Soluble Interleukin-7 receptor levels and risk of acute graft-versus-disease after allogeneic haematopoietic stem cell transplantation

TY - JOUR

T1 - Soluble Interleukin-7 receptor levels and risk of acute graft-versus-disease after allogeneic haematopoietic stem cell transplantation

AU - Kielsen, Katrine

AU - Shamim, Zaiba

AU - Thiant, Stephanie

AU - Faucher, Sylvie

AU - Decker, Wendy

AU - Christensen, Ib Jarle

AU - Ryder, Lars Peter

AU - Yakoub-Agha, Ibrahim

AU - Müller, Klaus

PY - 2018/2

Y1 - 2018/2

N2 - Interleukin-7 is a cytokine essential for T cell homeostasis. IL-7 binds to cellular IL-7 receptors in competition with a soluble form of the receptor (sIL-7Rα). We hypothesized that altered sIL-7Rα levels may cause adverse outcomes in patients undergoing HSCT. In parallel, we investigated the impact of the IL-7Rα SNP rs6897932, which has been associated with release of IL-7R.The sIL-7Rα levels decreased during HSCT (from 114. ng/ml before to 48. ng/ml at day +. 14 (P <. 0.0001)). This pattern was inversely mirrored by IL-7. The IL-7/sIL-7Rα ratio at day +. 14 was significantly higher in patients developing grade II-IV aGVHD (OR = 4.3, P = 0.026). Furthermore, donor carriage of the rs6897932 T allele was associated with reduced sIL-7Rα levels, increased risk of grades II-IV aGVHD (OR = 2.4, P = 0.055) and increased transplant-related mortality (CC = 4.5%, CT = 21.4% and TT = 27.3%, P = 0.0037). In conclusion, this study suggests an impact of sIL-7Rα levels and rs6897932 donor genotype on alloreactivity and outcome after HSCT.

AB - Interleukin-7 is a cytokine essential for T cell homeostasis. IL-7 binds to cellular IL-7 receptors in competition with a soluble form of the receptor (sIL-7Rα). We hypothesized that altered sIL-7Rα levels may cause adverse outcomes in patients undergoing HSCT. In parallel, we investigated the impact of the IL-7Rα SNP rs6897932, which has been associated with release of IL-7R.The sIL-7Rα levels decreased during HSCT (from 114. ng/ml before to 48. ng/ml at day +. 14 (P <. 0.0001)). This pattern was inversely mirrored by IL-7. The IL-7/sIL-7Rα ratio at day +. 14 was significantly higher in patients developing grade II-IV aGVHD (OR = 4.3, P = 0.026). Furthermore, donor carriage of the rs6897932 T allele was associated with reduced sIL-7Rα levels, increased risk of grades II-IV aGVHD (OR = 2.4, P = 0.055) and increased transplant-related mortality (CC = 4.5%, CT = 21.4% and TT = 27.3%, P = 0.0037). In conclusion, this study suggests an impact of sIL-7Rα levels and rs6897932 donor genotype on alloreactivity and outcome after HSCT.

KW - Acute graft-versus-host disease

KW - Allogeneic HSCT

KW - IL-7Rα SNPs

KW - Soluble IL-7R

U2 - 10.1016/j.clim.2017.08.015

DO - 10.1016/j.clim.2017.08.015

M3 - Journal article

C2 - 28863969

AN - SCOPUS:85032329389

SN - 1521-6616

VL - 187

SP - 26

EP - 32

JO - Clinical Immunology

JF - Clinical Immunology

ER -