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.
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.
Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, P.R.CHINA.
Qingqing
Q
Wu
Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, P.R.CHINA.
Jizhou
J
Zhang
Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, P.R.CHINA.
Jun
J
Shi
Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, P.R.CHINA.
Meili
M
Ge
Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, P.R.CHINA.
Xingxin
X
Li
Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, P.R.CHINA.
Yingqi
Y
Shao
Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, P.R.CHINA.
Jianfeng
J
Yao
Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, P.R.CHINA.
Yizhou
Y
Zheng
D000328:Adult; D000741:Anemia, Aplastic / Q000097:blood / Q000473:pathology*; D001853:Bone Marrow / Q000098:blood supply*; D016516:CD4-CD8 Ratio / Q000706:statistics & numerical data*; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D017730:Ki-1 Antigen / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D060888:Real-Time Polymerase Chain Reaction
D017931:DNA Primers; D017730:Ki-1 Antigen; D007371:Interferon-gamma