No abstract

The data on polarization of the immune system towards T helper 1 (Th1) or T helper 2 (Th2) cells in immune thrombocytopenic purpura (ITP) are limited and contradictory. Th17 characterized by the production of Interleukin 17 (IL-17) has been shown to play a crucial part in the induction of autoimmune diseases. To further investigate the role of Th cytokines in the pathogenesis of ITP, we measured the plasma concentration of three Th17-associated cytokines [IL-17, transforming growth factor-ss (TGF-ss), IL-6] and Th1 cytokine interferon-gamma (IFN-gamma) in ITP patients, and evaluated their clinical relevance. The concentration of IL-17, TGF-ss, IL-6, and IFN-gamma in plasma specimens from 29 adults with chronic ITP and 38 controls was analyzed by enzyme-linked immunosorbent assay method. No significant differences of Th17 cytokines (IL-17, TGF-ss, and IL-6) and Th1 cytokine (IFN-gamma) concentration were observed between patients with active ITP and the control group. And the IFN-gamma/IL-17 ratio representing Th1/Th17 cytokine profile was not significantly different between ITP patients and control, either. However, significantly positive correlation between IL-6 and IFN-gamma in ITP patients was observed (r = 0.48, P = 0.01). Among the ITP patients, Plasma IL-17 levels in male were marginally higher than those in female, while similar for TGF-ss, IL-6 or IFN-gamma. There was a significantly positive correlation between age and IL-6 concentration in ITP patients (r = 0.56, P = 0.0002), while no statistical significance between age and the other three cytokines. No significant correlation between cytokine concentrations and platelets or megakaryocytes number was found in ITP patients. In summary, ITP may not be associated with changes of plasma Th17 and Th1 cytokine concentrations relative to control population.

The human Fcγ receptor (FcγR) system is composed of 2 opposing families, the activating FcγRs (FcγRI, FcγRIIa, and FcγRIII) and the inhibitory FcγR (FcγRIIb). The disturbed balance of the activating and inhibitory FcγRs has been implicated in the pathogenesis of many autoimmune diseases. In this study, the expression of FcγRs on monocytes was determined in 23 patients with primary immune thrombocytopenia (ITP) before and after high-dose dexamethasone (HD-DXM) treatment. The FcγRI expression was significantly higher in ITP patients and decreased after HD-DXM treatment. The ratio of FcγRIIa/IIb mRNA expression on monocytes was significantly higher in untreated patients than in healthy controls. After HD-DXM therapy, the ratio decreased and the increased expression of FcγRIIb mRNA and protein coincided with a remarkable decrease in the expression of FcγRIIa, FcγRI, and monocyte phagocytic capacity. There was no significant difference in FcγRIII expression on monocytes between patients and controls. In vitro cell-culture experiments showed that DXM could induce FcγRIIa and FcγRIIb expression in monocytes from ITP patients, with FcγRIIb at higher amplitudes. These findings suggested that the disturbed FcγR balance might play a role in the pathogenesis of ITP, and that HD-DXM therapy could shift monocyte FcγR balance toward the inhibitory FcγRIIb in patients with ITP.

These results suggest that BAFF expression is increased in ITP patients with active disease, and DXM is an effective inhibitor of BAFF production. As immunosuppressant, DXM may play its role in ITP treatment partly through regulating BAFF expression.

Atractylodis Rhizoma (AR), a kind of well-known traditional Chinese medicine (TCM), has a long history of being used to treat spleen-deficiency syndrome (SDS). Stir frying with bran is a common method of processing AR, as recorded in the Chinese Pharmacopoeia, and is thought to enhance the therapeutic effect in TCM. Our previous studies have confirmed that bran-fried AR is superior to raw AR in terms of the improvement of gastrointestinal tract function. However, the biological mechanism of action is not yet clear. Here, we report the difference between raw and bran-fried AR in terms of the modulatory effect of intestinal microbiota. We found that the composition of intestinal microbiota of SDS rats changed significantly compared with healthy rats and tended to recover to normal levels after treatment with raw and bran-fried AR. Nine bacteria closely related to SDS were identified at the genus level. Among them, the modulatory effect between the raw and bran-fried AR was different. The improved modulation on Bacteroides, Escherichia-Shigella, Phascolarctobacterium, Incertae-Sedis (Defluviitaleaceae Family) and Incertae-Sedis (Erysipelotrichaceae Family) could be the mechanism by which bran-fried AR enhanced the therapeutic effect. Correlation analysis revealed that the modulation on intestinal microbiota was closely related to the secretion and expression of cytokines and gastrointestinal hormones. These findings can help us to understand the role and significance of bran-fried AR against SDS.

No abstract

These results suggest that the activity of IDO enzyme is insufficient in ITP patients. Increased TTS expressions from CD4(+) and CD8(+) T cells might link to a pathogenic mechanism involved in increasing survival of autoreactive T cells in ITP patients.

To investigate the role of Notch signaling pathway in immune thrombocytopenic purpura (ITP), we measured the expression of 11 Notch pathway molecules in ITP patients and evaluated their clinical relevance. Real-time reverse transcriptase polymerase chain reaction results showed there was aberrant expression of some Notch molecules in ITP. Notch1 and Notch3 expression elevated, while Notch2 decreased statistically in ITP patients. As for Notch ligands, only DLL1 was found downregulated in ITP. The expression of Notch target gene, Hes1, was also upregulated. In accordance with the mRNA level, Notch1 and Hes1 protein expression was also found elevated by Western blot. Immunocytochemistry showed that Notch1 expressed highly in the cytomembrane, cytoplasm, and part of cellular nucleus for ITP while weak in cytomembrane for controls, and Hes1 of ITP was found expressed higher in cellular nucleus than that of controls. Our findings suggest that the aberrant expression profile of Notch pathway may be involved in ITP, and blockage of Notch1 pathway is likely a promising therapeutic concept.