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TG6 autoimmunity and the development of neurological dysfunction in gluten sensitivity related disorders

Project Description

The Sheffield Institute of Gluten Related Disorders (SiGRED) has an international reputation in the field of Coeliac Disease (CD) and the neurological manifestations of gluten related disorders (GRD). Work done at SiGRED was responsible for the identification, characterisation and clinical management of the neurological manifestations of GRD. Amongst many major achievements was the identification of transglutaminase 6 (TG6) as a potential target antigen in gluten sensitivity related neurological dysfunction and the potential use of TG6 auto-antibodies as a diagnostic biomarker for the neurological manifestations of GRD.

This project aims to investigate the pathophysiology of neurological dysfunction in GRD with a particular emphasis on TG6 autoimmunity.

The primary aims are:
1 Determining if B cells/plasma cells found in the gut of patients with GRD are fully differentiated IgA secreting plasma cells and if immunoglobulin produced by these cells is specific to TG6
2 Determining if such plasma cells and corresponding antibodies against TG6 and other gluten-related antibodies are present in the cerebrospinal fluid of patients with gluten ataxia
3 Histological characterization of blood-brain barrier (BBB) dysfunction and IgA deposition against TG6 using brain tissue from patients with GRD

The project will be jointly supervised by Paul Heath, Senior Scientific Officer, SITRaN, Julie Simpson, Lecturer in Translational Neuropathology, SITRaN and Professor Marios Hadjivassiliou, Consulatnt Neurologist

Funding Notes

This funding from Neurocare and Ryder-Briggs charitable organisation covers Home fee and RCUK rate stipend for three years.

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