The TCR Repertoire Reconstitution in Multiple Sclerosis: Comparing One-Shot and Continuous Immunosuppressive Therapies

Abstract

has not yet been established hindering insight into the posttreatment TCR landscape of MS patients. To address this important knowledge gap, we tracked peripheral T-cell subpopulations (naive and memory CD4+ and CD8+) across 15 RRMS patients before and after 2 years of continuous treatment (NTZ) and a single treatment course (AHSCT) by high-throughput TCRβ sequencing. We found that the two MS treatments left treatment-specific multidimensional traces in patient TCRβ repertoire dynamics with respect to clonal expansion, clonal diversity, and repertoire architecture. Comparing MS TCR sequences with published datasets suggested that the majority of public TCRs belonged to virus-associated sequences. In summary, applying multidimensional computational immunology to a TCRβ dataset of treated MS patients, we show that qualitative changes of TCRβ repertoires encode treatment-specific information that may be relevant for future clinical trials monitoring and personalized MS follow-up, diagnosis, and treatment regimens.

Early changes in IL‐21, IL‐22, CCL2, and CCL4 serum cytokines after outpatient autologous transplantation for multiple sclerosis: A proof of concept study

“…There are limitations in our proof of concept study, and they include that the time point for ILs determination was too early to detect a sustained effect of AHSCT on the immune system of MS patients and on their disease; also, an assessment of lymphocyte subsets could have been ideally carried out at the time of ILs post‐transplant assessment. In this respect, the post‐transplant T‐cell receptor (TCR) landscape of MS relapse‐remitting MS patients has been recently studied, documenting changes on TCR‐ß repertoire dynamics in relation to clonal expansion, clonal diversity, and repertoire architecture 37 …”

TCR repertoire diversity in Multiple Sclerosis: High-dimensional bioinformatics analysis of sequences from brain, cerebrospinal fluid and peripheral blood

“…ShannonÀEvenness (S-E) is defined as the quotient of the exponential of the Shannon entropy and species richness (SR: number of unique CDR3s in a given TCR database) [25,26].…”

“…A TCR Vb clone (V-J-CDRb3 a.a.) was considered private when present in the repertoires of only one individual and public when shared across repertoires of at least two individuals or shared with T cell Vb clones present in one of the public databases below [25].…”

“…1b), thereby showing sufficient sequencing depth. [25] The number of reads for each analyzed database is reported in Supplementary Fig 1.…”

“…Cluster analysis of clonal expansion across repertoires gives the possibility to link similarity of TCR repertoire polarization by the use of established Hill-based evenness profiles [25,26]. The heatmap in Fig.…”