{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T11:50:16Z","timestamp":1779277816519,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,10,13]],"date-time":"2009-10-13T00:00:00Z","timestamp":1255392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Myasthenia gravis (MG) and its animal model, experimental autoimmune myasthenia gravis (EAMG), are antibody (Ab)\u2010mediated autoimmune diseases, in which autoantibodies bind to and cause loss of muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. To develop a specific immunotherapy of MG, we treated rats with ongoing EAMG by intraperitoneal injection of bacterially\u2010expressed human muscle AChR constructs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rats with ongoing EAMG received intraperitoneal treatment with the constructs weekly for 5 weeks beginning after the acute phase. Autoantibody concentration, subclassification, and specificity were analyzed to address the underlying therapeutic mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EAMG was specifically suppressed by diverting autoantibody production away from pathologically relevant specificities directed at epitopes on the extracellular surface of muscle AChRs toward pathologically irrelevant epitopes on the cytoplasmic domain. A mixture of subunit cytoplasmic domains was more effective than a mixture containing both extracellular and cytoplasmic domains or than only the extracellular domain of \u03b11 subunits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Therapy using only cytoplasmic domains, which lack pathologically relevant epitopes, avoids the potential liability of boosting the pathological response. Use of a mixture of bacterially\u2010expressed human muscle AChR cytoplasmic domains for antigen\u2010specific immunosuppression of myasthenia gravis has the potential to be specific, robust, and safe. ANN NEUROL 2010;67:441\u2013451<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.21901","type":"journal-article","created":{"date-parts":[[2009,10,14]],"date-time":"2009-10-14T00:33:39Z","timestamp":1255480419000},"page":"441-451","source":"Crossref","is-referenced-by-count":20,"title":["Specific immunotherapy of experimental myasthenia gravis by a novel mechanism"],"prefix":"10.1002","volume":"67","author":[{"given":"Jie","family":"Luo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Kuryatov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon M.","family":"Lindstrom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,4,26]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29894"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(200004)23:4<453::AID-MUS3>3.0.CO;2-O"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)05186-2"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.180.4088.871"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2008"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1998.tb01190.x"},{"key":"e_1_2_7_8_2","article-title":"Main immunogenic region structure promotes binding of conformation\u2010dependent myasthenia gravis autoantibodies, nicotinic acetylcholine receptor conformation maturation, and agonist sensitivity","author":"Luo J","journal-title":"J Neurosci"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.1.188"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90037-3"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00520a016"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20030"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-829593"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.8.4006"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1996.0209"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(97)01171-7"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.48.1.341"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1997.4432"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.14.8086"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1996.tb21134.x"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119857"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb10910.x"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(94)00187-S"},{"key":"e_1_2_7_24_2","doi-asserted-by":"crossref","first-page":"5757","DOI":"10.4049\/jimmunol.162.10.5757","article-title":"Mechanisms of nasal tolerance induction in experimental autoimmune myasthenia gravis: identification of regulatory cells","volume":"162","author":"Shi FD","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(94)00235-G"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2004.04.010"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.7.3599"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1405.007"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1976.tb47691.x"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1976.tb47693.x"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(93)90237-F"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181a41211"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2008.08.264"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.2165\/00063030-200216030-00003"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8121"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1998.00521.x"},{"key":"e_1_2_7_37_2","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.4049\/jimmunol.146.7.2245","article-title":"Recombinant human acetylcholine receptor \u03b1\u2010subunit induces chronic experimental autoimmune myasthenia gravis","volume":"146","author":"Lennon VA","year":"1991","journal-title":"J Immunol"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.2.769"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00846.x"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830230816"},{"key":"e_1_2_7_41_2","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.4049\/jimmunol.161.6.2856","article-title":"The Th2 cytokine IL\u20104 is not required for the progression of antibody\u2010dependent autoimmune myasthenia gravis","volume":"161","author":"Balasa B","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(99)01553-4"},{"key":"e_1_2_7_43_2","doi-asserted-by":"crossref","first-page":"7189","DOI":"10.4049\/jimmunol.162.12.7189","article-title":"Experimental autoimmune myasthenia gravis may occur in the context of a polarized Th1\u2010or Th2\u2010type immune response in rats","volume":"162","author":"Saoudi A","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.4.728"},{"key":"e_1_2_7_45_2","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.4049\/jimmunol.153.7.3353","article-title":"Idiotype\u2010and anti\u2010idiotype\u2010reactive T lymphocytes in myasthenia gravis. Evidence for the involvement of different subpopulations of T helper lymphocytes","volume":"153","author":"Yi Q","year":"1994","journal-title":"J Immunol"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1254.033"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(78)90052-4"},{"key":"e_1_2_7_48_2","doi-asserted-by":"crossref","first-page":"234","DOI":"10.4049\/jimmunol.135.1.234","article-title":"Monoclonal anti\u2010acetylcholine receptor antibodies with differing capacities to induce experimental autoimmune myasthenia gravis","volume":"135","author":"Gomez CM","year":"1985","journal-title":"J Immunol"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(87)90092-0"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.21901","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.21901","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T15:37:05Z","timestamp":1697470625000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.21901"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4]]},"references-count":48,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2010,4]]}},"alternative-id":["10.1002\/ana.21901"],"URL":"https:\/\/doi.org\/10.1002\/ana.21901","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4]]}}}