PMID- 15833370 OWN - NLM STAT- MEDLINE DCOM- 20050705 LR - 20220129 IS - 0165-5728 (Print) IS - 0165-5728 (Linking) VI - 162 IP - 1-2 DP - 2005 May TI - Inhibition of acetylcholine receptor function by seronegative myasthenia gravis non-IgG factor correlates with desensitisation. PG - 149-56 AB - 15% of myasthenia gravis (MG) patients do not have antibodies against the acetylcholine receptor (AChR). Some of these "seronegative" MG patients have antibodies against muscle specific kinase (MuSK), and many have a non-IgG factor that acutely inhibits AChR function in a muscle-like cell line, CN21. Here we show, using mainly one plasma negative for both AChR and MuSK antibodies, that the inhibitory effect of the non-IgG fraction correlates well with the desensitisation caused by 100 microM nicotine, and is found also when AChRs are expressed in a non-muscle cell line (HEK). Moreover, a similar effect was seen with M3C7-a monoclonal antibody against human AChR. The results suggest that, rather than acting indirectly as previously proposed, the SNMG factor may bind directly to an allosteric site that induces or enhances AChR desensitisation. FAU - Spreadbury, Ian AU - Spreadbury I AD - Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom. FAU - Kishore, Uday AU - Kishore U FAU - Beeson, David AU - Beeson D FAU - Vincent, Angela AU - Vincent A LA - eng GR - G117/490/MRC_/Medical Research Council/United Kingdom PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - J Neuroimmunol JT - Journal of neuroimmunology JID - 8109498 RN - 0 (Antibodies) RN - 0 (Autoantibodies) RN - 0 (Nicotinic Agonists) RN - 0 (Receptors, Cholinergic) RN - 6M3C89ZY6R (Nicotine) RN - EC 2.7.10.1 (MUSK protein, human) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Adult MH - Antibodies/pharmacology MH - Autoantibodies/blood/immunology/*pharmacology MH - Cell Line, Tumor MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Male MH - Membrane Potentials/drug effects/physiology MH - Myasthenia Gravis/*immunology MH - Nicotine/pharmacology MH - Nicotinic Agonists/pharmacology MH - Patch-Clamp Techniques/methods MH - Receptor Protein-Tyrosine Kinases/metabolism MH - Receptors, Cholinergic/*drug effects/immunology/metabolism/physiology MH - Rhabdomyosarcoma EDAT- 2005/04/19 09:00 MHDA- 2005/07/06 09:00 CRDT- 2005/04/19 09:00 PHST- 2004/08/20 00:00 [received] PHST- 2004/10/26 00:00 [revised] PHST- 2005/01/06 00:00 [accepted] PHST- 2005/04/19 09:00 [pubmed] PHST- 2005/07/06 09:00 [medline] PHST- 2005/04/19 09:00 [entrez] AID - S0165-5728(05)00014-7 [pii] AID - 10.1016/j.jneuroim.2005.01.009 [doi] PST - ppublish SO - J Neuroimmunol. 2005 May;162(1-2):149-56. doi: 10.1016/j.jneuroim.2005.01.009.