Metabolic Complications Precede Alloreactivity and Are Characterized by Changes in Suppression of Tumorigenicity 2 Signaling

Romany A N Johnpulle, Sophie Paczesny, Dae Kwang Jung, Etienne Daguindau, Madan H. Jagasia, Bipin N. Savani, Wichai Chinratanalab, Robert F. Cornell, Stacey Goodman, John P. Greer, Adetola A. Kassim, Salyka Sengsayadeth, Michael T. Byrne, Brian G. Engelhardt

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

New-onset post-transplantation diabetes mellitus (PTDM) occurs commonly after allogeneic hematopoietic cell transplantation (HCT) and is associated with inferior survival. We hypothesize that PTDM and nonrelapse mortality (NRM) are related to IL-33/suppression of tumorigenicity 2 (ST2) signaling and that soluble ST2 (sST2) levels will predict PTDM diagnosis. sST2 was measured at engraftment and day +30 in 36 euglycemic HCT recipients followed prospectively for PTDM (cohort 1). Results were confirmed in a validation cohort of 26 patients without pre-existing diabetes analyzed retrospectively for PTDM (cohort 2). Twelve patients with established diabetes before HCT were analyzed in cohort 3. When compared with recipients without PTDM, patients developing PTDM (n = 24) from cohort 1 had elevated sST2 levels at engraftment (P = .02) and at day +30 (P < .01). Cohort 2 confirmed this finding at engraftment (P = .01). Cohort 3 patients with pretransplantation diabetes had higher sST2 at engraftment than patients maintaining euglycemia after HCT from cohort 2 (P = .03). Multivariate analysis of cohorts 1 and 2 showed high engraftment sST2 predicted increased PTDM and NRM risk, independent of conditioning and grades 3 to 4 acute graft-versus-host-disease. sST2 was elevated in PTDM, indicating a relationship between glucose homeostasis and the IL-33/ST2 axis after transplantation. Correction of metabolic complications may decrease sST2 and improve NRM.

Original languageEnglish (US)
Pages (from-to)529-532
Number of pages4
JournalBiology of Blood and Marrow Transplantation
Volume23
Issue number3
DOIs
StatePublished - Mar 1 2017

Keywords

  • Allogeneic
  • IL-33
  • Metabolic complications
  • Post-transplantation diabetes mellitus
  • Soluble suppression of tumorigenicity 2
  • sST2
  • Treatment-related mortality

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Johnpulle, R. A. N., Paczesny, S., Jung, D. K., Daguindau, E., Jagasia, M. H., Savani, B. N., Chinratanalab, W., Cornell, R. F., Goodman, S., Greer, J. P., Kassim, A. A., Sengsayadeth, S., Byrne, M. T., & Engelhardt, B. G. (2017). Metabolic Complications Precede Alloreactivity and Are Characterized by Changes in Suppression of Tumorigenicity 2 Signaling. Biology of Blood and Marrow Transplantation, 23(3), 529-532. https://doi.org/10.1016/j.bbmt.2016.12.627