Expression of CXCR4 on T-cell subsets and Plasma IL-17 Concentrations in Patients with Aplastic Anaemia

Sci Rep. 2017 Aug 22;7(1):9075. doi: 10.1038/s41598-017-08699-z.

Abstract

Acquired aplastic anaemia (AA) is caused by T-cells migrating to and attacking bone marrow (BM) in response to chemokines (e.g., CXCR4). We investigated CXCR4 expressions on circulating T-cell subsets, plasma IL-17A concentrations, and their correlations with AA manifestations. We enrolled 71 patients with acquired AA (36 severe AA cases [SAA] and 35 non-severe AA cases [NSAA]) and 42 healthy volunteers. We used flow cytometry and ELISA to measure circulating CD4+ and CD8+ T-cells, their CXCR4 expressions, and plasma IL-17A concentrations. Compared to the healthy controls, SAA patients had fewer peripheral CD4+ T-cells, more CD8+ T-cells, and a significantly decreased CD4+/CD8+ ratio which was positively correlated with AA manifestations. Patients with SAA or NSAA had higher proportions of CD4+CXCR4+ and CD8+CXCR4+ T-cells, which were negatively correlated with haemoglobin concentrations and absolute neutrophil counts. Patients with SAA or NSAA had higher plasma IL-17A concentrations, which were negatively correlated with AA manifestations and the CD4+/CD8+ ratio. IL-17A concentrations showed a very week correlation with CD4+CXCR4+ T-cells frequencies, and no correlation with CD8+CXCR4+ T-cells frequencies. Aberrant CXCR4 expression may allow circulating T-cells, especially CD8+ T-cells, to infiltrate BM during AA progression. Elevated IL-17A concentrations may contribute to AA progression outside of the CXCR4-SDF-1α axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anemia, Aplastic / blood*
  • Anemia, Aplastic / diagnosis
  • Anemia, Aplastic / genetics*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • Female
  • Gene Expression*
  • Humans
  • Interleukin-17 / blood*
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Receptors, CXCR4 / genetics*
  • Receptors, CXCR4 / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • Young Adult

Substances

  • CXCR4 protein, human
  • IL17A protein, human
  • Interleukin-17
  • Receptors, CXCR4