Up-regulation of NKG2A Inhibitory Receptor on Circulating NK Cells Contributes to Transfusion-induced Immunodepression in Patients with β-thalassemia Major

Accumulating evidence has shown that allogeneic blood transfusions can induce significant immunosuppression in recipients, and thereby increase the risk of postoperative infection and/or tumor relapse. Although it is well known that natural killer（NK） cells are responsible for the immunodepression effects of transfusion, the underlying mechanisms remain obscure. In this study, we investigated the role of NK cells in transfusion-induced immunodepression in β-thalassemia major. The proportion of circulating NK cells and the expression of NK receptors（NKG2A, CD158 a, NKP30, NKP46 and NKG2D） as well as CD107 a were detected by multicolor flow cytometry. IFN-γ production by circulating NK cells was detected by intracellular cytokine staining. Our results showed that the proportion and cytotoxicity（CD107a expression） of circulating NK cells in transfusion-dependent β-thalassemia major patients were remarkably lower than those of β-thalassemia minor patients or healthy volunteers. Expression of NKG2 A inhibitory receptor on circulating NK cells in patients with β-thalassemia major was remarkably up-regulated, but there were no significant differences in the expression levels of NKP30, NKP46, NKG2 D, CD158 a and IFN-γ. These results indicate NKG2 A inhibitory receptor may play a key role in transfusion-induced immunodepression of NK cells in patients with β-thalassemia major.

A Bronchopulmonary Onset of Candidemia Revealing a Granulomatosis with Polyangiitis

Candidemia is defined as being a yeast infection confirmed by the presence of at least one positive Candida blood culture. It is a life threatening infection causing high mortality. The clinical signs are generally compatible with the causative agent (whether there is a deep venous catheter or not). On the other hand and according to the 2012 Revised Chapel Hill Classification, granulomatosis with polyangiitis GPA is classified as a vasculitis associated with antineutrophil cytoplasmic antibodies ANCA. It is a systemic disease characterized by the anatomopathological aspect of granuloma. We report the case of a patient who presented an atypical and a very rare revealing mode of GPA which was a bronchopulmonary candidiasis complicated by candidemia. Despite its controversy, the combination in the acute phase of antifungal treatment based on intravenous voriconazole and glucocorticoid therapy has made it possible to control candidemia and calm vasculitis.

Protective effects of Wuwei Xiaodu Drink against chronic osteomyelitis through Foxp3^(+)CD25^(+)CD4^(+) Treg cells via the IL-2/STAT5 signaling pathway

To explore the effectiveness and safety of a Chinese medicinal decoction Wuwei Xiaodu Drink(WWXDD)in inhibiting chronic osteomyelitis via regulatory T cells signaling.The effective constitutes of WWXDD and osteomyelitis related genes were screened.Target proteins were cross-validated using the Venny database.GO function and KEGG pathway analysis were performed for target proteins,while pharmacological network was constructed.The bone properties were analyzed by HE staining and the concentrations of immune factors were measured by ELISA.The expression of CTLA-4 and Foxp3 mRNA and STAT5,p-STAT5,CTLA-4 and Foxp3 protein were detected using Real-time PCR and Western blot,respectively.FACS was used to analyze the percentages of cells.A total of 117 genes overlapped between 785 target genes of the active compounds of WWXDD and 912 osteomyelitis related genes.Inflammation-related genes,including IL-6,TNFα,IL-1βand IL-2 showed high connection degree in the drug-compound-disease-target network.GO function and KEGG pathway analysis revealed that 117 intersection genes mainly enriched in virus infection related pathways,immune related pathways and chemokine signaling pathway.Furthermore,the development of chronic osteomyelitis was suppressed in model rats after treatment with WWXDD.Meanwhile,the concentrations of IL-2 and CD4^(+)CD25^(+)Foxp3 Treg perr centages together with the levels of p-STAT5,CTLA-4 and Foxp3 were also down-regulated.Furthermore,IL-2 and WWXDD drug-containing serum exhibited opposite effects on regulating IL-2,IL-10,TGF-β1,Foxp3,CTLA4 and STAT5.In addition,a STAT5 phosphorylation inhibitor suppressed the expression of Foxp3 and CTLA-4.WWXDD can treat chronic osteomyelitis through suppressing the main regulating factors of Tregs and interfere its immunodepression.Our results bring a new solution for chronic osteomyelitis.