Background & Purpose

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PURPOSE

A number of beta cell neoepitopes have been described and implicated in Type 1 Diabetes (T1D) pathogenesis. However, the role of neoepitopes in the breakdown of self-tolerance and their utility as biomarkers for improved disease staging remains unclear and their potential as possible therapeutic targets has not been determined. JDRF is soliciting EOIs to support research projects that explicitly address the role and utility of neoepitopes in T1D and facilitate novel findings into the clinic.

BACKGROUND

In several autoimmune diseases, neoepitope responses have been directly linked to the pathogenesis of the disease and have been successfully utilized as disease biomarkers. One such example is antibodies to citrullinated peptides for the diagnosis of rheumatoid arthritis. However, in T1D, incomplete understanding of the timing and prevalence of neoepitope generation and the immune responses to neoepitopes has limited the utility of neoepitopes for staging, stratification, or to inform therapeutic interventions. To date, multiple lines of evidence demonstrate that neoepitopes can be formed as a result of beta cell stress, metabolic stress, inflammation, and other situations. Both cellular and humoral responses to neoepitopes have been detected in individuals with and those in the early stages of T1D. Given that multiple neoepitopes have now been identified in T1D samples and work informing on their utility as biomarkers has commenced, this RFA prompts investigators to apply these findings to:

• Inform on the role of neoepitope responses in T1D to facilitate a mechanistic understanding of T1D.
• Develop and implement assays that improve on the current stratification and staging paradigms.
• Inform on existing or devise novel therapeutic approaches based on these responses.
• Capitalize on current advances in other fields to apply technologies and learnings to T1D.