A mathematical model for dynamics of soluble form of DNAM-1 as a biomarker for graft-versus-host disease

PLoS One. 2020 Feb 10;15(2):e0228508. doi: 10.1371/journal.pone.0228508. eCollection 2020.


DNAM-1 (CD226) is an activating immunoreceptor expressed on T cells and NK cells and involved in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We previously reported that a soluble form of DNAM-1 (sDNAM-1) is generated by shedding from activated T cells. Moreover, higher serum levels of sDNAM-1 in patients before allo-HSCT is a predictive biomarker for the development of aGVHD based on the retrospective univariate and multivariate analyses in allo-HSCT patients. However, it remains unclear how the serum levels of sDNAM-1 are regulated after allo-HSCT and whether they are associated with the development of aGVHD. Here, we constructed a mathematical model to assess the dynamics of sDNAM-1 after allo-HSCT by assuming that there are three types of sDNAM-1 (the first and the second were from alloreactive and non-alloreactive donor lymphocytes, respectively, and the third from recipient lymphocytes). Our mathematical model fitted well to the data set of sDNAM-1 in patients (n = 67) who had undergone allo-HSCT and suggest that the high proportion of the first type of sDNAM-1 to the total of the first and second types is associated with high risk of the development of severe aGVHD. Thus, sDNAM-1 after allo-HSCT can be a biomarker for the development of aGVHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Antigens, Differentiation, T-Lymphocyte / blood*
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Biomarkers / analysis
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Female
  • Graft vs Host Disease / blood
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / etiology*
  • Half-Life
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Killer Cells, Natural / metabolism
  • Male
  • Middle Aged
  • Models, Theoretical*
  • Prognosis
  • Retrospective Studies
  • T-Lymphocytes / metabolism
  • Transplantation, Homologous / adverse effects


  • Antigens, Differentiation, T-Lymphocyte
  • Biomarkers
  • CD226 antigen

Grant support

This work was supported in part by grants provided by the Ministry of Education, Culture, Sports, Science and Technology, Japan and the Program for Promotion of Fundamental Studies in Health Science of the National Institute of Biomedical Innovation, Japan.