UK Rituximab Paper

Seanko

Well-Known Member
The team behind the UK Rituximab trial at University College London (UCL) have published their first paper in the Journal of Transactional Immunology. The study is being funded by the charity Invest in ME (IiME)

[bimg=300|no-lightbox]https://upload.wikimedia.org/wikipedia/commons/thumb/d/d0/Rituximab.png/300px-Rituximab.png[/bimg]
Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study

F. Mensah1, A. Bansal2, S. Berkovitz3,A. Sharma1,V. Reddy1,M. J. Leandro1and G. Cambridge1
Keywords:

B cells; chronic fatigue syndrome; flow cytometry; human; myalgic encephalomyelitis

Summary

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous condition of unknown aetiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months. Recently, two clinical trials of B cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms.


A possible but undefined role for B cells has therefore been proposed. Studies of the relative percentages of B cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC). In order to explore whether more subtle alterations in B cell subsets related to B cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19+ B cells.

The panel utilized immunoglobulin (Ig)D, CD27 and CD38 (classical B cell subsets) together with additional markers. A total of 38 patients fulfilling Canadian, Centre for Disease Control and Fukuda ME/CFS criteria and 32 age- and sex-matched HC were included. We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (P < 0·01) and expression (MFI;P = 0·03) of CD24 on total B cells, confined to IgD+ subsets. Within memory subsets, a higher frequency of CD21+CD38– B cells (>20%) was associated with the presence of ME/CFS [odds ratio: 3·47 (1·15–10·46); P = 0·03] compared with HC, and there was a negative correlation with disease duration.

In conclusion, we identified possible changes in B cell phenotype in patients with ME/CFS. These may reflect altered B cell function and, if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab therapy.
 
Last edited:

Cort

Founder of Health Rising and Phoenix Rising
Staff member
The team behind the UK Rituximab trial at University College London (UCL) have published their first paper in the Journal of Transactional Immunology. The study is being funded by the charity Invest in ME (IiME)

[bimg=300|no-lightbox]https://upload.wikimedia.org/wikipedia/commons/thumb/d/d0/Rituximab.png/300px-Rituximab.png[/bimg]
Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study

F. Mensah1, A. Bansal2, S. Berkovitz3,A. Sharma1,V. Reddy1,M. J. Leandro1and G. Cambridge1
Keywords:

B cells; chronic fatigue syndrome; flow cytometry; human; myalgic encephalomyelitis

Summary

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous condition of unknown aetiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months. Recently, two clinical trials of B cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms.


A possible but undefined role for B cells has therefore been proposed. Studies of the relative percentages of B cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC). In order to explore whether more subtle alterations in B cell subsets related to B cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19+ B cells.

The panel utilized immunoglobulin (Ig)D, CD27 and CD38 (classical B cell subsets) together with additional markers. A total of 38 patients fulfilling Canadian, Centre for Disease Control and Fukuda ME/CFS criteria and 32 age- and sex-matched HC were included. We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (P < 0·01) and expression (MFI;P = 0·03) of CD24 on total B cells, confined to IgD+ subsets. Within memory subsets, a higher frequency of CD21+CD38– B cells (>20%) was associated with the presence of ME/CFS [odds ratio: 3·47 (1·15–10·46); P = 0·03] compared with HC, and there was a negative correlation with disease duration.

In conclusion, we identified possible changes in B cell phenotype in patients with ME/CFS. These may reflect altered B cell function and, if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab therapy.
I think that it was good that they found increased frequency and expression of that receptor on B-cells. This isn't going to be easy to understand, obviously.
 

Seanko

Well-Known Member
Researcher funders Invest in ME have produced a layman's guide to the paper.
Laymen's guide to Paper

"The initial aim of our studies was to investigate whether there was any difference between surface markers expressed on B cells from patients with ME/CFS and those from age and sex matched healthy controls.

We looked at the % cells positive and also the number of markers per B cell, of 18 different markers expressed on B cells.

As you are aware, promising results have been reported from Norway in 2 earlier B cell depletion (Rituximab) trials and we are investigating many aspects of B cell function which may indicate, firstly, why Rituximab seems to work and to also identify patients most likely to benefit from this or related therapies.

In our study we have found no significant differences between the 10 traditional B cell subsets of ME/CFS patients compared to those from controls.
We then added in additional markers in order to further extend this characterization.

Here we did find an increase in a molecule expressed on ‘new’ B cells, that is the ones most recently exiting the bone marrow.
This is a differentiation marker called CD24.

CD24 polymorphisms (genetic changes) have also been described in different autoimmune diseases.

CD24 is a cell ‘adhesion’ molecule which is involved in the way B cells interact with other cells and with their surroundings.

This marker is important in the early stages of B cell maturation, where it is also at its highest expression and it is where we have found the differences.

We have also found another B cell phenotype which may be related in a negative way with disease duration.

We hope to extend these studies to other ME/CFS cohorts in other centers.

We will now continue to investigate the functional consequences of these changes in CD24 expression to get a better picture of what these findings may mean in relation to ME/CFS symptoms and in relation to what is found following Rituximab therapy.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
Researcher funders Invest in ME have produced a layman's guide to the paper.
Laymen's guide to Paper

"The initial aim of our studies was to investigate whether there was any difference between surface markers expressed on B cells from patients with ME/CFS and those from age and sex matched healthy controls.

We looked at the % cells positive and also the number of markers per B cell, of 18 different markers expressed on B cells.

As you are aware, promising results have been reported from Norway in 2 earlier B cell depletion (Rituximab) trials and we are investigating many aspects of B cell function which may indicate, firstly, why Rituximab seems to work and to also identify patients most likely to benefit from this or related therapies.

In our study we have found no significant differences between the 10 traditional B cell subsets of ME/CFS patients compared to those from controls.
We then added in additional markers in order to further extend this characterization.

Here we did find an increase in a molecule expressed on ‘new’ B cells, that is the ones most recently exiting the bone marrow.
This is a differentiation marker called CD24.

CD24 polymorphisms (genetic changes) have also been described in different autoimmune diseases.

CD24 is a cell ‘adhesion’ molecule which is involved in the way B cells interact with other cells and with their surroundings.

This marker is important in the early stages of B cell maturation, where it is also at its highest expression and it is where we have found the differences.

We have also found another B cell phenotype which may be related in a negative way with disease duration.

We hope to extend these studies to other ME/CFS cohorts in other centers.

We will now continue to investigate the functional consequences of these changes in CD24 expression to get a better picture of what these findings may mean in relation to ME/CFS symptoms and in relation to what is found following Rituximab therapy.
Anyone want to do a blog on this? (Please :shy: ...I will help!)
 

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