Abnormalities of the Bone Marrow Immune Microenvironment in Patients with Prolonged Isolated Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation

Biol Blood Marrow Transplant. 2017 Jun;23(6):906-912. doi: 10.1016/j.bbmt.2017.02.021. Epub 2017 Mar 9.

Abstract

Prolonged isolated thrombocytopenia (PT) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Whether abnormalities of the bone marrow (BM) immune microenvironment are involved in the pathogenesis of PT remains unknown, however. Twenty patients with PT, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD) were enrolled in this nested case-control study. Th1, Th2, Tc1, Tc2, Th17, and Treg cells were analyzed by flow cytometry, and IFN-γ, IL-4, IL-17, IL-6, IL-21, and thrombopoietin levels in BM plasma were evaluated with a cytometric bead assay and ELISA. Relative to GGF patients and HD controls, PT patients had significantly higher proportions of Th1 and Tc1 cells, resulting in higher Th1/Th2 and Tc1/Tc2 ratios in the BM microenvironment. In addition, the excessive polarization of Th17 was observed in patients with PT. Changes in BM plasma cytokines were consistent with our cellular findings. These results suggest that dysregulated T cell responses in the BM microenvironment might play an important role in the pathogenesis of PT.

Keywords: Allogeneic hematopoietic stem cell transplantation; Bone marrow immune microenvironment; Prolonged isolated thrombocytopenia.

MeSH terms

  • Adolescent
  • Adult
  • Bone Marrow / abnormalities
  • Bone Marrow / pathology*
  • Case-Control Studies
  • Cellular Microenvironment / immunology*
  • Cytokines / blood
  • Female
  • Graft Survival
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Cytotoxic
  • T-Lymphocytes, Regulatory
  • Th1 Cells
  • Th17 Cells
  • Thrombocytopenia / etiology*
  • Thrombocytopenia / pathology
  • Time Factors
  • Transplantation, Homologous
  • Young Adult

Substances

  • Cytokines