The finger is pointing to the B cell with disease reactivation

This is a case report.

Is it a fluke or does it tell us something

Hyun JW, Kim Y, Kim G, Kim SH, Kim HJ Severe B cell-mediated disease activation despite two cycles of alemtuzumab in a patient with multiple sclerosis. Mult Scler. 2018 Nov 7:1352458518810261

Alemtuzumab is a potent monoclonal CD52 antibody used to treat patients with multiple sclerosis (MS). However, recent literature reports have described paradoxical activation of B cell-mediated disease within 1 year of the first cycle of alemtuzumab. We raise awareness that severe B cell-mediated disease activation could develop, even after two cycles of alemtuzumab, in some vulnerable MS patients; therefore, individualized therapeutic strategies should be considered in clinical practice. We also propose that a novel regulatory B-cell subset may be a candidate for a predictive biomarker of disease activation in MS patients treated with alemtuzumab.

What did they find

Time (month)          Memory B x 106/L       Reg          Mature          CD3 T cell
0                    Dose     3.52                           0.95           83.7                 1.88 
6                                 1.86                           10.0           88.6                 0.68
10 Relapse                  2.77                           1.28          281.9                0.64
12                 Dose      1.74                            8.28         125.5                 1.39
15                               1.70                            3.15          28.3                  0.35
21.25                          3.91                           1.38           30.7                  0.40
22 Relapse                 6.66                           1.68           77.9                  0.32

They suggest that deficiency of
CD19+CD24hiCD38hi cells, a novel regulatory
B-cell subset, was observed and may be a candidate
for a predictive biomarker of disease activation in
MS patients treated with alemtuzumab
We know that the stereotyped repopulation is a quick emergence of CD19+, CD38+ CD10+ immature/transitional cells which produce IL-10. A regulatory cell to a T cell immunologist but IL10 is a B cell growth factor needed to repopulate B cells. The regulatory population express CD24+. They give rise to mature.naive B cells.

The person did not deplete that well with about 65% depletion of T cells and memory B cells (48%) at 6 months. Compare this with the long term and persistent depletion of  about 80% depletion in the general population. So by the time they were relapsing the B memory they were 21% down year 1 and double in year 2. So not much of a depletion compared to the 80% depletion with cladribine.

Why won’t Genzyme give me the data?  If this pattern replicates it may tell us something and give use clues of what to look at, but looking at whole T cell numbers has never got us anywhere

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