The level of IFN-γ in ITP group remained higher after anti-PD-1 blockage, but the levels of IL-4, TGF-β, and IL-17 were not significantly influenced.sPD-1 may cause the dysfunction of PD-1/PD-L1 signaling pathway, and its level is related to the severity of ITP patients.
Compared with vehicle (phosphate-buffered saline), thalidomide significantly inhibited the secretion of IFN-γ and IL-17 in ITP mouse and reduced the expression of CD68 in spleen.
In vitro assays revealed that PD-L1-Fc increased T cell apoptosis, inhibited activation and proliferation of CD4<sup>+</sup> T cells and CD8<sup>+</sup> T cells and decreased IFN-γ and IL-2 secretion in patients with active ITP.
Integrated network pharmacology and metabolomics analysis of the therapeutic effects of ZDF on ITP may be as follows: ZDF counteracts ITP symptoms mainly by inhibiting Ras/MAPKs (Ras/Mitogen-activated protein kinases) pathway, and the expression of upstream protein (Ras) and downstream protein (p-ERK, p-JNK, p-p38) were inhibited, which affects the content of effect index associated with proliferation (Thrombopoietin, TPO; Granulocyte-macrophage colony stimulating factor, GM-CSF), inflammation (Tumor necrosis factor-α, TNF-α; Interleukin-6, IL-6), immune (Interleukin-2, IL-2; Interferon-gamma, IFN-γ; Interleukin-4, IL-4), so that the body's arginine, Δ<sup>12</sup>-prostaglandin j2 (Δ<sup>12</sup>-PGJ2), 9-<i>cis</i>-Retinoic Acid, sphingosine-1-phosphate (S1P), oleic acid amide and other 12 endogenous metabolites significantly changes.
cITP patients had a higher frequency of the IL-4Rα 576 non-QQ genotype compared to healthy subjects (P = 0.04). cITP patients with the IFN-γ +874 non-AA genotype (high expression type) showed more severe thrombocytopenia than those with the AA genotype (P < 0.05). cITP patients had a significantly higher Th1/Th2 ratio than control patients (P < 0.01); this ratio was inversely correlated with platelet counts.
The messenger RNA expression levels of the indicated genes, including HLA-DRB5, IGHV3-66, IFI27, FAM212A, PLD5, tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1β, and IL-4, were significantly increased in patients with ITP compared with healthy humans, while MMP8, SLC1A3, CRISP3, THBS1, FMN1, and IL-10 were decreased.
This meta-analysis indicates that the IFN-γ+874 T/A polymorphism may play a significant role in modifying the risk of autoimmune diseases in Caucasian, Latin American, and Middle Eastern subjects, and in particular shows that the IFN-γ+874 T/A polymorphism is associated with increased genetic susceptibility to idiopathic thrombocytopenic purpura and SLE.
To explore whether TMEVPG1 is involved in ITP, this study examined the TMEVPG1 expression and analyzed the association between TMEVPG1 transcript and IFNG expression in patients with ITP and healthy controls.
APRIL, interleukin-4, and IFN-γ in newly diagnosed ITP group and BAFF, APRIL, interleukin-4, and IFN-γ in chronic ITP group were similar before and after treatment.
The findings in our study suggest that STAT1 rs1467199 SNP plays a potential role in the IFN-γ dependent development of autoimmunity in children with ITP.
We also counted platelets and evaluated plasma IFN-γ, IL-18 and IL-4 levels in patients with active ITP (n=26), patients with ITP in remission (n=23) and in healthy subjects (n=34) by enzyme linked immunosorbent assay (ELISA).
The IFN-γ/IL-4 mRNA (Th1/Th2) expression in ITP patients with active disease and in remission was significantly higher than that in controls (p = 0.0023, p = 0.0125, respectively).
The results showed that IL18 and IFNG protein and mRNA levels were significantly increased in patients with active ITP than in control subjects, but that IL18BP were not significantly elevated in ITP patients, which resulted in an elevated ratio of IL18/IL18BP in patients with active disease.
Of the remaining 6 patients, 4 presented with a Th1 or Th0/Th1 pattern plus IL-10 that persisted after IVIg treatment (although interferon gamma [IFN-gamma] expression diminished) and stabilized to Th1 plus IL-10 at follow-up, which was marked by infrequent episodes of ITP.