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关键词： 自体血回输   剖宫产   产后出血   异体输血需求   凝血功能   细胞免疫功能  

摘要： 目的 分析不同自体血回输方式对剖宫产产后出血患者异体输血需求、凝血功能及细胞免疫功能的影响。方法 选取2022年1月—2024年1月厦门大学附属第一医院诊治的120例剖宫产产后出血患者为研究对象,分为稀释组60例采用稀释式自体血回输,回收组60例采用回收式自体血回输。检测对比两组输凝血成分(血小板、冷沉淀、血浆)、异体血、凝血功能[活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、D-二聚体(D-D)、纤维蛋白原(FIB)]、细胞免疫功能(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、炎性反应[细胞介素-2(IL-2)、白细胞介素-6(IL-6)]、应激指标[去甲肾上腺素(NE)、血管紧张素Ⅱ(AngⅡ)]、电解质(钙、钾、钠)及并发症。结果 与稀释组相比,回收组输血小板、冷沉淀、血浆、异体红细胞占比及并发症发生率较低(P<0.05)。输血前,两组APTT、PT、D-D、FIB、CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)、IL-2、IL-6、NE及AngⅡ水平比较差异无统计学意义(P>0.05);输血后,两组APTT、PT、D-D、CD8^(+)、IL-6、NE、AngⅡ水平降低,且回收组较低,FIB、CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)、IL-2水平升高,且回收组较高(P<0.05)。输血前后,两组钙、钾及钠水平比较差异无统计学意义(P>0.05)。结论 剖宫产产后出血患者应用回收式自体血回输可降低异体输血需求,改善凝血功能,增强免疫功能,缓解炎性、应激反应,且对电解质影响较小,安全性较高。

关键词： T-cells  

摘要： Antigen discovery technologies have largely focused on major histocompatibility complex (MHC) class I-restricted human T cell receptors (TCRs), leaving methods for MHC class II-restricted and mouse TCR reactivities relatively undeveloped. Here we present TCR mapping of antigenic peptides (TCR-MAP), an antigen discovery method that uses a synthetic TCR-stimulated circuit in immortalized T cells to activate sortase-mediated tagging of engineered antigen-presenting cells (APCs) expressing processed peptides on MHCs. Live, tagged APCs can be directly purified for deconvolution by sequencing, enabling TCRs with unknown specificity to be queried against barcoded peptide libraries in a pooled screening context. TCR-MAP accurately captures self-reactivities or viral reactivities with high throughput and sensitivity for both MHC class I-restricted and class II-restricted TCRs. We elucidate problematic cross-reactivities of clinical TCRs targeting the cancer/testis melanoma-associated antigen A3 and discover targets of myocarditis-inciting autoreactive T cells in mice. TCR-MAP has the potential to accelerate T cell antigen discovery efforts in the context of cancer, infectious disease and autoimmunity. T cell-specific antigens are discovered at high throughput without killing target cells.

关键词： CD247   FOXP3   Gene   Methylation   HLA haplotypes  

摘要： Background: Celiac disease is an autoimmune disorder that affects the small intestine in people with gluten intolerance. HLA-DQ2 and DQ8 have been associated with Celiac Disease. CD247 is a subunit of the T cell receptor complex and Forkhead box P3 (FOXP3) is a transcription factor involved in the regulation of the immune response. Expression levels of these two markers in various diseases, including autoimmune disorders, are controversial. In this context, we aimed to shed light on the etiopathogenesis of Celiac disease by determining the methylation profile of CD247 and FOXP3 genes, and to calculate the frequency of HLA-DQ haplotypes in this disease. Methods: Methylated and unmethylated copy numbers of the CD247 and FOXP3 genes in samples were calculated using the methylation-specific qPCR method. The records regarding HLA-DQ2 and DQ8 genotypes previously detected from our patients by Real Time PCR and tissue transglutaminase IgA (TTG-IgA) by ELISA, were analyzed. Results: CD247 methylation rate in our patients was significantly lower than in controls. According to the Marsh classification, the methylation level in Marsh type 2-3 patients was statistically lower than in type 1. On the contrary, FOXP3 had a significantly higher methylation rate in the patient group compared to healthy controls, and this gene was also found to be more methylated in Marsh type 2-3 patients than in Marsh type 1. In the patient group, HLA-DQ2 positivity was 82.5% and HLA-DQ8 positivity was 37.5%. Conclusion: The data suggest that CD247 expression is upregulated, whereas FOXP3 expression is downregulated in Celiac disease. Among HLA haplotypes, HLA-DQ2 heterodimer came to the forefront with its frequency in terms of celiac predisposition.

关键词： Platelet component   Transfusion-associated graft-versus-host dis-   ease   HLA   haplotype  

摘要： Clinical application of pathogen-reduction technology (PRT) is often restricted to platelet and non-cellular components, representing a minor fraction of the overall blood supply. The greatest benefit for patient safety may eventually derive from PRT in red cells, which is still unavailable for routine use. PRT is more effective to inactivate leukocytes than current irradiation, particularly pertinent for Japan with the only universal irradiation of cellular blood components. Elsewhere, only vulnerable patient cohorts are receiving irradiated cellular components. Blood components treated with approved PRT systems are exempt from irradiation if the patient requires irradiated components. Transfusion medicine has a strategic opportunity to develop and eventually utilize PRT for all cellular components, other than hematopoietic progenitor cell products. PRT would then enable leukocyte inactivation for 100 % of the blood supply, beneficial for transfusion safety in all patients.

