TSHR-spe­cific lymph­o­cytes in Graves´ dis­ease patient blood

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TSHR-spe­cific lymph­o­cytes in Graves´ dis­ease patient blood

The devel­op­ment of innov­at­ive pep­tides that restore tol­er­ance to the anti­gen led to the improve­ment of all dis­ease symptoms.

Rel­ev­ant immune mech­an­isms which tar­get spe­cific (auto-)antigens have been iden­ti­fied using blood samples from Graves´ dis­ease (GD) patients, study­ing autoantibod­ies and immune cells. They allow to invest­ig­ate reg­u­lat­ory T cells and spe­cific anti­body responses, which are also observed in the clin­ic­ally well estab­lished spe­cific immune ther­apy of aller­gic diseases.
Innov­at­ive pep­tides have been con­ceived to treat GD – they mimic the cyl­indrical loops of the extra­cel­lu­lar A domain of the pivotal thyroid stim­u­lat­ing hor­mone receptor (TSHR). These pep­tides act as tol­er­iz­ing com­pounds, i. e. they re-estab­lish tol­er­ance towards the anti­gen. In long-term GD mod­els, they improved all dis­ease symp­toms after 2–3 monthly injec­tions. How­ever, they did not induce any immune response in naïve mice.
This thera­peutic concept has been fur­ther developed and expan­ded to treat other autoim­mune dis­eases, such as rheum­at­oid arth­ritis (RA), where ini­tial lead com­pounds have been iden­ti­fied in dis­ease models.

Degen H, Gav­vovidis J, Blanken­stein T, Uhland K, Ungerer M. TSHR-spe­cific lymph­o­cytes in Ad-TSHR-immun­ized nat­ive and HLA-DR3-trans­genic mice and in Graves´ dis­ease patient blood. Thyroid 2020, online preprint
doi: 10.1089/thy.2020.0338; https://doi.org/10.1089/thy.2020.0338