Abstract Details

Alemtuzumab (LEMTRADA^®) selectively depletes T- and B-lymphocytes. After depletion of the former “diseased MS-immune-repertoire”, a new, “healthy immune repertoire” is assumed to form. Although beneficial for many MS patients, side effects have been described, in particular secondary autoimmunity (SA) occurring in about 1/3 of Alemtuzumab treated patients.

We employ longitudinal peripheral immune repertoire analysis of multiple sclerosis (MS) patients pre- and post-Alemtuzumab treatment to understand better the beneficial properties and potential side effects.

PBMC acquired before, during and after Alemtuzumab treatment from twelve patients with MS and at two time points from five untreated controls were FACS sorted. Defined numbers of the resulting CD4+, CD8+ T cell, and naïve and memory B cell populations were processed for high-throughput immune repertoire sequencing.

In SA patients (5/12), persisting top 100 CD8+ T clones expanded after the first treatment cycle and occupied 9.5%-87% of the corresponding post treatment repertoire volumes; in non-SA patients (7/12) persisting CD8+ clones occupied only 0.28% - 26% of the corresponding post treatment repertoire volumes (p<0.01). Likewise in CD4+ T cell populations, in SA patients, persisting top 100 clones expanded and occupied 3.2%-30% of the corresponding post treatment repertoire volumes as compared to 0.5% - 6.64% in non-SA patients (p<0.007). Conversely, post treatment repertoires of non-SA patients were dominated by new clones, occupying 94.9%-99.6% of the CD4+ and 76.9%-99.77% of the CD8+ T cell repertoire volumes. Post treatment repertoires of SA patients contained smaller volumes of new clones: 76.07% - 97.89% of CD4+ and 13.96% - 91.86% of CD8+ T cell repertoires (p<0.04).

Immune repertoire changes following Alemtuzumab treatment differ significantly between SA-patients and non-SA patients. Further analysis is ongoing to corroborate whether repertoire patterns at baseline may be suited to identify and exclude patients prone to develop secondary autoimmunity from Alemtuzumab treatment.