1. Correlations were determined for end-of-study results in TSHR-immunised mice.

A study on
plasmid-induced TSHR immunisation found reasonable correlations between thyroxin T4
value and anti-TSHR antibody titres . Also, after Ad-TSHR immunisation, we found high
correlations coefficients >0.7 for thyroid sizes vs. thyroxin (T4) levels, vs. anti-TSHR titre
levels and vs. heart weights and heart rates at the end of the observation period . In contrast,
thyroid sizes did not correlateas well with the absolute cAMP-stimulatory capacities of the
anti-TSHR antibodies on test cells, which were generally not well correlated to the other
parameters.These findings indicate that the animal model is consistently characterised by
generation of specific anti-TSHR antibodies whose levels in single animals impact on the
amount of thyroid enlargement and on serum T4 levels as well as on the cardiac consequences
of disease.We also conclude from these data that effects of anti-TSHR antibodies on target
cells different from cAMP stimulation should be relevant, because the biological effect of
these antibodies is not precisely predicted just by measuring their capacity to stimulate cAMP
levels in test cells. Such alternative second messenger systems could.
Korelasi bertekad untuk hasil akhir dari studi pada tikus diimunisasi TSHR. Sebuah
studi plasmid-diinduksi vaksin TSHR kembali menemukan korelasi yang wajar antara nilai
thyroxin T4 dan anti-TSHR antibodi titres. Juga, setelah imunisasi Ad-TSHR, kami
menemukan korelasi tinggi koefisien > 0.7 untuk ukuran tiroid vs thyroxin (T4) tingkat, vs
anti-TSHR titre tingkat dan vs beban jantung dan detak jantung pada akhir periode
pengamatan. Sebaliknya, ukuran tiroid tidak tidak berhubungan baik dengan kapasitas kamp-
stimulasi mutlak antibodi anti-TSHR pada tes sel, yang yang umumnya tidak baik berkorelasi
dengan parameter lain. Temuan ini menunjukkan bahwa hewan model yang konsisten
ditandai dengan generasi antibodi spesifik anti-TSHR yang tingkat satu hewan dampak pada
jumlah tiroid pembesaran dan pada kadar serum T4 serta akibat penyakit jantung. Kami juga
menyimpulkan dari data tersebut bahwa efek anti-TSHR antibodi pada menargetkan sel...
2. Various approaches have been used to model human Graves’ disease in mice, including
transfected fibroblasts, and plasmid or adenoviral immunisations with the extracellularA
subunit of the human thyrotropin receptor (TSHR). Some of these models were only observed
for a short time period or were self-limiting. A long-term model for human Graves’ disease
was established in mice using continuing immunisations (4-weekly injections) with
recombinant adenovirus expressing TSHR. Generation of TSHR binding cAMPstimulatory
antibodies, thyroid enlargement and alterations, elevated serumthyroxin levels, tachycardia
and cardiac hypertrophy were maintained for at least 9 months in all Ad-TSHRimmunised
mice. Here, we show that these mice suffer from orbitopathy, which was detected by serial
orbital sectioning and histomorphometry. Attempts to treat established Graves’ disease in
preclinical mouse model studies have included small molecule allosteric antagonists and
specific antagonist antibodies which were isolated from hypothyroid patients. In addition,
novel peptides have been conceived which mimic the cylindrical loops of the TSHR leucine-
rich repeat domain, in order to re-establish tolerance toward the antigen. Here, we show
preliminary results that one set of these peptides improves or even cures all signs and
symptoms of Graves’ disease in mice after six consecutive monthly injections. First beneficial
effects were observed 3–4 months after starting these therapies. In immunologically naïve
mice, administration of the peptides did not induce any immune response.
berbagai pendekatan telah digunakan untuk model kuburan ' penyakit manusia pada
tikus, termasuk transfected fibroblas, dan plasmid atau adenoviral imunisasi dengan
extracellularA subunit reseptor manusia thyrotropin (TSHR). Beberapa model ini diamati
hanya untuk jangka waktu singkat atau yang membatasi diri. Model jangka panjang untuk
penyakit manusia kuburan ' didirikan dengan tikus menggunakan terus imunisasi (4-mingguan
suntikan) dengan adenovirus rekombinan mengekspresikan TSHR. Generasi TSHR mengikat
cAMPstimulatory antibodi, pembesaran tiroid dan perubahan, serumthyroxin ditinggikan
tingkat, takikardia dan jantung hipertrofi tetap dipertahankan selama sedikitnya 9 bulan dalam
semua iklan-TSHRimmunised tikus. Di sini, kami menunjukkan bahwa tikus tersebut
menderita dari orbitopathy, yang terdeteksi oleh-sectioning orbit serial dan
histomorphometry. Upaya untuk mengobati didirikan kuburan ' penyakit dalam studi model
tikus praklinis termasuk molekul kecil alosterik antagonis dan spesifik antagonis antibodi