Pubertal maturation and T cells in renal transplant recipients

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A.M. Terpstra, A.W. Langerak, C.C. Baan, H. de Jong, M.G.H. Betjes, T. van Gelder, A.C.S. Hokken-Koelega, E.A.M. Cornelissen, A.H. Bouts, J.I. Roodnat, K. Cransberg

Chair(s): dr. Marije C. Baas, nefroloog, Radboudumc, Nijmegen & dr. Dries E. Braat, chirurg, LUMC

Thursday 10 march 2016

15:10 - 15:20h at Zaal 1 & 2

Categories: Parallelsessie (klinisch)

Parallel session: Parallelsessie XII - Klinisch

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Introduction:
The risk of graft loss in renal transplant recipients increases during ages 17-24 years compared to adjacent ages, which can not be fully explained by non-adherence to immunosuppressive medication. In the Adolesce-NT study, we hypothesise that pubertal maturation is associated with increased immune­reactivity and related to the increased graft loss in this high-risk group. Research question: do the characteristics and absolute numbers of CD4+ and CD8+ T cells, B and NK cells differ for pubertal status in end-stage renal disease (ESRD) patients awaiting renal transplantation (RT), RT recipients and healthy controls?

Methods:
We included 42 patients with ESRD (57% male), 54 patients >1 year after RT (67% male) and 53 healthy controls (40% male) aged 10-30 years in our prospective, ongoing study. Puberty was based on age: 10–16 years for healthy females and 11–17 years for healthy males. Given that pubertal maturation is delayed for an average of 1.7 years at RT, puberty in ESRD patients and RT recipients was defined as: ages 12–18 years for females and 13–19 years for males. Three subgroups of pubertal status were defined: before, during and after puberty. Flow cytometric analysis was performed on peripheral blood using a Trucount tube for absolute T, B and NK cell counts and two 8-color labelling to define CD4+/CD8+ T cell subsets: naive, central memory (CM), effector memory CD45RO+ T cells (Temro) and CD45RA+ T cells (Temra). In each study group, differences in lymphocyte counts were compared among pubertal status sub­groups using analysis of variance (ANOVA) models and the Mann–Whitney U test (α level, 0.05).

Results:
In ESRD, the number of CD4+ Temro was higher after puberty (median, 336; IQR, 235–378) than during puberty (206; 177–300; P=0.02) and before puberty (142; 84–213 cells/µL; P=0.002). Also in healthy controls, the number of CD4+ Temro was higher after puberty (median, 355; IQR, 275–465) than during puberty (243; 182–270 cells/µL; P<0.001). In RT recipients, the CD8+ CM T cell count was higher during puberty (median, 3.8; IQR, 1.8–14.5) than after puberty (1.4; 0.6–2.5 cells/µL; P=0.03). Cell counts among other subgroups of pubertal status within the study groups did not significantly differ.

Conclusion:
As memory T cells are key players in allograft rejection, the higher number of CD8+ peripheral CM T cells during puberty in RT recipients may play a role in the higher rate of graft loss in relation to pubertal maturation.