{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T22:37:51Z","timestamp":1784673471043,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:p>\n                    Graves\u2019 disease is an autoimmune disorder, which is characterized by stimulatory antibodies targeting the human thyrotropin receptor (TSHR), resulting in hyperthyroidism and multiple organ damage. We systematically investigated monomeric and dimeric fusion proteins of the A subunit of TSHR for efficacy to bind to the monoclonal patient antibody M22, to interact with Graves\u2019 patient serum samples, and to impact on anti-TSHR antibody titers, hyperthyroidism, tachycardia and other\n                    <jats:italic>in vivo<\/jats:italic>\n                    read-outs in a long-term mouse model of Graves\u2019 disease induced by immunization with a recombinant adenovirus encoding TSHR A. Binding assays and functional measurements of TSHR-dependent cAMP formation showed binding of monomeric TSHR-His and dimeric TSHR-Fc to the anti-TSHR antibody M22 at low-effective concentrations (EC\n                    <jats:sub>50<\/jats:sub>\n                    of 5.7 nmol\/L and 8.6 nmol\/L) and inhibition of the effects of this antibody at high efficiencies (IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 16\u201320 nmol\/L). Both proteins also block the effects of polyclonal anti-TSHR antibodies occurring in Graves\u2019 patient sera with somewhat lower average efficiencies (mean IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 29 nmol\/L and 68 nmol\/L). However,\n                    <jats:italic>in vivo<\/jats:italic>\n                    characterization of epicutaneous patch administrations of TSHR-Fc at doses of 0.3 and 0.6 mg\/kg body weight in a murine Graves\u2019 disease model did not result in any improvement of disease parameters. In conclusion, high affinity binding of TSHR-Fc to pathological anti-TSHR antibodies was not matched by efficacy to improve Graves\u2019 disease parameter in a long-term mouse model.\n                  <\/jats:p>","DOI":"10.1530\/joe-20-0061","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T13:51:12Z","timestamp":1590069072000},"page":"135-147","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":8,"title":["Thyroid-stimulating hormone receptor (TSHR) fusion proteins in Graves\u2019 disease"],"prefix":"10.1530","volume":"246","author":[{"given":"Hans-Peter","family":"Holthoff","sequence":"first","affiliation":[{"name":"1Procorde \u2013 advancecor, Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Uhland","sequence":"additional","affiliation":[{"name":"1Procorde \u2013 advancecor, Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor","family":"Laszlo Kovacs","sequence":"additional","affiliation":[{"name":"21st Department of Internal Medicine, Flor Ferenc Hospital, Kistarcsa, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Reimann","sequence":"additional","affiliation":[{"name":"1Procorde \u2013 advancecor, Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Adler","sequence":"additional","affiliation":[{"name":"1Procorde \u2013 advancecor, Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Wenhart","sequence":"additional","affiliation":[{"name":"1Procorde \u2013 advancecor, Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ungerer","sequence":"additional","affiliation":[{"name":"1Procorde \u2013 advancecor, Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/246\/2\/JOE-20-0061.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/246\/2\/JOE-20-0061.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:57:09Z","timestamp":1784555829000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/246\/2\/135-147\/5297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/joe-20-0061","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8]]}}}