Characterization of the T-cell Repertoire after Autologous HSCT in Patients with Ankylosing Spondylitis

摘要

Autologous hematopoietic stem cell transplantation (HSCT), a safer type of HSCT than allogeneic HSCT, is a promising therapy for patients with severe autoimmune diseases (ADs). Despite the long history of medical practice, structural changes in the adaptive immune system as a result of autologous HSCT in patients with various types of ADs remain poorly understood. In this study, we used high-throughput sequencing to investigate the structural changes in the peripheral blood T-cell repertoire in adult patients with ankylosing spondylitis (AS) during two years after autologous HSCT. The implementation of unique molecular identifiers allowed us to substantially reduce the impact of the biases occurring during the preparation of libraries, to carry out a comparative analysis of the various properties of the T-cell repertoire between different time points, and to track the dynamics of both distinct T-cell clonotypes and T-cell subpopulations. In the first year of the reconstitution, clonal diversity of the T-cell repertoire remained lower than the initial one in both patients. During the second year after HSCT, clonal diversity continued to increase and reached a normal value in one of the patients. The increase inthe diversity was associated with the emergence of a large number oflow-frequency clonotypes, which were not identified before HSCT. Efficiency ofclonotypes detection after HSCT was dependent on their abundance in the initialrepertoire. Almost all of the 100 most abundant clonotypes observed before HSCTwere detected 2 years after transplantation and remained highly abundantirrespective of their CD4+ or CD8+ phenotype. A total of up to 25% ofperipheral blood T cells 2 years after HSCT were represented by clonotypes fromthe initial repertoire.