Altered expression of the TCR signaling related genes CD3 and FcεRIγ in patients with aplastic anemia

Abstract

BackgroundAplastic anemia (AA) is characterized by pancytopenia and bone marrow hypoplasia, which results from immune-mediated hematopoiesis suppression. Understanding the pathophysiology of the immune system, particularly T cells immunity, has led to improved AA treatment over the past decades. However, primary and secondary failure after immunosuppressive therapy is frequent. Thus, knowledge of the immune mechanisms leading to AA is crucial to fundamentally understand the disease.FindingsTo elucidate the T cell receptor (TCR) signal transduction features in AA, the expression levels of CD3γ, δ, ε and ζ chain and FcεRIγ genes, which are involved in TCR signal transduction, and the negative correlation of the expression levels between the CD3ζ and FcεRIγ genes in T cells from peripheral blood mononuclear cells (PBMCs) were analyzed. Real-time RT-PCR using the SYBR Green method was used to detect the expression level of these genes in PBMCs from 18 patients with AA and 14 healthy individuals. The β2microglobulin gene (β2M) was used as an endogenous reference. The expression levels of the CD3γ, CD3δ, CD3ε and CD3ζ genes in patients with AA were significantly increased compared to a healthy control group, whereas the FcεRIγ gene expression level was significantly decreased in patients with AA in comparison with the healthy control group. Moreover, the negative correlation of the expression levels between the CD3ζ and FcεRIγ genes was lost.ConclusionsTo our knowledge, this is the first report of the CD3γ, CD3δ, CD3ε, CD3ζ and FcεRIγ gene expression in patients with AA. The abnormally expressed TCR signaling related genes may relate to T cells dysfunction in AA.

The complex pathophysiology of acquired aplastic anaemia

“…reported that expression levels of the CD3γ, CD3δ, CD3ε and CD3ζ genes were increased significantly in patients with aAA compared to healthy controls. Up‐regulation of CD3 gene expression in aAA suggests that T cells may be in sustained signalling stimulation in the periphery that leads to inappropriate T cell activation . Contradictory to this report, it was found that expression of the CD3 ζ ‐chain was decreased in most patients with aAA .…”

Characteristics of TCRζ, ZAP-70, and FcɛRIγ Gene Expression in Patients with T- and NK/T-Cell Lymphoma

“…The association between a lack of ZAP-70 expression with immunodeficiency consisting of markedly reduced T-cell-mediated immunity highlights the crucial role of this tyrosine kinase in T-cell development and function (Kim et al, 2006;Fischer et al, 2010). The upregulation of FceRIc (Fc epsilon receptor type Ig) expression is observed in peripheral T cells in patients with immunological diseases and T cells that infiltrate tumor sites Li et al, 2012a). Because FceRIc is structurally and functionally homologous to the TCRf chain, it was shown that it could functionally replace deficient TCRf chains, facilitate TCR/CD3 complex-mediated signaling, and participate in the regulation of a variety of immune responses (Krishnan et al, 2003).…”

“…Recently, data have shown that changes in the expression pattern of the TCRf regulating factor, that is, the TCRf 3¢UTR, and the FceRIc and ZAP-70 expression level, as well as their correlation with TCRf might have distinct mechanisms in different immune-related diseases and malignancies (Smedby et al, 2006;Li, 2008;Huang et al, 2012;Li et al, 2012a). In this study, we further analyzed the relative gene expression level of ZAP-70 and FceRIc in a cohort of patients with T-cell NHL (T-NHL) and NK/T-cell lymphoma (NK/T-CL), where TCR signaling regulation is less well understood.…”

Aplastic anemia is related to alterations in T cell receptor signaling

“…In most reports, a significant increase in the CD3γ, CD3δ, CD3ε, and CD3ζ expression levels was detected in peripheral blood samples from newly diagnosed AA patients, which may result in enhancing T cell activation (19,20). Interestingly, the CD3ζ expression level was higher in NSAA compared with SAA patients.…”