joints and in multiple body areas.

The majority of patients with MG have antibodies to the acetylcholine receptor (AChR) and, less frequently, to the other proteins at postsynaptic membrane of the neuromuscular junction.14-16 AChR antibodies impede neuromuscular transmission by a range of pathogenic mechanisms including the alteration of tissue architecture and/or by causing a reduction the density of functionality of AChRs.1,17-21 Three functionally different types of antibodies against muscle AChR can be measured.1,21-24

• AChR binding antibodies attach to the AChR activate the complement system result in in destruction and focal lysis of the neuromuscular junction leading to the destruction of AChR and AChR-related protein at the end-plate.1,20

• AChR blocking antibodies functionally block the binding of the neurotransmitter acetylcholine to the receptor.20 These antibodies usually occur in association with AChR-binding antibodies and have a higher prevalence in generalized MG compared with ocular MG.20

• AChR modulation antibodies crosslink receptor subunits in such as way as to cause the receptors to be internalized and degraded in a process known as antigenic modulation.20,22,25-27 Modulating antibodies are implicated with an increased risk of thymoma and the majority of patients with thymoma have modulating antibodies.28

Test for serum autoantibodies are highly sensitive and specific for generalized MG but lack sensitivity when there is pure ocular involvement.1,14,29-30 Approximately 85% of patients with generalized MG have detectable muscle AChR antibodies (of one or more types), while fewer patients with ocular MH have the antibodies (50-60%).4,30 In general, an elevated level of any one of the AChR-binding antibodies in a patient with compatible clinical features confirms the diagnosis of MG. Approximately 15 percent of individuals with confirmed myasthenia gravis have no measurable AChR binding, blocking, or modulating antibodies. Thirty-five percent of these patients (six percent of all MG patients) will have antibodies directed against a muscle-specific tyrosine kinase (MuSK).10,31 Autoantibodies levels do not generally correlate with disease severity. However, in individual patients, serial antibody titers tend to correlate with disease status.18,19,32-34

Autoantibodies directed against the contractile elements of striated muscle are found in 30% of adult patients with myasthenia gravis and in 80% of those with thymoma.35-37 Striational antibodies are associated with the late-onset MG subgroup and are rarely found in AChR antibody-negative MG.


