Work

Antibody-induced modulation of TSH receptor post-translational processing

Year: 2007

Type: article

Abstract: The post-translational processing of the TSH receptor (TSHR) includes intra-molecular cleavage with the loss of a 50 amino acid ectodomain region and the formation of two subunits (alpha and beta), followed by likely alpha subunit shedding. TSHR antibodies (TSHR-Abs), which are directed at the ectodomain, may influence thyroid function by stimulating or inhibiting TSHR signaling or may bind without any such influence (the neutral group of antibodies). When we examined the characteristics of a series of monoclonal TSHR-Abs, we found that many were able to inhibit receptor cleavage and enhance TSHR expression. This was especially apparent with the neutral type of TSHR-Abs directed to the cleaved region of the ectodomain (aa 316-366). Indeed, such inhibition appeared to be epitope dependent with TSHR-Abs directed to regions after residues 335-354 showing no such activity. We propose that this aberrant process, whereby TSHR-Abs influence antigen processing, is a novel mechanism for the maintenance and exacerbation of autoimmune thyroid disease.

Source: Journal of Endocrinology

DOI: 10.1677/joe-07-0058

Authors: Takao Ando, Rauf Latif, Terry F Davies

Institutions: Mount Sinai Hospital, James J. Peters VA Medical Center, Icahn School of Medicine at Mount Sinai

Language: English

Topic: Thyroid Disorders and Treatments

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases