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Open Access Research article

Reduced plasma levels of soluble interleukin-7 receptor during graft-versus-host disease (GVHD) in children and adults

Thomas Poiret1, Lalit Rane2, Mats Remberger13, Birgitta Omazic13, Åsa Gustafsson-Jernberg4, Nalini Kumar Vudattu5, Raija Ahmed6, Ingemar Ernberg2, Jacek Winiarski4, Isabelle Magalhaes1, Olle Ringden13 and Markus Maeurer137*

Author Affiliations

1 Division of Therapeutic Immunology, Labmed, Karolinska Institutet, Stockholm, Sweden

2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

3 Center for allogeneic stem cell transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden

4 Department of Pediatrics, Astrid Lindgen Barnsjukhuset, Karolinska Hospital Stockholm, Stockholm, Sweden

5 Department of Immunobiology and Internal Medicine, Yale University, New Haven, USA

6 The Public Health Agency of Sweden, Sweden

7 Therapeutic Immunology, F79, LabMed, Hälsovägen, Karolinska University Hospital Huddinge, SE-14186 Huddinge, Sweden

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BMC Immunology 2014, 15:25  doi:10.1186/1471-2172-15-25

Published: 19 June 2014

Abstract

Background

Interleukin 7 (IL-7) signals via the IL-7 receptor (IL-7R) and drives homeostatic T-cell proliferation in patients after allogeneic hematopoietic stem cell transplantation (aHSCT).

Purpose

We performed a prospective study in adults (n = 33) and children (n = 29) undergoing aHSCT measuring plasma IL-7 and soluble IL-7R (sIL-7R) concentrations between 1 and 12 months after HSCT in order to investigate the link between sIL-7R and clinical events after aHSCT.

Results

sIL-7R, but not IL-7, increased with time after HSCT in plasma from all patients enrolled in the study. sIL-7R values were higher at 2, 3, and 6 months (p < 0.01) if the donor was a sibling as compared to an unrelated donor. Increased sIL-7R levels were also identified in plasma from patients who were not treated with anti-thymocyte globulin (ATG). Low sIL-7R was associated with any grade of acute graft-versus-host disease (GVHD) at 2 and 6 months (p = 0.02) and with a positive CMV PCR at 2 months after HSCT (p < 0.05). Patients with cytomegalovirus (CMV) reactivation had increased IL-7 values at 2 and 3 months (p = 0.02) after HSCT. In multivariate analysis, lower sIL-7R levels were associated with acute GVHD (relative hazard (RH): 0.70, p > 0.01) and sibling donors (RH: 2.23, p = 0.004). Recipients of sibling grafts showed high levels of IL-7 (RH: 1.38, p < 0.05) and bone marrow recipients had low IL-7 levels (RH: 0.73, p = 0.04).

Conclusions

Measurement of the sIL-7R/IL-7 axis will help in guided immune monitoring after HSCT and guided interference with sIL-7R may be explored in GVHD management.

Keywords:
HSCT; Interleukin-7; Interleukin-7 receptor; Immune reconstitution; CMV; GVHD