Searchable abstracts of presentations at key conferences in endocrinology

ea0084op-04-21 | Oral Session 4: Basic 1 | ETA2022

CRYO-electron microscopy structures of human thyroid peroxidase (TPO) in complex with tpo antibodies

Baker Stuart , Nunez Miguel Ricardo , Thomas Daniel , Powell Michael , Furmaniak Jadwiga , Rees Smith Bernard

Objectives: Thyroid peroxidase (TPO) is a key enzyme in the synthesis of thyroid hormones and is a target for autoimmune responses in autoimmune thyroid disease. TPO autoantibody (TPOAb) binding epitopes have been mapped on the peroxidase domain (POD) and the complement control protein like domain (CCP). This study aimed to solve the molecular structures of TPO bound to TPO antibodies.Methods: An extracellular domain (ECD) of human TPO (amino acids; aa 1...

ea0084ps3-12-109 | Graves’ Disease 2 and Orbitopathy | ETA2022

Blocking the TSH receptor with human monoclonal autoantibody K1-70TM in patients with graves’ disease – results from a phase 1 clinical trial

Furmaniak Jadwiga , Sanders Jane , Sanders Paul , Li Yang , Rees Smith Bernard

Objectives: TSH receptor (TSHR) autoantibodies (TRAb) which mimic the actions of TSH are responsible for hyperthyroidism in Graves’ disease (GD) which is often associated with Graves’ orbitopathy (GO). K1-70 is a TSHR specific human monoclonal autoantibody which binds to the TSHR with high affinity and prevents stimulation of the TSHR by TSH and TRAb. Safety, tolerability, pharmacokinetic, pharmocodynamic and immunogenic effects of K1-70 in patients with GD were asse...

ea0028oc3.5 | Obesity, thyroid and Addison's disease | SFEBES2012

Steroidogenic function following B lymphocyte depletion therapy in new onset autoimmune Addison’s disease

Pearce Simon , Mitchell Anna , Bennett Stuart , King Philip , Chandran Sukesh , Nag Sath , Chen Shu , Furmaniak Jadwiga , Isaacs John , Vaidya Bijay

Background: A diagnosis of Addison’s disease means lifelong dependence on daily glucocorticoid and mineralocorticoid therapy and is associated with increased morbidity and mortality, as well as a risk of unexpected adrenal crisis. We wished to explore whether immunomodulatory therapy at an early stage of autoimmune Addison’s disease could lead to preservation or improvement in adrenal steroidogenic function.Design: We conducted an open-label, p...

ea0084op-01-01 | Oral Session 1: Topic Highlights | ETA2022

Cryo-electron microscopy structure of full length TSH receptor in complex with TSH receptor blocking human monoclonal autoantibody K1-70TM

Nunez Miguel Ricardo , Sanders Paul , Allen Lloyd , Evans Michele , Holly Matthew , Johnson William , Sullivan Andrew , Miller-Gallacher Jennifer , Sanders Jane , Furmaniak Jadwiga , Rees Smith Bernard

Objectives: The crystal structures of the TSH receptor (TSHR) leucine rich repeat domain (LRD) bound to TSHR stimulating monoclonal autoantibody M22TM or to TSHR blocking monoclonal autoantibody K1-70TM and antibody free have been solved previously. Cryo-electron microscopy (cryo-EM) was now used to solve the structure of full length TSHR in complex with K1-70TM.Methods: Recombinant human TSHR expressed in CHO cells was i...

ea0031p333 | Steroids | SFEBES2013

Revival of adrenal function in established autoimmune Addison's disease

Gan Earn H , Mitchell Anna L , Perros Petros , James Andy , Ball Steve , Furmaniak Jadwiga , Chen Shu , Quinton Richard , Pearce Simon HS

Despite lifelong glucocorticoid and mineralocorticoid replacement, there is excess morbidity and mortality associated with autoimmune Addison’s disease (AAD). Adrenal cortical cells undergo continuous self-renewal from a population of subcapsular progenitor or stem cells, under the influence of ACTH. We aimed to determine if synthetic ACTH analogue could revive adrenal steroidogenic function and ameliorate AAD.We performed an open-label trial of syn...