Immune manipulation for Graves' disease: Re-exploring an unfulfilled promise with modern translational research

Although Graves' disease is the commonest autoimmune thyroid disorder, current therapeutics typically center on the eradication of the antigenic stimulus (i.e. thyroid gland) rather than radically tackling the underlying autoimmune processes. Consequently, it is not a surprising fact that Graves' disease remains essentially a chronic drug-dependent ailment afflicting untold numbers worldwide for decades despite progress in deciphering its autoimmune nature. Addressing the latter is key to a future cure as underscored by appropriate, albeit crude, proof-of-concept scenarios of clinical remissions achieved with hematopoietic stem cell transplantation, immune down-regulation during pregnancy, use of corticosteroids or immunosuppressives, and cytokine biologics in animal models. Ongoing basic and translational research to further elucidate and refine our understanding of the pathogenesis of Graves' disease holds the promise of unraveling novel immune manipulative techniques that will bring the world a step closer to the elusive cure of the underlying autoimmunity amidst skepticisms on the value of the science from the present lack of paralleled advances at the bedside. We review the updated literature and describe the forms of immune manipulation hitherto explored that will offer a route to a future cure, from thionamides, hematopoietic stem cell transplantation to the latest immunomodulatory agents.