Passive transfer of experimental autoimmune myasthenia gravis by monoclonal antibodies to the main immunogenic region of the acetylcholine receptor

Tzartos, Socrates J.; Hochschwender, Susan M.; Vasquez, Peter; Lindstrom, Jon

doi:10.1016/0165-5728(87)90092-0

Cited by 169 publications

(87 citation statements)

References 38 publications

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“…injection of 0.75-1 mg/kg resulted in high clinical scores (score 3 of a possible 4) without significant lethality (data not shown). Disease progression was similar to that described previously, with symptoms typically starting at 12 h, peaking at 48 h and gradually disappearing by 72 h post-mAb35 injection (39). EAMG symptoms were almost completely prevented when 30 mg/kg 1G3 was administered twice at 24 and 2 h before mAb35 injection (Fig.…”

Section: Blockade Of Fcrn Inhibits Disease Symptoms In Passive Eamgsupporting

confidence: 60%

Amelioration of Experimental Autoimmune Myasthenia Gravis in Rats by Neonatal FcR Blockade

García

Santoro

et al. 2007

The Journal of Immunology

106

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The neonatal FcR (FcRn) plays a critical role in IgG homeostasis by protecting it from a lysosomal degradation pathway. It has been shown that IgG has an abnormally short half-life in FcRn-deficient mice and that FcRn blockade significantly increases the catabolism of serum IgG in mice. Therefore, reduction of serum IgG half-life may have therapeutic benefits in Ab-mediated autoimmune diseases. We have studied the therapeutic effects of an anti-rat FcRn mAb, 1G3, in two rat models of myasthenia gravis, a prototypical Ab-mediated autoimmune disease. Passive experimental autoimmune myasthenia gravis was induced by administration of an anti-acetylcholine receptor (AChR) mAb, and it was shown that treatment with 1G3 resulted in dose-dependent amelioration of the disease symptoms. In addition, the concentration of pathogenic Ab in the serum was reduced significantly. The effect of 1G3 was also studied in an active model of experimental autoimmune myasthenia gravis in which rats were immunized with AChR. Treatment with 1G3 significantly reduced the severity of the disease symptoms as well as the levels of total IgG and anti-AChR IgG relative to untreated animals. These data suggest that FcRn blockade may be an effective way to treat Ab-mediated autoimmune diseases.

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Section: Blockade Of Fcrn Inhibits Disease Symptoms In Passive Eamgsupporting

confidence: 60%

Amelioration of Experimental Autoimmune Myasthenia Gravis in Rats by Neonatal FcR Blockade

García

Santoro

et al. 2007

The Journal of Immunology

106

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“…The anti-AChR antibody response in MG is also polyclonal (1-4), and even antibodies directed to the same AChR epitope have different idiotypes (68,69). However, it is likely that only antibodies against particular AChR epitopes, which should include the MIR (70,71 ), cause AChR destruction and myasthenic symptoms, as suggested by the lack of correlation between the antibody titer and the severity of MG ( 1-4, 72, 73) and by experiments that tested the ability -f different antiAChR (74). It is possible that among the many anti-AChR Th clones present in MG patients, only those directed against particular epitopes are involved in the development of MG symptoms, due to the preferential pairing with B cells secreting antibodies ofhigh pathogenetic potential.…”

Section: A293-308--------v I N T H H R S P S T H V Ss Ss Hh Rs Ps P Rmentioning

confidence: 99%

T helper cell recognition of muscle acetylcholine receptor in myasthenia gravis. Epitopes on the gamma and delta subunits.

et al. 1993

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We tested the response of CD4' cells and/or total lymphocytes from the blood of 22 myasthenic patients and 10 healthy controls to overlapping synthetic peptides, 20 residues long, to screen the sequence of the y and 5 subunits of human muscle acetylcholine receptor (AChR). The oy subunit is part of the AChR expressed in embryonic muscle and is substituted in the AChRs of most adult muscles by an e subunit. The 5 subunit is present in both embryonic and adult AChRs. Adult extrinsic ocular muscles, which are preferentially and sometimes uniquely affected by myasthenic symptoms, and thymus, which has a still obscure but important role in the pathogenesis of myasthenia gravis, express the embryonic 'y subunit. AntiAChR CD4+ responses were more easily detected after CD8+ depletion. All responders recognized epitopes on both the y and a subunits and had severe symptoms. In four patients the CD4 + cell response was tested twice, when the symptoms were severe and during a period of remission. Consistently, the response was only detectable, or larger, when the patients were severely affected. (J. Clin. Invest. 1993. 92:1055-1067

