B-CELL RESEARCH/UK RITUXIMAB CLINICAL TRIAL
B LYMPHOCYTE SUBSET ANALYSIS IN PATIENTS WITH CHRONIC FATIGUE SYNDROME
Introduction
A preliminary B-cell study was designed to confirm and extend the earlier work of Dr Amolak Bansal [1]
on B-cells but using a different cohort of ME patients.
Our advisor Professor Edwards believed this was a useful study in
its own right and a pre-requisite for the rituximab clinical trial.
The Team
The Research Team Centre for Rheumatology
The group focuses its interests on B cell depletion (an idea introduced (with the now retired Professor Jo Edwards) approximately 10 years ago for the treatment of rheumatoid arthritis), exploring more precisely how the technique works and trying to explain the marked variation in response between different patients.
Epsom and St Helier University Hospitals NHS Trust,Surrey, UK
Dr. Bansal trained in immunology and allergy from 1989 to 1993 at St. Mary's Hospital in Manchester and at Hope Hospital in Salford. From here he spent five years (1993-1997) as Senior Lecturer and Consultant in Clinical Immunology in the Department of Medicine at the Princess Alexandra Hospital in Brisbane, Australia. From 1997 to the present date Dr. Bansal has worked as a Consultant in Clinical Immunology and Immunopathology at Epsom and St Helier University Hospital. Dr Bansal's key interests lie in allergy, autoimmunity, ME/CFS and immunodeficiency. Dr Bansal is also involved in the IiME funded gut microbiota study at IFR/UEA, and a neural antigen study on ME at IFR/Oxford.
Project Description
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is aheterogeneous condition of unknown aetiology characterized by
multiplesymptoms including fatigue, post-exertional malaise and cognitiveimpairment, lasting for at least 6 months.
Recently, two clinical trials of Bcell depletion therapy with rituximab (anti-CD20) reported convincingimprovement in symptoms.
A possible but undefined role for B cells hastherefore been proposed. Studies of the relative percentages of B cell subsetsin patients with
ME/CFS have not revealed any reproducible differencesfrom healthy controls (HC). In order to explore whether more subtlealterations in
B cell subsets related to B cell differentiation exist in ME/CFSpatients we used flow cytometry to immunophenotype CD191B cells.
The
panel utilized immunoglobulin (Ig)D, CD27 and CD38 (classical B cellsubsets) together with additional markers.
A total of 38 patients fulfillingCanadian, Centre for Disease Control and Fukuda ME/CFS criteria and 32age- and sex-matched HC were included. We found no difference inpercentages of classical subsets between ME/CFS patients and HC.
However, we observed an increase in frequency (P < 001) and expression (MFI;P 5 003) of CD24 on total B cells, confined to IgD1subsets.
Within memory subsets, a higher frequency of CD211CD38–B cells (>20%) was associated with the presence of ME/CFS
[odds ratio: 347 (115–1046);P 5 003] compared with HC, and there was a negative correlation with disease duration.
In conclusion, we identified possible changes in B cellphenotype in patients with ME/CFS.
These may reflect altered B cellfunction and, if confirmed in other patient cohorts, could provide aplatform for studies based on clinical course or responsiveness to rituximabtherapy.
Peer reviewing of this study was performed in March 2014.
The paper from this study was published here - http://onlinelibrary.wiley.com/doi/10.1111/cei.12749/abstract
See also http://www.investinme.org/ce-news-1603-01.shtml
Funding
Funding is via Invest in ME Research.