Altered immune reconstitution of B and T cells precedes the onset of clinical symptoms of chronic graft-versus-host disease and is influenced by the type of onset

Ann Hematol. 2017 Feb;96(2):299-310. doi: 10.1007/s00277-016-2881-x. Epub 2016 Dec 9.

Abstract

We analyzed lymphocyte subpopulations and cytokines 3 months after allogeneic hematopoietic stem cell transplantation aiming to identify predictive cellular and serum markers for chronic graft-versus-host disease (cGVHD). Samples of 49 patients (pts) (no cGVHD (n = 14), subsequent quiescent onset (n = 16), de novo onset of cGVHD (n = 19)) were analyzed in the absence of active GVHD by flow cytometry and enzyme-linked immunosorbent assay. All mean absolute cell counts are presented as cells per microliter; relative cell counts are presented as percentage of lymphocytes. Pts with subsequent de novo cGVHD had significantly higher relative and absolute counts of CD4+ T cells including higher absolute counts of CD4+ memory T cells (22.36%; 206.55/μl; 136/μl, respectively) compared to pts with subsequent quiescent onset of cGVHD (12.41%; 83.42/μl; 54.3/μl) and pts without cGVHD (10.55%) with regard to relative counts of CD4+ T cells. Similarly, significantly more relative and absolute regulatory T cell numbers (CD4+FOXP3+) were detected in pts with de novo onset of cGVHD (3.08% and 24.63/μl) compared to those in pts without (1.25% and 9.06/μl) or with quiescent onset of cGVHD (1.15% and 6.91/μl). Finally, relative B cell counts, including naïve and memory B cells, were also significantly decreased in pts developing quiescent cGVHD (0.85, 0.73, 0.12% resp.) when compared to pts with de novo onset (5.61, 5.24, 0.38%). The results demonstrate that alterations in immune reconstitution are already present before onset of clinical symptoms and differ between de novo and quiescent onset of disease.

Keywords: Allogeneic hematopoietic stem cell transplantation; BAFF; Bone marrow transplantation; Graft-versus-host disease; Immature B cells.

MeSH terms

  • Adolescent
  • Adult
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytokines / blood
  • Cytokines / immunology
  • Female
  • Graft vs Host Disease / blood
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / immunology*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / trends*
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Time Factors
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / trends
  • Young Adult

Substances

  • Cytokines