MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4

Proceedings of the National Academy of Sciences of the United States of America

Volumn 110, Issue 51, 2013, Pages 20783-20788

  Huijbers, Maartje G ^a   Zhang, Wei ^a   Klooster, Rinse ^a   Niks, Erik H ^a   Friese, Matthew B ^a   Straasheijm, Kirsten R ^a   Thijssen, Peter E ^a   Vrolijk, Hans ^b   Plomp, Jaap J ^a,b   Vogels, Pauline ^a   Losen, Mario ^c   Van Der Maarel, Silvère M ^a   Burden, Steven J ^a   Verschuuren, Jan J ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^b NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c MAASTRICHT UNIVERSITY   (Netherlands)

Author keywords

Activation loop; Dok7; Insulin receptor; Neuromuscular junction; Rapsyn

Indexed keywords

AGRIN; AUTOANTIBODY; IMMUNOGLOBULIN G4; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 4; MUSCLE SPECIFIC KINASE; UNCLASSIFIED DRUG;

ADOLESCENT; ADULT; AGED; AMINO ACID SEQUENCE; ANTIBODY TITER; ANTIGEN BINDING; ARTICLE; CELL SURFACE; CHILD; CLINICAL ARTICLE; CONTROLLED STUDY; DIMERIZATION; FEMALE; HUMAN; IMMUNOREACTIVITY; INTERNALIZATION; MALE; MYASTHENIA GRAVIS; PRESCHOOL CHILD; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN PHOSPHORYLATION; SCHOOL CHILD;

EID: 84890823064     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1313944110     Document Type: Article

References (54)

