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X. Li et al.
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Figure 3. rhHLA-G reprogrammed cytokine profile in immune thrombocytopenia patients. Peripheral blood mononuclear cells (PBMC) were cultured with or without recombinant human leukocyte antigen-G (rhHLA-G) for 3 days and supernatants were collected. (A-J) Cytokine levels in the culture supernatant from 17 immune thrombocytopenia (ITP) patients and 15 healthy controls were determined by Bio-plex Multiple Cytokine Test. (K) Percentage of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in CD4+ cells with or without rhHLA-G modulation from 10 randomly selected ITP patients and 8 healthy controls. *P<0.05; **P<0.01.
on the same day; group 3 received 7.5 ug HLA-G protein; group 4 received the same volume of phosphate-buffered saline as a blank control. According to routine monitored platelet counts, mice in group 1 showed significantly high- er platelet counts than mice in group 2 at week 3 and 4 after irradiation. Mice in group 3 showed significantly higher platelet counts than mice in group 4, but lower platelet counts than mice in group 1 (Figure 6C). No signif- icant difference in the survival rate among the four groups was observed in our study (Figure 6B).
Discussion
ITP is characterized by autoantibody-mediated platelet phagocytosis,1-3 in which the number deficiency and/or dysfunction of immune regulatory cells, such as Tregs, tolerogenic DC, and MDSC, leads to the loss of immune
tolerance in ITP patients. As an important immunoregula- tory molecule, HLA-G executes its inhibitory immune function through suppression of T cells, B cells, and APC.16,19
In this study, the levels of sHLA-G in ITP plasma is cor- related with the presence of anti-platelet autoantibodies, but no significant difference was observed between Ab- negative ITP patients and healthy controls, indicating the involvement of HLA-G in the pathogenesis of autoanti- body-mediated platelet clearance. A previous study showed that HLA-G inhibited B-cell proliferation and antibody secretion,21 which may explain why patients with low levels of sHLA-G tended to have high levels of anti-platelet antibodies. Furthermore, sHLA-G positively correlated with platelet counts in ITP patients and in healthy controls, suggesting that HLA-G may have other protective effects.
sHLA-G exerts its inhibitory immune function by inter-
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haematologica | 2021; 106(3)