B-CELL RESEARCH/UK RITUXIMAB CLINICAL TRIAL
The potential role of B cells and their products in ME/CFS Patients
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous disease of unknown aetiology and pathogenesis. There is no therapeutic strategy available for patients with this diagnosis apart from psychological support and graded exercise therapy. Support for both is controversial.
Recently an imaging study found distinct diminished white matter and white matter abnormalities in the right hemisphere of the brain in ME/CFS patients compared with age and sex matched healthy controls, supporting a biomedical cause for an as yet undiscovered pathogenic process in ME/CFS patients [1,2]. The majority of patients with ME/CFS describe a viral infection prior to onset . However the absence of any concrete evidence for persistent viral infection and the wide range of physical, neurocognitive and autonomic symptoms described by ME/CFS patients suggest that this may represent a precipitating factor for the changes in neurological function associated with this condition.
Dr G. Cambridge Group (UCL; Rheumatology Department): Dr Cambridge and her group at UCL have outstanding expertise in B cell biology and pioneered the use of Rituximab for autoimmune diseases.
Dr Amolak Bansal (St Helier University Hospitals, NHS Trust): Consultant Immunologist: Dr Bansal has an extensive, well described cohort of patients with ME/CFS and an established and well-recognised research platform.
Fane Mensah (currently employed at UCL): An astute, highly motivated and determined young scientist, who holds a master in Infection and Immunity. Fane has shown to perform high quality research resulted in publications during his Bachelor and Master studies. Fane has already performed really promising research on B cell phenotype in ME/CFS patients, which we propose to extend with the expertise of Dr. Cambridge and the clinical and immunological insight in ME/CFS by Drs. Bansal and Drs. Berkovitz. We will also seek to collaborate with Research groups who share a similar interest in ME/CFS immunology and of Invest ME Research.
Recent studies have identified abnormalities in the blood of patients, which have strengthened
the suspicion that the immune system contributes to ME/CFS. Changes in populations of white blood
cells, called B cells, in ME/CFS have been reported by several research groups including those in
the UK (Dr Bansal, St Helier Hospital).
In addition, treatment with anti-B cell therapy using Rituximab by Fluge and colleagues in Norway have shown benefit to ME patients.
At UCL, with our extensive experience of B cell depletion therapy with rituximab we are performing a promising and extended B cell specific characterization, highlighting certain B cell subsets within ME/CFS patients. These B cells may also play an important role in disease progression.
Our hypothesis is that certain B cell products (antibodies and soluble factors) may be involved in ME/CFS. This may be the result of a number of different initial ‘trigger’, particularly virus infection (e.g. glandular fever).
We will therefore investigate:
- Relative distribution of different maturation stages of B cells
- How B cells function in response to specific stimuli in culture
- Possible B cell related targets for intervention strategies
Funding is via Invest in ME Research.
How Does This Align With IiME Objectives/What is the Justification for Project
Based on a small clinical trial of ME/CFS patients, B cell depletion therapy with Rituximab has provided a focus for both laboratory-based research and supplied some hope for patients suffering from ME/CFS. It is therefore of enormous clinical importance to identify the possible pathways of Immune cell (B and T cells) involvement in ME/CFS so that we can identify patients who will most likely benefit from a particular therapeutic intervention. As there are no obvious inflammatory or other biomarkers for ME/CFS, we a using a stratification-based approach to investigate both B cell function and the possible consequences of a virus infection or other insult on physiological and immune parameters. This work is vital to the success of any clinical trial or other treatment approach, given the heterogeneity of the condition. The aim of IiMER is to bring forward a logical basis for treatment of ME based on ‘solid’ biomedical-based research and this project fulfills that brief.