Identifying the ‘Achilles heel’ of type 1 diabetes

Summary When Thetis dipped her son Achilles into the River Styx to make him immortal, she held him by the heel, which was not submerged, and thus created a weak spot that proved deadly for Achilles. Millennia later, Achilles heel is part of today’s lexicon meaning an area of weakness or a vulnerable spot that causes failure. Also implied is that an Achilles heel is often missed, forgotten or under‐appreciated until it is under attack, and then failure is fatal. Paris killed Achilles with an arrow ‘guided by the Gods’. Understanding the pathogenesis of type 1 diabetes (T1D) in order to direct therapy for prevention and treatment is a major goal of research into T1D. At the International Congress of the Immunology of Diabetes Society, 2018, five leading experts were asked to present the case for a particular cell/element that could represent ‘the Achilles heel of T1D’. These included neutrophils, B cells, CD8 + T cells, regulatory CD4 + T cells, and enteroviruses, all of which have been proposed to play an important role in the pathogenesis of type 1 diabetes. Did a single entity emerge as ‘the’ Achilles heel of T1D? The arguments are summarized here, to make this case.