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. 2014 Jun 19:15:25.
doi: 10.1186/1471-2172-15-25.

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

Thomas Poiret, Lalit Rane, Mats Remberger, Birgitta Omazic, Asa Gustafsson-Jernberg, Nalini Kumar Vudattu, Raija Ahmed, Ingemar Ernberg, Jacek Winiarski, Isabelle Magalhaes, Olle Ringden, Markus Maeurer  1
Affiliations

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

Thomas Poiret et al. BMC Immunol. .

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.

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Figures

Figure 1
Figure 1
Immune reconstitution measured as absolute leukocyte counts (left figures) and CD4 and CD8 T-cell frequency after HSCT in blood from adults and children. * = p < 0.05. Note that leukocyte counts were available from children at the time of transplantation (0) and 1–3 months after HSCT.
Figure 2
Figure 2
Percentage of CD127+ (IL-7R+) T-cells in patients after HSCT. Blood was taken at different time points after HSCT and CD127 expression was analyzed by flow cytometry on CD3+, CD3+CD4+, and CD3+CD8+ T-cells in PBMCs from adults and children.
Figure 3
Figure 3
Levels of soluble Il-7R (sCD127, left figures) and IL-7 (right figures) in plasma from adults and children after HSCT. * = p < 0.05. Plasma was obtained at different time points after HSCT and examined for IL-7 and sIL-7R by ELISA. Median levels are marked with a bar. sIL-7R levels increased with time after HSCT (non-parametric Wilcoxon test). Differences in plasma from children: 2 months after aHSCT as compared to 1 month (p = 0.02), 3–4 months vs. 1 month (p = 0.04), 5–7 months vs. 1 month (p = 0.02) and 12–14 months vs. 1 month (p = 0.03).
Figure 4
Figure 4
sIL-7R levels after HSCT and analysis of clinical endpoints, i.e. type of donor (HLA-identical sibling (sib) or unrelated donor [32] and HLA-match versus HLA-mismatch.
Figure 5
Figure 5
Levels of sIL-7R and IL-7 after HSCT, cytomegalovirus (CMV) reactivation (CMV PCR positivity) versus no CMV infection/reactivation, acute graft-versus-host disease (GVHD) grades I–IV versus no GVHD and stage of disease: early versus late.
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