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CD72 is a co-receptor of B cells and regulates B cell activation. Although aberrant expression of CD72 has been reported in primary immune thrombocytopenia ( ITP), it is uncertain whether this aberrant expression is restricted to specific B cell subsets. Furthermore, the mechanisms that regulate CD72 expression are unknown. In this study, we found higher frequency of CD19+ B cells, CD19+CD27+ memory B cells and lower frequency of CD19+CD27− naive B cells in active ITP patients compared with controls and patients in remission. CD72 expression on CD19+CD27+ cells was upregulated in active ITP patients and correlated with platelet count and anti-platelet autoantibodies. In vitro, CD40L could specifically induce CD72 upregulation on CD19+CD27+ B cells. In combination with CD40L, interleukin ( IL) 10 and BAFF (also termed TNFSF13B) further enhanced CD72 expression on CD19+CD27+ B cells, whereas IL21 reduced CD72 upregulation. CD72 mRNA expression after CD40L stimulation was increased in ITP patients and controls. Significant increase of CD40L on CD4+ T cells was correlated with CD72 expression on CD19+CD27+ B cells in ITP patients. In conclusion, upregulation of CD72 expression on CD27+memory B cells might take part in the pathogenesis of ITP. Elevated CD40L on CD4+ cells combined with cytokines might contribute to the upregulation of CD72 expression on CD27+memory B cells. [ABSTRACT FROM AUTHOR]

Stromal cell-derived factor-1 (SDF-1), signaling through CXCR4, is implicated in megakaryopoiesis and platelet production. SDF-1 rs2297630 is a functional polymorphism in linkage disequilibrium with other functional variants in SDF-1. This study aimed to investigate the role of SDF-1 rs2297630 in chronic ITP. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing. Immature platelet fraction (IPF) was performed using Sysmex XE-2100. Anti-platelet autoantibodies were assayed by enzyme-linked immunosorbent assay. The main characteristics at diagnosis and the outcome of chronic ITP in 201 Chinese patients were retrospectively reviewed. There was no significant difference in either genotype or allelic distribution between ITP patients and the controls (p= 0.114;p= 0.787). However, both heterozygote (GA) and homozygote minor allele (AA) patients had significantly increased megakaryocyte quantity compared to homozygote genotype (GG) patients at diagnosis (p =0.011). The mean IPF values of GA and AA genotype patients were higher than those observed in the GG genotype patients when platelet counts ≤50 × 109/L at diagnosis (p= 0.007). Patients with GA and AA genotype showed a higher response rate to standard treatments than patients with GG genotype (p< 0.001). In particular, GA and AA genotype patients had a significantly increased chance of responding to steroids, intravenous immunoglobulin (IVIG), and thrombopoietin analogs (p= 0.007;p= 0.029;p= 0.034, respectively). No significant difference was found between anti-platelet antibodies and genotypes (p= 0.296). In summary, the SDF-1 rs2297630 was associated with platelet production and treatment response in Chinese patients with chronic ITP. [ABSTRACT FROM AUTHOR]

Background Primary immune thrombocytopenia (ITP) is an immune-mediated disorder in which cellular immunity deficiency and disturbed cytokine profiles have been found. Semaphorin 5A (Sema5A) has been showed to be implicated in cellular immune response. We aimed to evaluate the role of Sema5A in patients with chronic ITP. Methods Plasma levels of Sema5A, T helper (Th) cytokines (interferon [IFN] -γ,interleukin [IL]-4,IL-17A) were determined by enzyme-linked immunosorbent assay (ELISA) in ITP patients and healthy controls. Using real-time quantitative polymerase chain reaction (RT-PCR), mRNA levels of Sema5A and its receptor plexin-B3, plexin-A1 in peripheral blood mononuclear cells(PBMCs)were studied in all subjects. Specific anti-platelet autoantibodies were measured by the Pak Auto method. The dynamic change of plasma Sema5A and mRNA levels of its receptors was measured in 9 patients after effective therapy. Results Plasma Sema5A levels were significantly increased in active patients with chronic ITP compared to patients in remission and healthy controls. Elevated levels of Sema5A were found positively correlated with higher levels of plasma IFN-γ, IFN-γ/IL-4 ratio and negatively correlated with lower levels of plasma IL-4, platelet counts in ITP patients. The mRNA plexin-B3 was decreased in active ITP patients and inversely correlated with plasma Sema5A levels. Additionally, plasma levels of Sema5A and IFN-γ were reduced with up-regulation of plexin-B3 expression after effective treatment. Conclusions Our data demonstrated elevated plasma Sema5A in chronic ITP patients might be involved in Th1 polarization by down-regulating receptor plexin-B3 expression and correlated with disease activity. [ABSTRACT FROM AUTHOR]