Thymic stromal lymphopoietin levels after allogeneic hematopoietic stem cell transplantation

Abstract

Background

Thymic stromal lymphopoietin (TSLP) is an immunoregulatory, Th2-polarizing cytokine produced by epithelial cells. We hypothesized that TSLP affects immune reconstitution after hematopoietic stem cell transplantation (HSCT) leading to increased alloreactivity.

Methods

We measured plasma TSLP by ELISA in 38 patients and assessed the immune reconstitution by flow cytometry.

Results

TSLP levels rose after initiation of the conditioning to peak at day +21 after HSCT (p = .03), where TSLP levels correlated with counts of neutrophils (rho = 0.36, p = .04), monocytes (rho = 0.58, p = .006), and lymphocytes (rho = 0.59, p = .02). Overall absolute TSLP levels were not associated with acute or chronic graft-vs-host disease (a/cGvHD). However, patients mounting a sustained increase in TSLP levels at day +90 had a higher risk of cGvHD compared to patients who had returned to pre-conditioning levels at that stage (cumulative incidence: 77% vs. 38%, p = .01).

Conclusion

In conclusion, this study suggests a role of TSLP in immune reconstitution and alloreactivity post-HSCT. lymphopoietin (TSLP) is an immunoregulatory, Th2-polarizing cytokine produced by epithelial cells. We hypothesized that TSLP affects immune reconstitution after hematopoietic stem cell transplantation (HSCT) leading to increased alloreactivity. We measured plasma TSLP by ELISA in 38 patients and assessed the immune reconstitution by flow cytometry.

Keywords:

• Thymic stromal lymphopoietin
• hematopoietic stem cell transplantation
• immune reconstitution
• chronic GvHD
• alloreactivity

Author contributions

KK, AEP, LPR, and KM conceived and designed the study. DLM, KK, HS and KM collected the patient samples and clinical data. DLM, KK and CH performed the ELISA analyses. DLM and KK analyzed the data. DLM, KK, and KM drafted the manuscript. All authors revised the manuscript and approved the final version.

Disclosure statement

DLM: Received a grant from the Research Council at Rigshospitalet; KK: Received a grant from Åse og Ejner Danielsens Fond. CHN, HS, AEP, LPR, and KM reported no conflict of interest.

Additional information

Funding

This work was supported by the Research Council at Rigshospitalet and Åse og Ejnar Danielsens Fond. The funding source was not involved in any part of the study design, data collection, data analysis, and interpretation of the data or the writing of this manuscript.