The role of soluble HLA-G and HLA-G receptors in patients with hematological malignancies after allogeneic stem cell transplantation

Med Oncol. 2015 Aug;32(8):219. doi: 10.1007/s12032-015-0664-1. Epub 2015 Jul 18.

Abstract

HLA-G is a non-classical MHC class I molecule whose suppressive activity on immune effector cells is exerted due to interactions with receptors ILT2, ILT4 and KIR2DL4. These receptors are expressed mainly on NK cells and monocytes, and their intensity of expression changes depending on HLA-G level. HLA-G plays an important role in the development of tolerance following organ transplantations and bone marrow stem cell transplantations. HLA-G also participates in the modulation of the immune response during cancerogenesis. The aim of this study was to assess HLA-G level in blood serum, the percentage of NK cells and monocytes with expression of receptors for HLA-G (ILT2, ILT4, KIR2DL4 and NKG2D) in patients who received allogeneic stem cell transplantations, and their influence on the occurrence of graft-versus-host reaction. The study included 32 patients with bone marrow diseases (acute leukemias, myelodysplastic syndrome, chronic myeloid leukemia, paroxysmal nocturnal hemoglobinuria) who received allogeneic stem cell transplantations. We assessed the expression of receptors ILT2, ILT4, KIR2DL4 and NKG2D on monocytes and NK cells, as well as the level of HLA-G in blood serum in patients before conditioning, in the transplant hematopoietic reconstitution period following allogeneic bone marrow stem cell transplantation. The percentage of NK cells with expression of KIR2DL4, ILT2 and ILT4 receptors was higher in patients with 0-I grade GVHD than in patients with II-IV grade GVHD. The percentage of monocytes with expression of ILT4 and ILT2 receptors was higher in patients with 0-I grade GVHD than in patients with II-IV grade GVHD. The level of HLA-G in patients' blood serum was higher after the stem cell transplantation compared with the period before transplantation. HLA-G level and HLA-G receptors are related to intensity of GVHD and may play the role of a prognostic factor for the development of GVHD and the clinical course of this reaction.

Publication types

  • Clinical Study

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD / blood
  • Bone Marrow Transplantation
  • Female
  • Graft vs Host Disease / immunology
  • HLA-G Antigens / blood*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / surgery*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Killer Cells, Natural / immunology
  • Leukocyte Immunoglobulin-like Receptor B1
  • Male
  • Membrane Glycoproteins / blood
  • Middle Aged
  • Monocytes / immunology
  • NK Cell Lectin-Like Receptor Subfamily K / blood
  • Receptors, Immunologic / blood*
  • Receptors, KIR2DL4 / blood
  • Transplantation, Homologous
  • Young Adult

Substances

  • Antigens, CD
  • HLA-G Antigens
  • KIR2DL4 protein, human
  • KLRK1 protein, human
  • LILRB1 protein, human
  • LILRB2 protein, human
  • Leukocyte Immunoglobulin-like Receptor B1
  • Membrane Glycoproteins
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, KIR2DL4