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Clin Immunol. 2016 Jun 16;169:47-57. doi: 10.1016/j.clim.2016.06.005. [Epub ahead of print]
Immunological correlates of favorable long-term clinical outcome in multiple sclerosis patients after autologous hematopoietic stem cell transplantation.
Arruda LC1, de Azevedo JT1, de Oliveira GL1, Scortegagna GT2, Rodrigues ES3, Palma PV3, Brum DG4, Guerreiro CT5, Marques VD5, Barreira AA5, Covas DT6, Simões BP6, Voltarelli JC6, Oliveira MC7, Malmegrim KC8.
Abstract
High dose immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) induces prolonged clinical remission in multiple sclerosis (MS) patients. However, how patient immune profiles are associated with clinical outcomes has not yet been completely elucidated. In this study, 37 MS patients were assessed for neurological outcomes, thymic function and long-term immune reconstitution after AHSCT. Patients were followed for a mean (SD) of 68.5 (13.9) months post-transplantation and were retrospectively clustered into progression- and non-progression groups, based on Expanded Disease Status Scale (EDSS) outcomes at last visit. After AHSCT, both patient groups presented increased regulatory T-cell subset counts, early expansion of central- and effector-memory CD8+T-cells and late thymic reactivation. However, the non-progression group presented early expansion of PD-1+CD8+T-cells and of PD-1-expressing CD19+ B-cells. Here, we suggest that along with increased numbers of regulatory T-cell subsets, PD-1 inhibitory signaling is one possible immunoregulatory mechanism by which AHSCT restores immune tolerance in MS patients.
Immunological correlates of favorable long-term clinical outcome in multiple sclerosis patients after autologous hematopoietic stem cell transplantation.
Arruda LC1, de Azevedo JT1, de Oliveira GL1, Scortegagna GT2, Rodrigues ES3, Palma PV3, Brum DG4, Guerreiro CT5, Marques VD5, Barreira AA5, Covas DT6, Simões BP6, Voltarelli JC6, Oliveira MC7, Malmegrim KC8.
Abstract
High dose immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) induces prolonged clinical remission in multiple sclerosis (MS) patients. However, how patient immune profiles are associated with clinical outcomes has not yet been completely elucidated. In this study, 37 MS patients were assessed for neurological outcomes, thymic function and long-term immune reconstitution after AHSCT. Patients were followed for a mean (SD) of 68.5 (13.9) months post-transplantation and were retrospectively clustered into progression- and non-progression groups, based on Expanded Disease Status Scale (EDSS) outcomes at last visit. After AHSCT, both patient groups presented increased regulatory T-cell subset counts, early expansion of central- and effector-memory CD8+T-cells and late thymic reactivation. However, the non-progression group presented early expansion of PD-1+CD8+T-cells and of PD-1-expressing CD19+ B-cells. Here, we suggest that along with increased numbers of regulatory T-cell subsets, PD-1 inhibitory signaling is one possible immunoregulatory mechanism by which AHSCT restores immune tolerance in MS patients.