Background:

The developing immune system of childhood promotes better graft acceptance and longevity but also higher risk for infections and post-transplant (Tx) lymphoproliferative disorders. This may be due to lack of memory B-cells or higher proportions of immune modulatory B-cells (CD24hCD38h transitional (TrB) and CD5+CD1d high (Breg)). We assessed the role of age, transplant and organ type on B-cell maturation around Tx.

Methods:

115 children listed for Tx (51 kidney, 35 liver, 29 heart) were enrolled in the POSITIVE study, a multicenter collaboration within the Canadian National Transplant Research Program (CNTRP). Samples were collected at listing, 3 and 12 months post-transplant. Isolated Peripheral blood mononuclear cells were analyzed for phenotypes by multicolor flow cytometry. Participants were separated into Infant (0-2 years), child (2-10y) and teenager (10-17y) age groups.

Results:

Pre-Tx infants had higher B-cell proportions than children and teenager (p=0.01), but fewer CD 27+ memory B-cells of IgM+ (p<0.05) and switched IgM- (p<0.01) phenotype. Memory B-cells increased with age throughout childhood (p<0.05). Memory B cell development was not affected by Tx but showed similar age related increase similar to cross sectional values of pre-Tx children despite immune suppression. TrB were higher in infants (p<0.05) and declined to adult values thereafter (p<0.05). Pre-Tx, liver recipients had more B-cells, TrB and CD21+ B-cells (p<0.05) and kidney less CD4+ and more CD8+ T-cells (p<0.05) compared to other organ groups, while post-Tx all organ groups were similar, showing lower CD4+ and higher CD8+ T-cells than pre-Tx. Breg proportion was not associated with age, Tx stage or organ type.

Conclusions:

While Tx and immune suppression significantly alter T-cell proportions in childhood, B-cells show a similar maturation profile with age as in a non-manipulated immune system. Lack of memory and increased proportions of immature B-cells likely contribute to the better graft acceptance in infants. The role of the individual immune profile and organ related differences on the clinical course are being prospectively assessed in long term follow-up.

CITATION INFORMATION: Ionescu L., Blydt-Hansen T., Foster B., Mital S., Hamiwka L., Allan U., Phan V., Birk P., Morgan C., Urschel S. The Impact of Childhood Solid Organ Transplantation on B-Cell Maturation Am J Transplant. 2017;17 (suppl 3).

« Back to 2018 American Transplant Congress