54,55 Our results also showed increased sHLA-G expression in patients responding to HD-DXM (Determine 1D). alleviated thrombocytopenia in a murine model of ITP. In conclusion, our data exhibited that impaired expression of HLA-G and immunoglobulin-like transcripts is usually involved in the pathogenesis of ITP; recombinant HLA-G can correct this abnormality via upregulation of Clodronate disodium immunoglobulin-like transcripts, indicating that HLA-G can be a diagnostic marker and a therapeutic option for ITP. Introduction Immune thrombocytopenia (ITP) is usually a common autoimmune bleeding disorder with decreased platelet counts.1-4 The therapeutic regimens for ITP patients, including glucocorticosteroids, intravenous immunoglobulin, thrombopoietin receptor agonists, rituximab and other immunoregulatory drugs, are not always effective, and only about one-third of ITP patients can achieve longterm remission.5-7 Autoantibodies targeting platelets enhanced T-helper cell activity, initiated abnormal activation of RGS21 cytotoxic T lymphocytes and disturbed cytokine profiles to accelerate platelet clearance and suppress platelet production in ITP patients.1-4,8 Moreover, the deficiency and dysfunction of immunoregulatory cells (i.e., regulatory T cells [Tregs]),9-11 tolerogenic dendritic cells12 and myeloid-derived suppressor cells13 also contribute to the loss of immune tolerance in ITP. HLA-G is usually a nonclassical major histocompatibility complex class I antigen found to be expressed in placental trophoblast cells in 1990s.14 You will find four membrane-bound (mbHLA-G1 to -G4) and three soluble (sHLA-G5 to -G7) isoforms generated by alternative splicing of the primary transcript.15 It was initially believed that HLA-G in placental cells plays an important role in maternal-fetal immunotolerance by interacting with inhibitory receptors (immunoglobulin-like transcript 2 [ILT-2/LILRB1/CD85j], immunoglobulin-like transcript 4 [ILT-4/LILRB2/CD85d] and KIR2DL4 receptor) on leukocytes, which leads to CTL apoptosis, natural killer (NK) cells immobilization, mononuclear cells inhibition and suppressive cytokine environment.16,17 Subsequently HLA-G was found not be restricted to placenta cells, but it is also expressed in human peripheral blood mononuclear cell (PBMC) and plasma.18,19 Additionally to the immune inhibitory capability mentioned above, HLA-G-ILT2/ILT4 interaction suppressed lymphocyte proliferation20,21 and inhibited antibody secretion of activated B cells.21 Suggestions that HLA-G protein facilitates allotransplantation by preventing immune rejection via these actions on immune cells was established. After liver and kidney transplantation, an increased HLA-G level was detected in patients with a reduced incidence of rejection.22-24 Recently, HLA-G-induced immune tolerance has been intensively investigated. The expression of HLA-G (and its cognate Clodronate disodium receptors, ILT) was correlated with immune escape, which suggests unfavorable outcomes in cancer patients.25,26 On the other hand, HLA-G-induced tolerance can benefit patients with autoimmune diseases. Low soluble HLA-G (sHLA-G) level was found in patients with rheumatoid arthritis (RA) and multiple sclerosis, and was associated with disease progression in both cases.27,28 Moreover, the decrease of the number and/or function of ILT2 and ILT4 was involved in the pathogenesis of systemic lupus erythematosus (SLE).29,30 Another study by Kim synthetic HLA-G protein induced the tolerance of skin grafts successfully.33 Nevertheless, little has been defined about the effect of rhHLA-G in autoimmune disease. In this study, we investigated whether there is aberrant HLA/ILT expression and their contribution to the loss of immune tolerance in ITP. Our data showed that this expression of HLA-G and ILT were both decreased in ITP patients, which may result in impaired function of PBMC and dendritic cells (DC). rhHLA-G upregulated ILT on CD4+ T cells and monocytes, and corrected dysfunction of immune cells. These findings show that HLA-G has the potential as a diagnostic marker and therapeutic option for ITP. Methods Patients and controls Plasma samples from Clodronate disodium 50 newly diagnosed ITP patients were collected for the detection of sHLA-G with ELISA. Among them, PBMC from 17 ITP patients were isolated for the investigation of mHLA-G and ILT (Table 1-2). Samples from 15 healthy volunteers were used as controls. The diagnosis of ITP was based on established practice guidelines.1 Fourteen patients with autoantibody received standard ITP treatment high-dose dexamethasone (HD-DXM; 40 mg/day for 4 consecutive days), as explained in the and shown in Table 2. Enrollment took Clodronate disodium place between March 2013 and December 2018. The study was approved by the Medical Ethical Committee of Qilu Hospital, Shandong University or college. Informed consent was obtained from all patients.