Defining autoimmune aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Myalgic Encephalomyelitis (ME) is a multifactorial disorder affecting the nervous system that is defined by symptom-specific criteria and characterised by severe and prolonged fatigue. The aetiology of the disorder is unknown. Alterations in the innate and adaptive immune system, recurrent or persistent infections that can originate in the gut, autoantibody production and the effectiveness of B cell depletion (Rituximab) therapy suggest that ME patients may suffer from autoimmune responses.
The project benefits from collaborations with Prof Angela Vincent's Neuroimmunology group at Oxford University and with Prof Jo Cambridge's group at University College London that undertakes clinical trials of B-cell depletion for autoimmune disease.
The aim of this PhD project is to test the hypothesis that ME is an autoimmune disorder originating in the gut as a consequence of altered intestinal permeability (leaky gut) leading to exposure of the immune system to commensal gut microbes and their products and the generation of pathogenic (auto) antibodies cross-reactive with antigens expressed in the central nervous system (CNS). Using samples collected from ME patients with mild, moderate and severe symptoms the student will undertake the following objectives:
1. Investigate the presence of (auto) antibodies reactive with intestinal microbes and/or cells of the CNS using novel high throughput liquid and solid phase assays and immunohistochemical assays with tissue and primary neuronal cells, respectively.
2. Determine the presence and characteristics of T lymphocytes with the capacity to home to the CNS using multiparameter flow cytometry and cell-culture based functional assays.
3. Determine the impact of Rituximab therapy on (auto) antibodies reactive with intestinal microbes and/or CNS cells, and brain-homing T cells.
This multidisciplinary project provides an opportunity for extensive training in cell and molecular immunology and microbiology available within the groups of Profs Carding and Wileman at the UEA-Norwich Medical School.
Funding is via Invest in ME Research and UEA.