Extracellular vesicles (EVs) are small, double-membrane vesicles derived from erythrocytes, leukocytes, platelets, and cells of multiple tissues under physiologic or pathologic conditions. The role of EVs in stored RBC units is of great interest with respect to transfusion-related immunomodulation. The current study focuses on the quantity of EVs isolated from stored RBC units and their action on B cell-mediated immune responses. The in vitro experiment demonstrated that EVs exhibited a negative role in B cell survival, plasmacytic differentiation, and class switch recombination under LPS stimulation. Furthermore, LPS-induced antibody production was significantly decreased after EVs injection in vivo. Biochemical analysis revealed that EVs hampered the expression of Blimp-1 and IRF4 and the activation of NF-B pathway in LPS-primed B cells. Overall, these data imply a vital role for EVs isolated from RBC units in B cell-mediated immune responses.
Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease mediated by antibodies against the patient’s red blood cells. However, the underlying mechanisms for antibody production are not fully understood. Previous studies of etiology and pathogenesis of AIHA mainly focus on autoreactive B cells that have escaped tolerance mechanisms. Few studies have reported the function of TFH and TFR cells in the process of AIHA. The present study aimed to explore the potential mechanism of TFH and TFR cells in the pathogenesis of AIHA. With the model of murine AIHA, increased ratios of TFH:TFR, elevated serum IL-21 and IL-6 levels, and upregulated Bcl-6 and c-Maf expression were reported. Also, adoptive transfer of purified CD4+CXCR5+CD25- T cells from immunized mice promoted the induction of autoantibody in the AIHA mouse model. Altogether, our data demonstrate the important role of TFH cells for control and induction of AIHA. In the light of the key contributions of TFH cells to the immune response in AIHA, strategies aimed at inhibiting the TFH development or function should be emphasized.
Despite the prognostic value of IDH and other gene mutations found in diffuse glioma, markers that judge individual prognosis of patients with diffuse lower‐grade glioma (LGG) are still lacking. This study aims to develop an expression‐based microRNA signature to provide survival and radiotherapeutic response prediction for LGG patients. MicroRNA expression profiles and relevant clinical information of LGG patients were downloaded from The Cancer Genome Atlas (TCGA; the training group) and the Chinese Glioma Genome Atlas (CGGA; the test group). Cox regression analysis, random survival forests‐variable hunting (RSFVH) screening and receiver operating characteristic (ROC) were used to identify the prognostic microRNA signature. ROC and TimeROC curves were plotted to compare the predictive ability of IDH mutation and the signature. Stratification analysis was conducted in patients with radiotherapy information. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore the biological function of the signature. We identified a five‐microRNA signature that can classify patients into low‐risk or high‐risk group with significantly different survival in the training and test datasets ( P < 0.001). The five‐microRNA signature was proved to be superior to IDH mutation in survival prediction (AUCtraining = 0.688 vs 0.607). Stratification analysis found the signature could further divide patients after radiotherapy into two risk groups. GO and KEGG analyses revealed that microRNAs from the prognostic signature were mainly enriched in cancer‐associated pathways. The newly discovered five‐microRNA signature could predict survival and radiotherapeutic response of LGG patients based on individual microRNA expression.
IntroductionThrombotic thrombocytopenic purpura (TTP) is a rare life‐threatening thrombotic microangiopathy. Therapeutic plasma exchange (TPE) is the first‐line treatment for TTP. In our institution, albumin plus plasma (fresh frozen plasma [FFP] and/or cryoprecipitate‐reduced plasma [CRP]) has been used as replacement fluid since 2014. We aimed to evaluate the efficacy of albumin combined with plasma as TPE for TTP.Material and MethodsWe retrospectively evaluated 20 patients admitted to our institution due to an acute episode of TTP between January 1, 2014 and February 1, 2019. They were divided into two groups according to the replacement fluid protocols: (a) albumin plus FFP (1:1) and (b) albumin plus mixed plasma [ie, albumin and FFP with CRP (2:1:1)] groups. Data on patient characteristics, replacement parameters, outcome, and hemorrhage risk were collected and analyzed.ResultsThere were no significant differences in treatment outcomes between the two groups (P > .05). However, the albumin plus mixed plasma group tended to require fewer plasma exchanges (median, 4) and shorter time to response (median, 15 days) compared to albumin plus FFP group (median, 6; 31 days). Although the cumulative survival of the albumin plus mixed plasma group was higher than the other group starting from day 23 after treatment, we did not observe significant difference (P = .50). No significant increase in the risk for hemorrhage was observed in either group.ConclusionsThe therapeutic efficacy of albumin and mixed plasma (2:1:1) is not inferior to that of albumin and FFP (1:1), and it can be used in treating TTP.
Transfusion of aged erythrocytes is associated with increased morbidity and mortality in the critically infections with incompletely understood mechanism. Previous studies suggested red blood cell (RBC)-derived extracellular vesicles (EVs) may be potential risk factors for the occurrence of transfusion-related immunomodulation (TRIM). The purpose of our study is to evaluate the effects of EVs under the inflammation condition and explore the underlying mechanisms. In vivo, the activity of EVs was evaluated in the caecal ligation and puncture (CLP)-induced sepsis. Our results showed EVs significantly aggravated the inflammatory response of sepsis in serum and lung tissue by promoting the production of pro-inflammatory factors, TNF-α, IL-6, IL-1β, and reduced the survival rate of septic mice in vivo. Importantly, adoptive transfer EVs pretreated bone marrow-derived macrophages (BMDM) obviously aggravated the systemic pro-inflammatory factors in mice after CLP surgery. In vitro, the pro-inflammatory properties of EVs were shown as elevating the levels of TNF-α, IL-6, IL-1βin LPS-stimulated BMDM. Moreover, EVs promoted the LPS-induced macrophages polarization into pro-inflammatory phenotype. The underlying mechanism was possibly that EVs could up-regulate NF-κB and MAPKs activity to favor macrophage cytokines production.
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