Abnormal expression of b10 cell frequencies: possible relation to pathogenesis and disease severity of aplastic anemia

Abstract

SUMMARY OBJECTIVE: Aplastic anemia (AA) is an immune-mediated disease that destroys hematopoietic cells through activated T lymphocytes. B lymphocyte-mediated humoral immunity also plays an important role in the pathogenesis of AA. Regulatory B cell (Breg) subpopulation, which is defined as “B10”, secretes interleukin 10 (IL-10). The objective of our experiment was to investigate whether the scale-down proportion of B10 cells in AA patients may play a key role in the pathogenesis. METHODS: A total of 38 AA patients (14 SAA patients and 24 NSAA patients) and 20 healthy control subjects were included. All subjects did not suffer from autoimmune diseases or any other diseases affecting the immune system, such as infectious diseases. Bone marrow mononuclear cells (PBMCs) were isolated and analyzed by Flow cytometry (FCM) and Immunofluorescence double-labeling assay. The relationship between the relative proportions of B10 and ProB10 and their associations to AA, as well as disease severity, were assessed by common clinical indicators and then examined. RESULTS: Our analyses revealed AA patients had significantly lower proportions of peripheral B10 and B10pro compared to healthy controls. SAA patients had a substantially lower percentage of B10 cells and B10pro cells compared to NSAA patients. In addition, B10 cells and B10pro cells were negatively correlated with absolute neutrophil counts, hemoglobin levels and platelet, and absolute reticulocyte counts in AA patients. CONCLUSIONS: The present study attempted to elucidate the potential role of the scale-down proportion of B10 cells in the pathogenesis of AA.

Deficit of circulating CD19+CD24hiCD38hi regulatory B cells in severe aplastic anaemia

“…IL‐10‐producing B cells in bone marrow have been reported to be reduced in patients with AA compared to healthy individuals; 32 we confirmed this finding in peripheral blood, because marrow samples are diluted by peripheral blood, perhaps more so with hypocellular samples. Further the reduction of IL‐10 + B cells associated with the quantitative deficit of CD24 hi CD38 hi Bregs, but residual CD24 hi CD38 hi Bregs in AA were functional, as they produced IL‐10 in response to CpG and CD40L.…”

“…B cells that produce IL‐10 in response to CpG and CD40L stimulation were also significantly reduced in 33 patients with AA compared to 12 healthy individuals (median [IQR] 1·7 [1·1–2·4]% vs. 3·0 [2·4–4·4]%, P = 0·0017; Fig 3B), as observed by others, 32 and they showed a positive correlation with CD24 hi CD38 hi Bregs ( r = 0·37, P = 0·012). IL‐10 production from CD24 hi CD38 hi Bregs was analysable only in 10 of the 33 patients with AA, in which CD24 hi CD38 hi Bregs were retained but still these were significantly reduced compared to the 12 healthy individuals (median [IQR] 0·76 [0·31–2·2]% vs. 2·8 [2·0–4·1]%, P = 0·0056).…”

“…Peripheral blood CD19 + B‐cell frequencies are higher in AA compared to myelodysplastic syndrome 31 . IL‐10 producing B cells in bone marrow are reduced in AA, suggesting that Breg defects might contribute to the pathophysiology 32 . In the present study, we evaluated peripheral blood B‐cell subpopulations, including CD24 hi CD38 hi Bregs, as well as total B cells, CD4 + T cells, CD8 + T cells and natural killer (NK) cells, at diagnosis and 6 months after institution of IST plus eltrombopag, and further tested their correlations with clinical presentations and outcomes after therapy.…”

Cyclosporine Monotherapy in Pediatric Patients With Non-severe Aplastic Anemia: A Retrospective Analysis

“…Another reason was that 6 of 8 transfusion-dependent patients in our study were platelet transfusion-dependent and further univariate analyses revealed that lower platelet count predicted an active response to CsA. Meanwhile, patients with higher IL-10 level seem to have a better response to CsA, which is easy to be understood since IL-10 are defined as stimulator of hematopoiesis ( 22 ). Higher level of HbF tend to have negative response to CsA monotherapy.…”