Endocrine Abstracts

Graves’ disease is characterised by an autoimmune response to the TSH receptor leading to circulating stimulatory TSH receptor antibodies (TRAbs) which directly cause hyperthyroidism and goitre. Patients with thyroid eye disease, children and teenagers, and those with large goitre, severe hyperthyroidism or high TRAb titres have unmet clinical needs and frequently have unsatisfactory outcomes with current therapies. In common with all other antibodies, TRAbs are secreted from terminally differentiated B lymphocytes, plasma cells, which may reside in the thyroid, lymphoid tissues and bone marrow, and from circulating plasmablasts. Once long-lived TRAb-secreting plasma cells become established in a bone marrow niche, it is likely that Graves’ disease becomes intractable and definitive therapy is necessary. B lymphocyte and plasma cell immunotherapies, with different cell depleting and cytokine modulating activities appear to have additional efficacy on top of antithyroid drugs, and recent trials of these agents will be reviewed. In addition, other novel approaches including antigen-specific immunotherapies will be discussed. A better understanding of the immunopathogenesis of Graves’ disease will allow stratification of particular patient groups to more aggressive therapies in the future.