Human leukocyte antigen-G upregulates immunoglobulin-like transcripts and corrects dysfunction of immune cells in immune thrombocytopenia

Abstract

Human leukocyte antigen-G is a non-classical major histocompatibility complex class I antigen with potent immune-inhibitory function. Human leukocyte antigen-G benefit patients in allotransplantation and autoimmune diseases by interacting with its receptors, immunoglobulin-like transcripts. Here we observed significantly less human leukocyte antigen-G in plasma from immune thrombocytopenia patients positive for anti-platelet autoantibodies compared with autoantibodies-negative patients or healthy controls. Besides, human leukocyte antigen-G is positively correlated with platelet counts in both patients and healthy controls. We also found less membrane-bound human leukocyte antigen-G and immunoglobulin-like transcripts on CD4+ and CD14+ cells in patients. Recombinant human leukocyte antigen-G upregulated immunoglobulin-like transcript 2 expression on CD4+ and immunoglobulin-like transcript 4 on CD14+ cells. Human leukocyte antigen-G upregulated IL-4 and IL-10, and downregulated tumor necrosis factor-α, IL-12 and IL-17 secreted by patient peripheral blood mononuclear cells, suggesting a stimulation of Th2 differentiation and downregulation of Th1 and Th17 immune response. Human leukocyte antigen-G-modulated dendritic cells from immune thrombocytopenia patients showed decreased expression of CD80 and CD86, and suppressed CD4+ T-cell proliferation compared to unmodulated cells. Moreover, human leukocyte antigen-G modulated cells from patients induced less platelet apoptosis. Human leukocyte antigen-G administration also significantly alleviated thrombocytopenia in a murine model of ITP. In conclusion, our data demonstrated that impaired expression of human leukocyte antigen-G and immunoglobulin-like transcripts is involved in the pathogenesis of immune thrombocytopenia; Recombinant human leukocyte antigen-G can correct this abnormality via upregulation of immunoglobulin-like transcripts, indicating that human leukocyte antigen-G can be a diagnostic marker and a therapeutic option for immune thrombocytopenia.