Increased bone marrow (BM) plasma level of soluble CD30 and correlations with BM plasma level of interferon (IFN)-γ, CD4/CD8 T-cell ratio and disease severity in aplastic anemia.

Qingqing Wu,Jianfeng Yao,Jun Shi,Xingxin Li,Yizhou Zheng,Meili Ge,Yingqi Shao,Jizhou Zhang,Vassiliki A Boussiotis

doi:10.1371/journal.pone.0110787

Abstract

Idiopathic aplastic anemia (AA) is an immune-mediated bone marrow failure syndrome. Immune abnormalities such as decreased lymphocyte counts, inverted CD4/CD8 T-cell ratio and increased IFN-γ-producing T cells have been found in AA. CD30, a surface protein belonging to the tumor necrosis factor receptor family and releasing from cell surface as a soluble form (sCD30) after activation, marks a subset of activated T cells secreting IFN-γ when exposed to allogeneic antigens. Our study found elevated BM plasma levels of sCD30 in patients with SAA, which were closely correlated with disease severity, including absolute lymphocyte count (ALC) and absolute netrophil count (ANC). We also noted that sCD30 levels were positively correlated with plasma IFN-γ levels and CD4/CD8 T-cell ratio in patients with SAA. In order to explain these phenomena, we stimulated T cells with alloantigen in vitro and found that CD30+ T cells were the major source of IFN-γ, and induced CD30+ T cells from patients with SAA produced significantly more IFN-γ than that from healthy individuals. In addition, increased proportion of CD8+ T cells in AA showed enhanced allogeneic response by the fact that they expressed more CD30 during allogeneic stimulation. sCD30 levels decreased in patients responded to immunosuppressive therapy. In conclusion, elevated BM plasma levels of sCD30 reflected the enhanced CD30+ T cell-mediated immune response in SAA. CD30 as a molecular marker that transiently expresses on IFN-γ-producing T cells, may participate in mediating bone marrow failure in AA, which also can facilitate our understanding of AA pathogenesis to identify new therapeutic targets.

Highlights

Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure syndrome characterized by persistent peripheral blood (PB) pancytopenia and BM hypoplasia [1]
Our findings suggested that CD30 as a cell surface marker that transiently expressed on activated T cells, might be associated with T cell-mediated bone marrow failure in AA, which could facilitate our understanding of AA pathogenesis to identify new therapeutic targets
CD30 was identified as a marker of IFN-c-producing T cells, so we further determined BM plasma IFN-c levels in patients with SAA, and found a positive correlation between soluble CD30 (sCD30) levels and IFN-c levels (Figure 3), which indicated enhanced CD30 signaling might lead to increased production of IFN-c in patients with SAA

Summary

Introduction

Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure syndrome characterized by persistent peripheral blood (PB) pancytopenia and BM hypoplasia [1] Immune abnormalities such as decreased lymphocyte counts, inverted CD4/CD8 T-cell ratio and increased IFN-c-producing T cells have been found in AA [2,3,4]. Recent evidence indicates that oligoclonal expanded cytoxic T cells which are suggestive of an antigen-driven clonal response exist in AA [5,7]. These oligoclones recognize and induce apoptosis of autologous myeloid cells [8]. Other direct evidence to prove the existence of autoantigen in AA is still limited

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