Footnotes

1. Meriggioli MN, Sanders DB. Muscle autoantibodies in myasthenia gravis: beyond diagnosis? Expert Rev Clin Immunol. 2012 Jul;8(5):427-438.22882218
2. Berrih-Aknin S, Le Panse R. Myasthenia gravis: a comprehensive review of immune dysregulation and etiological mechanisms. J Autoimmun. 2014 Aug;52:90-100.24389034
3. Verschuuren JJ, Huijbers MG, Plomp JJ, et al. Pathophysiology of myasthenia gravis with antibodies to the acetylcholine receptor, muscle-specific kinase and low-density lipoprotein receptor-related protein 4. Autoimmun Rev. 2013 Jul;12(9):918-923.23535160
4. Phillips WD, Vincent A. Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms. F1000Res. 2016 Jun 27;5:F1000 Faculty Rev-1513.27408701
5. Gilhus NE, Skeie GO, Romi F, Lazaridis K, Zisimopoulou P, Tzartos S. Myasthenia gravis - autoantibody characteristics and their implications for therapy. Nat Rev Neurol. 2016 May;12(5):259-268.27103470
6. Hehir MK, Silvestri NJ. Generalized Myasthenia Gravis: Classification, Clinical Presentation, Natural History, and Epidemiology. Neurol Clin. 2018 May;36(2):253-260.29655448
7. Juel VC, Massey JM. Myasthenia gravis. Orphanet J Rare Dis. 2007 Nov 6;2:44.17986328
8. Skeie GO, Apostolski S, Evoli A, et al. Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol. 2010 Jul;17(7):893-902.20402760
9. Bernard C, Frih H, Pasquet F, et al. Thymoma associated with autoimmune diseases: 85 cases and literature review. Autoimmun Rev. 2016 Jan;15(1):82-92.26408958
10. Randomized Trial of Thymectomy in Myasthenia Gravis. Published Erratum. N Engl J Med. 2017 May 25;376(21):2097.28471717
11. Gilhus NE. Myasthenia Gravis Can Have Consequences for Pregnancy and the Developing Child. Front Neurol. 2020 Jun 12;11:554.32595594
12. Midelfart Hoff J, Midelfart A. Maternal myasthenia gravis: a cause for arthrogryposis multiplex congenita. J Child Orthop. 2015 Dec;9(6):433-435.26482518
13. Riemersma S, Vincent A, Beeson D, et al. Association of arthrogryposis multiplex congenita with maternal antibodies inhibiting fetal acetylcholine receptor function. J Clin Invest. 1996 Nov 15;98(10):2358-2363.8941654
14. Vincent A. Unravelling the pathogenesis of myasthenia gravis. Nat Rev Immunol. 2002 Oct;2(10):797-804.12360217
15. 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 Dec;48(12):1246-1252.4087000
16. Zisimopoulou P, Evangelakou P, Tzartos J, et al. A comprehensive analysis of the epidemiology and clinical characteristics of anti-LRP4 in myasthenia gravis. J Autoimmun. 2014 Aug;52:139-14524373505
17. Conti-Fine BM, Diethelm-Okita B, Ostlie N, et al. Immunopathogenesis of myasthenia gravis. In: Kaminski HJ, ed. Myasthenia Gravis and Related Disorders. 2nd ed. New York, NY: Humana; 2009:43-70.
18. Andreetta F, Rinaldi E, Bartoccioni E, et al. Diagnostics of myasthenic syndromes: detection of anti-AChR and anti-MuSK antibodies. Neurol Sci. 2017 Oct;38(Suppl 2):253-257.29030770
19. Paz ML, Barrantes FJ. Autoimmune Attack of the Neuromuscular Junction in Myasthenia Gravis: Nicotinic Acetylcholine Receptors and Other Targets. ACS Chem Neurosci. 2019 May 15;10(5):2186-2194.30916550
20. Conti-Fine BM, Milani M, Kaminski HJ. Myasthenia gravis: past, present, and future. J Clin Invest. 2006 Nov;116(11):2843-2854.17080188
21. Koneczny I, Herbst R. Myasthenia Gravis: Pathogenic Effects of Autoantibodies on Neuromuscular Architecture. Cells. 2019 Jul 2;8(7):671.31269763
22. Howard FM Jr, Lennon VA, Finley J, Matsumoto J, Elveback LR. Clinical correlations of antibodies that bind, block, or modulate human acetylcholine receptors in myasthenia gravis. Ann N Y Acad Sci. 1987;505:526-538.3479935
23. Kang SY, Oh JH, Song SK, Lee JS, Choi JC, Kang JH. Both binding and blocking antibodies correlate with disease severity in myasthenia gravis. Neurol Sci. 2015 Jul;36(7):1167-1171.25964166
24. Keefe D, Hess D, Bosco J, et al. A rapid, fluorescence-based assay for detecting antigenic modulation of the acetylcholine receptor on human cell lines. Cytometry B Clin Cytom. 2009 May;76(3):206-212.18825779
25. Beeson D, Jacobson L, Newsom-Davis J, Vincent A. A transfected human muscle cell line expressing the adult subtype of the human muscle acetylcholine receptor for diagnostic assays in myasthenia gravis. Neurology. 1996 Dec;47(6):1552-1555.8960744
26. Lyons BW, Wu LL, Astill ME, Wu JT. Development of an assay for modulating anti-acetylcholine receptor autoantibodies using human rhabdomyosarcoma cell line. J Clin Lab Anal. 1998;12(5):315-319.9773965
27. Lozier BK, Haven TR, Astill ME, Hill HR. Detection of acetylcholine receptor modulating antibodies by flow cytometry. Am J Clin Pathol. 2015 Feb;143(2):186-912.25596244
28. Pascuzzi RM. Pearls and pitfalls in the diagnosis and management of neuromuscular junction disorders. Semin Neurol. 2001 Dec;21(4):425-440.11774058
29. Benatar M. A systematic review of diagnostic studies in myasthenia gravis. Neuromuscul Disord. 2006 Jul;16(7):459-467.16793269
30. Leite MI, Waters P, Vincent A. Diagnostic use of autoantibodies in myasthenia gravis. Autoimmunity. 2010 Aug;43(5-6):371-379.20380582
31. Guptill JT, Sanders DB, Evoli A. Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts. Muscle Nerve. 2011 Jul;44(1):36-40.21674519
32. Peeler CE, De Lott LB, Nagia L, Lemos J, Eggenberger ER, Cornblath WT. Clinical Utility of Acetylcholine Receptor Antibody Testing in Ocular Myasthenia Gravis. JAMA Neurol. 2015 Oct;72(10):1170-1174.26258604
33. Strijbos E, Verschuuren JJGM, Kuks JBM. Serum Acetylcholine Receptor Antibodies Before the Clinical Onset of Myasthenia Gravis. J Neuromuscul Dis. 2018;5(2):261-264.29865092
34. Sanders DB, Burns TM, Cutter GR, et al. Does change in acetylcholine receptor antibody level correlate with clinical change in myasthenia gravis? Muscle Nerve. 2014 Apr;49(4):483-486.23835683
35. Cikes N, Momoi MY, Williams CL, et al. Striational autoantibodies: quantitative detection by enzyme immunoassay in myasthenia gravis, thymoma, and recipients of D-penicillamine or allogeneic bone marrow. Mayo Clin Proc. 1988 May;63(5):474-481.3283472
36. Romi F, Skeie GO, Gilhus NE, Aarli JA. Striational antibodies in myasthenia gravis: reactivity and possible clinical significance. Arch Neurol. 2005 Mar;62(3):442-446.15767509
37. Vernino S, Lennon VA. Autoantibody profiles and neurological correlations of thymoma. Clin Cancer Res. 2004 Nov 1;10(21):7270-727515534101

For Providers

Please login to order a test

Order a Test

© 2020 Laboratory Corporation of America® Holdings and Lexi-Comp Inc. All Rights Reserved.

CPT Statement/Profile Statement

The LOINC® codes are copyright © 1994-2020, Regenstrief Institute, Inc. and the Logical Observation Identifiers Names and Codes (LOINC) Committee. Permission is granted in perpetuity, without payment of license fees or royalties, to use, copy, or distribute the LOINC® codes for any commercial or non-commercial purpose, subject to the terms under the license agreement found at https://loinc.org/license/. Additional information regarding LOINC® codes can be found at LOINC.org, including the LOINC Manual, which can be downloaded at LOINC.org/downloads/files/LOINCManual.pdf