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

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.

Elevated Serum Levels of Soluble CD30 in Ankylosing Spondylitis Patients and Its Association with Disease Severity-Related Parameters

“…Several studies have demonstrated the potential value of measuring serum sCD30 levels in diagnosing and monitoring serious pathological conditions, including diseases due to malignancy, autoimmunity, and viruses [ 4 , 9 – 14 , 20 ]. However, only one clinical trial to date has assessed serum sCD30 levels in AS patients [ 21 ].…”

CD8 + T cells drive autoimmune hematopoietic stem cell dysfunction and bone marrow failure

“…While CD4 + T cells are clearly established in their central role of inducing autoimmune BM failure, our results here demonstrate that CD8 + T cells promote the ability of CD4 + T cells to enter or expand within the BM, thus severely exacerbating BM disease. CD8 + T cells, which have clinically been known to expand in the BM during BM failure, including aplastic anemia, BM transplant and myelodysplastic syndrome [10, 11, 24-26], are similarly highly expanded in IL-2 −/− BM. While IL-2 −/− CD4 + T cells alone are capable of transferring mild disease, onset of BM dysregulation and development of anemia is much more severe and rapid with the co-transfer of IL-2 −/− CD8 + T cells.…”

Preeclampsia is Characterized by Fetal NK Cell Activation and a Reduction in Regulatory T Cells

“…The CD4/CD8 T-cell ratio is an important marker of many human diseases most prominently human immunodeficiency virus infection, but also idiopathic aplastic anemia, leprosy, sarcoidosis, and others with an inverted ratio correlating to increased inflammation. [27][28][29][30] In normal fetuses, the CD4/CD4 ratio is comparable to adults, while in the cord blood of babies affected by fetal growth restriction, higher CD4/CD8 ratios have been observed. 21,31 In line with this observation, we found increased CD4/CD8 T-cell ratios in the cord blood of fetuses born to preeclamptic mothers indicating increased inflammation.…”