![]() However, in the current study, despite the reasonable logic, no benefit was achieved through additional Treg infusions. It is possible that such testing may assist with the selection of patients most likely to respond from HSCT and in identifying patients who may benefit from early interventions, including low-dose maintenance or salvage treatments or additional cellular therapies. Whether more specific assessment of Treg TCR diversity, as described by Delemarre et al, is a better predictor remains to be established. 10 TCR characterization may enable monitoring of pathogenic or protective T-cell clones following autologous HSCT for autoimmune diseases. 9 Outcomes in juvenile idiopathic arthritis have also been related to the degree of thymic processing in reconstituting the T-cell compartment. In MS, restoration of TCR diversity has been reported as a potential predictor of clinical response. Response to autologous HSCT also varies within the same disease and has been related to patient-related factors, such as stage of disease, and there is scope for improving responses and selecting the best patients. 5-10 However, 1 finding common to several diseases, including MS, systemic lupus erythematosus, systemic sclerosis, and juvenile idiopathic arthritis, is enhanced posttransplant levels of Treg cells. ![]() Like clinical responses, the ability to reconstitute varies between diseases and patients. Shifts in T- and B-cell subpopulations from memory to naive cell dominance, with restoration of polyclonal T-cell receptor (TCR) diversity, correction of immune gene expression abnormalities, and other changes in T cells, B cells, plasmablasts, and natural killer cells support immune re-education and tolerization with autologous HSCT. ![]() ![]() Whereas a “debulking of inflammation” is an instantaneous and predictable effect of any high-dose cytotoxic conditioning regimen, sustained clinical responses are best explained by long-term alterations in immune reconstitution via thymic and/or extrathymic pathways. To date, a variety of mechanisms have been proposed to explain the clinical effects (and associated immune “reboot”) of autologous HSCT in severe autoimmune diseases. ![]()
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