title: Effect of sera from seronegative myasthenia gravis patients on neuromuscular junctions.
abstract: About 85 % of patients with generalized myasthenia gravis (MG) have anti-nicotinic acetylcholine receptor (nAChR) antibodies in their sera (seropositive MG; SPMG). The other 15 % (seronegative MG; SNMG) are also considered to have antibody-mediated disease, but the nature of the antibodies in SNMG is not fully understood. We investigated the effect of sera from patients with MG on spontaneous muscle action potentials and acetylcholine (ACh)-induced potentials, and we examined the localization of epitopes recognized by SPMG sera or SNMG sera. SPMG sera and SNMG sera inhibited spontaneous muscle action potentials and ACh-induced potentials in the spinal-muscle co-culture system. However, spontaneous muscle action potentials and ACh-induced potentials in the neuromuscular junctions were strongly blocked by SPMG serum, whereas they were weakly blocked by SNMG serum. Both types of sera reacted strongly with the neuromuscular junctions in normal rat muscles, as shown by double immunostaining with serum and α-bungarotoxin. The SPMG epitope remained in the neuromuscular junctions, whereas that of SNMG disappeared after denervation of the sciatic nerve. Therefore, we suggest that the skeletal muscle weakness in SNMG may be due to an interaction with presynaptic neuromuscular transmission and nAChR.
authors: Department of Pharmacotherapeutics, Showa Pharmaceutical University, Higashitamagawagakuen, Machida, Tokyo, 194-8543, Japan.
authors: Rumi
authors: R
authors: Sato
authors: Shiho
authors: S
authors: Imamoto
authors: Iku
authors: I
authors: Utsnomiya
authors: Terumasa
authors: T
authors: Chiba
authors: Kyoji
authors: K
authors: Taguchi
authors: Kenji
authors: K
authors: Abe
authors: Keiko
authors: K
authors: Tanaka
authors: Tadashi
authors: T
authors: Miyatake
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D000368:Aged; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002038:Bungarotoxins / Q000276:immunology; D018679:Cholinergic Agonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology; D009157:Myasthenia Gravis / Q000097:blood* / Q000276:immunology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology; D013116:Spinal Cord / Q000166:cytology; D055815:Young Adult
chemical_list: D000906:Antibodies; D002038:Bungarotoxins; D018679:Cholinergic Agonists; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D000109:Acetylcholine
references: J Neuroimmunol. 1993 Mar;43(1-2):145-9
references: 8384634
references: Postgrad Med J. 1985 Aug;61(718):725-7
references: 4034463
references: Physiol Rev. 1984 Oct;64(4):1162-239
references: 6208568
references: J Physiol. 1996 Apr 1;492 ( Pt 1):107-14
references: 8730587
references: Pflugers Arch. 1994 Oct;428(5-6):492-8
references: 7838671
references: Neurol Res. 2003 Jan;25(1):58-62
references: 12564127
references: Neurology. 2000 Jan 25;54(2):474-9
references: 10668717
references: Ann Neurol. 2000 Apr;47(4):504-10
references: 10762162
references: Nature. 1986 May 22-28;321(6068):406-11
references: 2423878
references: Biochim Biophys Acta. 1975 May 30;393(1):66-77
references: 1138925
references: Clin Neurophysiol. 2006 Jul;117(7):1434-43
references: 16737845
references: Proc Natl Acad Sci U S A. 1979 Jan;76(1):504-8
references: 85302
references: Nat Med. 2001 Mar;7(3):365-8
references: 11231638
references: Cell. 1996 May 17;85(4):501-12
references: 8653786
references: Cell. 1996 May 17;85(4):513-23
references: 8653787
references: Semin Neurol. 2004 Mar;24(1):125-33
references: 15229799
references: Ann Neurol. 1998 Apr;43(4):458-64
references: 9546326
references: N Engl J Med. 1994 Jun 23;330(25):1797-810
references: 8190158
references: Lancet. 2001 Jun 30;357(9274):2122-8
references: 11445126
references: Brain. 2008 Jul;131(Pt 7):1940-52
references: 18515870
references: J Membr Biol. 1983;76(2):123-8
references: 6315946
references: J Neuroimmunol. 1988 Aug;19(1-2):141-8
references: 2456301
references: J Neuroimmunol. 1996 Feb;64(2):179-83
references: 8632060
references: J Neurol. 2012 Mar;259(3):427-35
references: 21814823
references: J Physiol. 1989 Apr;411:271-83
references: 2614725
references: Neurology. 1988 Dec;38(12):1890-2
references: 2461538
references: Can J Physiol Pharmacol. 1980 May;58(5):445-58
references: 6998547
references: Arch Neurol. 1976 Nov;33(11):751-8
references: 185992
references: J Neurol Sci. 2004 Oct 15;225(1-2):91-8
references: 15465091
references: Ann N Y Acad Sci. 2008;1132:84-92
references: 18567857
references: Nature. 1978 Jun 8;273(5662):469-71
references: 661959
references: Brain Res. 2005 Feb 9;1034(1-2):62-70
references: 15713260
references: Scand J Immunol. 1996 Jan;43(1):81-7
references: 8560200
references: J Neuroimmunol. 2007 Apr;185(1-2):136-44
references: 17335909
references: J Neurol Sci. 1991 Mar;102(1):39-45
references: 1856731
references: Nature. 1977 Sep 15;269(5625):218-22
references: 201850
references: J Neurol Sci. 1995 Jun;130(2):165-70
references: 8586981