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“…mAb 210 Tzartos et al, 1987;Wang et al, 1996) was used to test for the presence of α3/α5-nAChRs; mAb 313 (Whiting et al, 1991) was used to test for α3-A. L. Obaid and others Nicotinic receptors in guinea-pig gut nAChRs; mAb 299 (Whiting and Lindstrom, 1988) was used to test for α4-nAChRs; mAb 295 (Whiting and Lindstrom, 1988) was used to test for β2-nAChRs; and mAb 337 (Nelson et al, 2001) was used to test for β4-nAChRs.…”

Section: Liquid-phase Riasmentioning

confidence: 99%

Optical studies of nicotinic acetylcholine receptor subtypes in the guinea-pig enteric nervous system

Obaid

Nelson

Lindstrom

et al. 2005

Journal of Experimental Biology

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ErratumObaid, A. L., Nelson, M. E., Lindstrom, J. and Salzberg, B. M. (2005). Optical studies of nicotinic acetylcholine receptor subtypes in the guinea-pig enteric nervous system. J. Exp. Biol. 208, 2981-3001. In the original published on-line version of this paper, the acceptance date was incorrect. It should have read 2 June 2005. The error has been rectified and the current on-line version and print versions are correct.We apologise to authors and readers for any inconvenience this may have caused. 2981Decoding the structure and function of native nicotinic acetylcholine receptors (nAChRs) is complex. Although the expression of defined combinations of nAChR-subunits in Xenopus oocytes permits the comparison of pharmacological properties of individual nAChR-subtypes, single neurones often express more than one subtype, making the physiological roles of nAChRs in intact neuronal networks difficult to assess (Colquhoun and Patrick, 1997). The function of a given nAChR depends upon its pre-, post-or peri-synaptic location as well as the activity of neighbouring non-nicotinic receptors. In addition, the properties of any neuronal ensemble depend not only on the intrinsic conductances of its neurones and the specific attributes of its many synapses but also on the complex and nonlinear dynamic interactions that result from the multiple parallel connectivity of its component cells (Parsons et al., 1991). Therefore, to understand nicotinic responses at the network level, it is necessary to record at high spatial and temporal resolution to characterize the behaviour of individual neurones and at lower spatial resolution to capture a panoramic view of network activity and to assess the directionality of the nicotinic pathways along the circumferential as well as the longitudinal axes.The enteric nervous system (ENS) regulates most gastrointestinal functions. Its neurones are clustered in ganglia that interconnect to form distinct plexuses in the gut wall: the myenteric plexus lies between the longitudinal and circular muscle layers, and the submucous plexus between the circular muscle layer and the mucosa. The behaviour of the effector Nicotinic transmission in the enteric nervous system (ENS) is extensive, but the role of individual nicotinic acetylcholine receptor (nAChR) subtypes in the functional connectivity of its plexuses has been elusive. Using monoclonal antibodies (mAbs) against neuronal α3-, α4-, α3/α5-, β2-, β4-and α7-subunits, combined with radioimmunoassays and immunocytochemistry, we demonstrate that guinea-pig enteric ganglia contain all of these nAChR-subunits with the exception of α4, and so, differ from mammalian brain. This information alone, however, is insufficient to establish the functional role of the identified nAChR-subtypes within the enteric networks and, ultimately, their specific contributions to gastrointestinal physiology. We have used voltagesensitive dyes and a high-speed CCD camera, in conjunction with specific antagonists to various nAChRs, to elucidate some of the distinct cont...

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Passive transfer of experimental autoimmune myasthenia gravis by monoclonal antibodies to the main immunogenic region of the acetylcholine receptor

Cited by 169 publications

References 38 publications

Amelioration of Experimental Autoimmune Myasthenia Gravis in Rats by Neonatal FcR Blockade

Amelioration of Experimental Autoimmune Myasthenia Gravis in Rats by Neonatal FcR Blockade

T helper cell recognition of muscle acetylcholine receptor in myasthenia gravis. Epitopes on the gamma and delta subunits.

Optical studies of nicotinic acetylcholine receptor subtypes in the guinea-pig enteric nervous system

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