1. Lennon VA, Lindstrom JM, Seybold ME (1975) Experimental autoimmune myasthenia: A model of myasthenia gravis in rats and guinea pigs. J Exp Med 141(6):1365-1375.
2. Lindstrom JM, Engel AG, Seybold ME, Lennon VA, Lambert EH (1976) Pathological mechanisms in experimental autoimmune myasthenia gravis. II. Passive transfer of experimental autoimmune myasthenia gravis in rats with anti-Acetylcholine receptor antibodies. J Exp Med 144(3):739-753.
3. Rødgaard A, Nielsen FC, Djurup R, Somnier F, Gammeltoft S (1987) Acetylcholine receptor antibody in myasthenia gravis: Predominance of IgG subclasses 1 andd Clin Exp Immunol 67(1):82-88.
4. Engel AG, Arahata K (1987) The membrane attack complex of complement at the endplate in myasthenia gravis. Ann N Y Acad Sci 505:326-332.
5. Drachman DB, Angus CW, Adams RN, Michelson JD, Hoffman GJ (1978) Myasthenic antibodies cross-Link acetylcholine receptors to accelerate degradation. N Engl J Med 298(20):1116-1122.
6. Drachman DB, Adams RN, Josifek LF, Self SG (1982) Functional activities of autoantibodies to acetylcholine receptors and the clinical severity of myasthenia gravis. N Engl J Med 307(13):769-775.
7. Christadoss P (1988) C5 gene influences the development of murine myasthenia gravis. J Immunol 140(8):2589-2592.
8. Papanastasiou D, Poulas K, Kokla A, Tzartos SJ (2000) Prevention of passively transferred experimental autoimmune myasthenia gravis by Fab fragments of monoclonal antibodies directed against the main immunogenic region of the acetylcholine receptor. J Neuroimmunol 104(2):124-132.
9. Burden SJ, Yumoto N, Zhang W (2013) The role of MuSK in synapse formation and neuromuscular disease. Cold Spring Harb Perspect Biol 5(5):a009167.
10. DeChiara TM, et al. (1996) The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo. Cell 85(4):501-512.
11. Hoch W, et al. (2001) Auto-Antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 7(3):365-368.
12. Klooster R, et al. (2012) Muscle-Specific kinase myasthenia gravis IgG4 autoantibodies cause severe neuromuscular junction dysfunction in mice. Brain 135(Pt 4):1081-1101.
13. McConville J, et al. (2004) Detection and characterization of MuSK antibodies in seronegative myasthenia gravis. Ann Neurol 55(4):580-584.
14. Niks EH, et al. (2008) Clinical fluctuations in MuSK myasthenia gravis are related to antigen-Specific IgG4 instead of IgG1. J Neuroimmunol 195(1-2):151-156.
15. van der Neut Kolfschoten M, et al. (2007) Anti-Inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science 317(5844):1554-1557.
16. Mori S, et al. (2012) Antibodies against muscle-Specific kinase impair both presynaptic and postsynaptic functions in a murine model of myasthenia gravis. Am J Pathol 180(2):798-810.
17. Sanes JR, Lichtman JW (2001) Induction, assembly, maturation and maintenance of a postsynaptic apparatus. Nat Rev Neurosci 2(11):791-805.
18. Kim N, et al. (2008) Lrp4 is a receptor for Agrin and forms a complex with MuSK. Cell 135(2):334-342.
19. Zhang B, et al. (2008) LRP4 serves as a coreceptor of agrin. Neuron 60(2):285-297.
20. ZhangW, Coldefy AS, Hubbard SR, Burden SJ (2011) Agrin binds to the N-Terminal region of Lrp4 protein and stimulates association between Lrp4 and the first immunoglobulinlike domain in muscle-Specific kinase (MuSK). J Biol Chem 286(47):40624-40630.
21. Hallock PT, et al. (2010) Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L. Genes Dev 24(21):2451-2461.
22. Hamuro J, et al. (2008) Mutations causing DOK7 congenital myasthenia ablate functional motifs in Dok-7. J Biol Chem 283(9):5518-5524.
23. Okada K, et al. (2006) The muscle protein Dok-7 is essential for neuromuscular synaptogenesis. Science 312(5781):1802-1805.
24. Stiegler AL, Burden SJ, Hubbard SR (2006) Crystal structure of the agrin-Responsive immunoglobulin-Like domains 1 and 2 of the receptor tyrosine kinase MuSK. J Mol Biol 364(3):424-433.
25. Yumoto N, Kim N, Burden SJ (2012) Lrp4 is a retrograde signal for presynaptic differentiation at neuromuscular synapses. Nature 489(7416):438-442.
26. Hesser BA, Henschel O, Witzemann V (2006) Synapse disassembly and formation of new synapses in postnatal muscle upon conditional inactivation of MuSK. Mol Cell Neurosci 31(3):470-480.
27. Kong XC, Barzaghi P, Ruegg MA (2004) Inhibition of synapse assembly in mammalian muscle in vivo by RNA interference. EMBO Rep 5(2):183-188.
