B cell repopulation is not associated with disease activity

B

Disease can return following depletion with a B cell depleting agent. If you look at the blood you cant see who if going to get an attack or not. So is the B cell idea all wrong.

I think if a DMT is to work well it should have the capacity to physically or functionally deplete memory B cells. We have seen that they remain depleted for months, whereas B cell numbers return quicker. This report looks at early B cell repleters and concludes that disease activity can’t be related to this. So first point if you don’t focus in you won’t see anything and next point is you looking for a needle in a haystack and these are hidden by the others, so if you are looking for an orange top in a group of Liverpool (red) and Everton (blue) in a football crowd you have problem seeing the orange

With alemtuzumab this occurs within 3 months with rituximab it takes about longer but what returns isn’t the same and people don’t all relapse. I have come to terms with the belief that the blood is the wrong place to look. Drugs that work well clear the blood perhaps as a marker that they are clearing elsewhere. However disease can reactivate with very few cells in the blood.

This report looks at percentages but absolute numbers is key because if something goes up something else must go down, yet the cell number of the one of them could stay the same.

The cells that come back first are called immature or transitional cells and make looks of B cell growth factors like interleukin 10 which regulates T celld

Dorcet G, Migné H, Biotti D, Bost C, Lerebours F, Ciron J, Treiner E. Early B cells repopulation in multiple sclerosis patients treated with rituximab is not predictive of a risk of relapse or clinical progression. J Neurol. 2022:1-11. doi: 10.1007/s00415-022-11197-6. Online ahead of print.

Background: It is currently unknown whether early B cell reconstitution (EBR) in MS patients under rituximab is associated with a risk of relapse or progression.

Objectives: Analyzing EBR in rituximab-treated patients and its putative association with clinical findings.

Methods: Prospective lymphocytes immunophenotyping was performed in a monocentric cohort of MS patients treated by rituximab for 2 years. EBR was defined when B cells concentration was > 5 cells/mm3. B cell subsets were retrospectively associated with clinical data. Clinical and radiological monitoring included relapses, EDSS (Expanded Disability Status Scale), SDMT (Symbol Digit Modalities Test), and MRI.

Results: 182 patients were analyzed (61 remitting-relapsing and 121 progressive-active). 38.5% experienced EBR at least once, but very few (7/182) showed systematic reconstitution. Most patients remained stable upon treatment, regardless of the occurrence of EBR. Dynamics of B cell reconstitution featured increased naïve/transitional B cells, and decreased memory subsets. Homeostasis of the B cell compartment differed at baseline between patients experiencing or not EBR upon treatment. In patients with EBR, reciprocal dynamics of transitional and pro-inflammatory double-negative B cell subsets was associated with better response to rituximab treatment.

Conclusion: EBR is common in rituximab-treated MS patients and is not associated with clinical disease activity. EBR in the peripheral blood may reflect regulatory immunological phenomena in subgroup of patients.

Disclaim These are the views of the author and nobody else

COI None

About the author

MouseDoctor

2 comments

By MouseDoctor

Translate

Categories

Recent Posts

Recent Comments

Archives