"Age Related Differences in the Biology of Chronic Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation"

Abstract

It is established that pediatric hematopoietic stem cell transplant (HSCT) recipients have a lower rate of chronic graft-versus-host disease (cGvHD) compared to adults. Our group has previously published immune profiles changes associated with cGvHD of clinically well-defined adult and pediatric HSCT cohorts. Since all analyses were performed by the same research group and analyzed using identical methodology, we first compared our previous immune profile analyses between adults and children. We then performed additional analyses comparing the T cell populations across age groups, and a sub-analysis of the impact of the estimated pubertal status at time of HSCT in our pediatric cohort. In all analyses, we corrected for clinical covariates including total body irradiation and time of onset of cGvHD. Three consistent findings were seen in both children and adults, including elevations of ST2 and naive helper T (Th) cells and depression of NK_reg cells. However, significant differences exist between children and adults in certain cytokines, B cell, and T_reg populations. In children, we saw a broad suppression of newly formed B (NF-B) cells, whereas adults exhibited an increase in T1-CD21^lo B cells and a decrease in T1-CD24^hiCD38^hi B cells. Prepubertal children had elevations of aminopeptidase N (sCD13) and ICAM-1. T_reg abnormalities in children appeared to be primarily in memory T_reg cells, whereas in adults the abnormalities were in naïve T_reg cells. In adults, the loss of PD1 expression in naïve T_reg and naïve Th cells was associated with cGvHD. We discuss the possible mechanisms for these age-related differences, and how they might theoretically impact on different therapeutic approaches to cGvHD between children and adults.

Keywords: adolescent; adults; children; chronic graft-versus-host disease; immune profile; puberty.