Basaal I - P37 - End stage renal disease patients have a skewed T cell receptor Vbeta repertoire

L. Huang, A.W. Langerak, I.L.M. Wolvers-Tettero, R.W.J. Meijers, C.C. Baan, N.H.R. Litjens, M.G.H. Betjes

Chair(s): dr. Michiel Betjes, Erasmus MC, Rotterdam

Thursday 10 march 2016

13:00 - 13:30h at Foyer

Categories: Postersessie

Parallel session: Postersessies XI - Opgesplitst in 3 tijdblokken en 3 categoriëen (klinisch, basaal, donatie)

Introduction:
End stage renal disease (ESRD) is associated with a defective T-cell mediated immunity, resembling premature T-cell ageing. A diverse T-cell receptor Vbeta (TCR Vβ) repertoire is central to effective T-cell mediated immune responses to foreign antigens. In this study, the effect of ESRD on TCR Vβ repertoire diversity was assessed and associated with T-cell ageing parameters.

Patients, materials and methods:
Forty-five stable ESRD patients on the waiting list for their first kidney transplantation and 51 healthy individuals (HI) were included, matched for age and cytomegalovirus (CMV) serostatus. Twenty-one patients were within the young group (age 19 – 45 years) and 24 patients belonged to the elderly group (age 65 – 77 years). Patients with any clinical or laboratory evidence of acute bacterial or viral infection, malignancy, immunosuppressive drugs treatment within 28 days prior to transplantation (expect glucocorticoids) were excluded. Blood was drawn prior to transplantation of ESRD patients. The TCR Vβ repertoire was measured by a qualitative DNA-based multiplex TCR Vβ gene PCR. In addition, T cell ageing parameters like thymic output, evaluated by CD31-expressing naive T cells, differentiation status and relative telomere length (RTL) of T cells were assessed by flow cytometry.

Results:
A higher proportion of, in particular, elderly ESRD patients (87.5%) had a skewed TCR Vβ repertoire compared to age- and CMV serostatus-matched HI (32.0%, P<0.001). Age (odds ratio, OR, =2.3, P<0.05 ), CMV-serostatus (OR=6.7, P<0.05) and ESRD (OR=4.8, P<0.05) were independently associated with skewing of the TCR Vβrepertoire. Skewing of the TCR Vβ repertoire significantly occurred in CD8+, but not CD4+, memory T cells subsets in the elderly ESRD patients. More differentiated CD8+ T cells, i.e. highly differentiated effector memory T cells (EMRA) and CD28null T cells, were observed in young ESRD patients with a shifted TCR Vβ repertoire compared with those without a shifted TCR Vβ repertoire. Thymic output and relative telomere length of T cells were not significantly related to TCR Vβ skewing.

Conclusions:
ESRD significantly skewed the TCR Vβ repertoire, which may contribute to the uremia-associated defect in T-cell mediated immunity.