Background
Anti-transglutaminase 6 antibodies (anti- TG6) have been described and studied by our group in collaboration with Professor Aeschlimann at Cardiff University. They are highly prevalent in patients with gluten ataxia and we have previously published that they are associated with cerebellar atrophy but also with thalamic atrophy.
Gluten responsive headaches, which have been termed gluten encephalopathy, are well recognised in the context of gluten sensitivity. This condition is defined by its improvement with adherence to a strict gluten free diet. We have previously linked gluten encephalopathy with accelerated rates of white matter disease accumulation; white matter disease is known to predispose to dementia.
These headaches can exist alongside gluten ataxia and other manifestations of gluten sensitivity, but they can arise in isolation. What is currently unclear is how many patients with gluten responsive headaches are amongst those presenting to secondary care headache clinics.
Work Package 1
(i) Systematic review of the physiological and pathophysiological roles of transglutaminase 6 and anti-TG6 antibodies in health and disease.
(ii) Systematic review of headache in patients with gluten sensitivity
Work Package 2
Our group are currently investigating clinical, imaging and neuropsychological manifestations of gluten sensitivity over time, funded by Beyond Celiac (PI Hoggard) from the >1000 patients currently being cared for through the Sheffield Ataxia and Gluten sensitivity neurology clinics. Patients are being recruited for neuropsychological assessment and quality of life questionnaires. This sub-study will be to assess retrospective data from this larger on-going project. TG6 status is available for all participants.
Aims:
(i) Assess cardiovascular risk factors in patients, with and without anti-TG 6 antibodies, already under treatment for gluten sensitivity with gluten free diet- either alone or in combination with immunosuppression (in patients with gluten encephalopathy).
(ii) Investigate correlation between serology (anti-TG6) and neurophysiology for patients with gluten neuropathy (neuropathy being the 2nd commonest manifestation of gluten sensitivity).
Work Package 3
Prevalence of anti-TG6 antibodies in patients presenting to secondary care with headache. You will be embedded within a headache clinic at Sheffield Teaching Hospitals to facilitate recruitment to a prospective study to find the prevalence of anti TG 6, anti TG 2 and antigliadin antibodies in patients referred from primary care with headache.
Our previous work indicates that the general population prevalence of antigliadin antibodies is around 12%. If the null hypothesis is that there is no difference in prevalence between the headache population and the general population is accepted, a sample size of 163 will give 95% confidence and margin of error of 5%. This means over 2 years, assuming 40 working weeks per year, approximately 2 participants need to be recruited per week.
Aims
(i) Prospective study of the serological prevalence of antigliadin antibodies and TG6 antibodies in patients attending a secondary care headache clinic.
(ii) Describe, compare and contrast the clinical manifestations of headaches in those patients with antigliadin antibodies, those with TG6 antibodies, those with both and those patients with neither.
Entry Requirements:
Candidates must have a first or upper second-class honours degree or significant research experience.
How to apply:
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply
Please clearly state the prospective main supervisor in the respective box and select Neuroscience as the department.
Enquiries:
Interested candidates should in the first instance contact Professor Hadjivassiliou ([Email Address Removed])
Start date:
October 2023
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