28. Im SH, Barchan D, Fuchs S, Souroujon MC (2000) Mechanism of nasal tolerance induced by a recombinant fragment of acetylcholine receptor for treatment of experimental myasthenia gravis. J Neuroimmunol 111(1-2):161-168.
29. Lennon VA, Lambert EH, Leiby KR, Okarma TB, Talib S (1991) Recombinant human acetylcholine receptor alpha-Subunit induces chronic experimental autoimmune myasthenia gravis. J Immunol 146(7):2245-2248.
30. Lindstrom J, Einarson B (1979) Antigenic modulation and receptor loss in experimental autoimmune myasthenia gravis. Muscle Nerve 2(3):173-179.
31. Luo J, et al. (2009) Main immunogenic region structure promotes binding of conformation-Dependent myasthenia gravis autoantibodies, nicotinic acetylcholine receptor conformation maturation, and agonist sensitivity. J Neurosci 29(44):13898-13908.
32. Mahler M, Fritzler MJ (2010) Epitope specificity and significance in systemic autoimmune diseases. Ann N Y Acad Sci 1183:267-287.
33. Till JH, et al. (2002) Crystal structure of the MuSK tyrosine kinase: Insights into receptor autoregulation. Structure 10(9):1187-1196.
34. Kawakami Y, et al. (2011) Anti-MuSK autoantibodies block binding of collagen Q to MuSK. Neurology 77(20):1819-1826.
35. Takamori M, Nakamura T, Motomura M (2013) Antibodies against Wnt receptor of muscle-Specific tyrosine kinase in myasthenia gravis. J Neuroimmunol 254(1-2): 183-186.
36. Shigemoto K, et al. (2006) Induction of myasthenia by immunization against musclespecific kinase. J Clin Invest 116(4):1016-1024.
37. Mori S, et al. (2012) Divalent and monovalent autoantibodies cause dysfunction of MuSK by distinct mechanisms in a rabbit model of myasthenia gravis. J Neuroimmunol 244(1-2):1-7.
38. Dangl JL, et al. (1988) Segmental flexibility and complement fixation of genetically engineered chimeric human, rabbit and mouse antibodies. EMBO J 7(7):1989-1994.
39. Oi VT, et al. (1984) Correlation between segmental flexibility and effector function of antibodies. Nature 307(5947):136-140.
40. Cole RN, et al. (2010) Patient autoantibodies deplete postsynaptic muscle-Specific kinase leading to disassembly of the ACh receptor scaffold and myasthenia gravis in mice. J Physiol 588(Pt 17):3217-3229.
41. Amenta AR, et al. (2012) Biglycan is an extracellular MuSK binding protein important for synapse stability. J Neurosci 32(7):2324-2334.
42. Cartaud A, et al. (2004) MuSK is required for anchoring acetylcholinesterase at the neuromuscular junction. J Cell Biol 165(4):505-515.
43. Luo ZG, et al. (2002) Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1. Neuron 35(3):489-505.
44. Ngo ST, Cole RN, Sunn N, Phillips WD, Noakes PG (2012) Neuregulin-1 potentiates agrin-Induced acetylcholine receptor clustering through muscle-Specific kinase phosphorylation. J Cell Sci 125(Pt 6):1531-1543.
45. Viegas S, et al. (2012) Passive and active immunization models of MuSK-Ab positive myasthenia: Electrophysiological evidence for pre and postsynaptic defects. Exp Neurol 234(2):506-512.
46. Valenzuela DM, et al. (1995) Receptor tyrosine kinase specific for the skeletal muscle lineage: Expression in embryonic muscle, at the neuromuscular junction, and after injury. Neuron 15(3):573-584.
47. Higuchi O, Hamuro J, Motomura M, Yamanashi Y (2011) Autoantibodies to lowdensity lipoprotein receptor-Related protein 4 in myasthenia gravis. Ann Neurol 69(2): 418-422.
48. Pevzner A, et al. (2012) Anti-LRP4 autoantibodies in AChR-And MuSK-Antibodynegative myasthenia gravis. J Neurol 259(3):427-435.
49. Zhang B, et al. (2012) Autoantibodies to lipoprotein-Related protein 4 in patients with double-Seronegative myasthenia gravis. Arch Neurol 69(4):445-451.
50. Di Zenzo G, et al. (2012) Pemphigus autoantibodies generated through somatic mutations target the desmoglein-3 cis-Interface. J Clin Invest 122(10):3781-3790.
51. Beck LH, Jr., et al. (2009) M-Type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 361(1):11-21.
52. Irani SR, et al. (2012) Morvan syndrome: Clinical and serological observations in 29 cases. Ann Neurol 72(2):241-255.
53. Khosroshahi A, Bloch DB, Deshpande V, Stone JH (2010) Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-Related systemic disease. Arthritis Rheum 62(6):1755-1762.
54. Herbst R, Burden SJ (2000) The juxtamembrane region of MuSK has a critical role in agrin-Mediated signaling. EMBO J 19(1):67-77.