关键词： experimental autoimmune encephalomyelitis   multiple sclerosis   neuroinflammation   stress granules   T-cell intracellular antigen 1  

摘要： The dysfunction of stress granules (SGs) plays a crucial role in the pathogenesis of various neurological disorders, with T cell intracellular antigen 1 (TIA1) being a key component of SGs. However, the role and mechanism of TIA1-mediated SGs in experimental autoimmune encephalomyelitis (EAE) remain unclear. In this study, upregulation of TIA1, its translocation from the nucleus to the cytoplasm, and co-localization with G3BP1 (a marker of SGs) are observed in the spinal cord neurons of EAE mice. Deletion of TIA1 in the CNS alleviates neuroinflammation, suppresses demyelination and axonal damage, and reduces neuronal loss in EAE mice. Furthermore, alleviation of autophagy dysfunction and reduction of chronic persistent SGs are observed in Tia1Nestin-CKO EAE mice. Mechanistically, IL-31RA levels are decreased in Tia1Nestin-CKO EAE mice, which inhibit the downstream PI3K/AKT signaling pathway associated with IL-31RA, thereby enhancing autophagy and suppressing the NF-kappa B signaling pathway, further alleviating EAE symptoms. Knockdown of TIA1 in primary neurons and N2a cells treated with sodium arsenite also reduces the formation of SGs. These findings reveal an unrecognized role of TIA1-mediated SGs in promoting neuroinflammation and demyelination, offering novel therapeutic targets for MS.

关键词： 17 HLA-related loci   allele frequency   haplotype frequency   linkage disequilibrium  

摘要： Although the allele and haplotype frequencies of 11 HLA loci (HLA-A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPA1 and DPB1) have been reported in different populations, rare studies have simultaneously assessed the allele distributions of non-classical HLA class I genes (HLA-E/F/G/H) and MICA/MICB together with the 11 classical HLA loci, or further analysed the haplotype frequencies covering the 17 loci. The present study aims to investigate the allele diversity and haplotype frequencies of 17 HLA-related loci including HLA genes and MICA/MICB simultaneously using a hybrid capture (HC)-based NGS method. A total of 358 HLA alleles including 177 class I and 137 class II alleles, as well as 29 MICA and 15 MICB alleles were identified in this project. The most frequent alleles at each locus were A*11:01 (29.10%), B*40:01 (14.46%), C*01:02 (19.90%), DRB1*09:01 (15.61%), DQB1*03:01 (18.48%), DPB1*05:01 (40.13%), DQA1*01:02 (22.58%), DPA1*02:02 (55.27%), DRB3*02:02 (65.95%), DRB4*01:03 (95.20%), DRB5*01:01 (75.97%), E*01:03 (62.63%), F*01:01 (97.07%), G*01:01 (70.74%), H*01:01 (35.87%), MICA*010:01 (19.90%) and MICB*005:02 (57.53%), respectively. The haplotype frequencies for different combinations of HLA loci were estimated and linkage disequilibrium (LD) between alleles for all pairs of neighbouring loci were calculated. The most frequent haplotype covering 17 loci was F*01:01-G*01:01-H*01:01-A*02:07-E*01:03-C*01:02-B*46:01-MICA*010:01-MICB*005:02-DRB4*01:03-DRB1*09:01-DQA1*03:02-DQB1*03:03-DPA1*02:02-DPB1*05:01 with a frequency of 3.18%. This is the first study on allelic polymorphism, haplotype inference and LD covering 17 HLA-related loci simultaneously in the Shenzhen Chinese population. These results will extend our knowledge of the allelic diversity of the HLA complex and provide population genetics data for transplantation and HLA-associated disease studies.

关键词： B cells   IgE   IL-17RB   IL-25   type 2 inflammation  

摘要： BackgroundAlarmin cytokine IL-25 promotes type 2 inflammatory responses in disorders such as asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and known targets include ILC2 and Th2 cells. However, other cellular targets for IL-25 remain poorly *** investigate induction and expression of IL-25 receptor (IL-17RB) by B cells and evaluate responsiveness of IL-17RB-expressing B cells to IL-25 in ***-17RB expression, regulation and function on B cells were evaluated in peripheral blood-derived B cells by flow cytometry and RT-PCR, including in response to IgE-inducing stimuli (anti-CD40 mAb and IL-4). Single-cell RNA sequencing was used to compare IL-17RB+ and IL-17RB-activated peripheral blood-derived B cells. To evaluate B cell IL-17RB expression within type 2 inflamed tissue, B cells were compared from nasal polyps, control turbinate tissue and matched peripheral *** of B cells with anti-CD40 and IL-4 increased IL-17RB expression at both protein and mRNA level, which was further upregulated by IL-25. B cells induced to express IL-17RB responded to IL-25 with enhanced antibody production. Single-cell RNA-sequencing showed that IL17RB+ activated B cells expressed higher levels of IGHE, CCL17 and CCL22 compared to IL17RB- B cells. B cells from nasal polyp tissue expressed higher levels of surface IL-17RB compared with control tissue, correlating with patient-reported CRSwNP severity (SNOT-22).ConclusionPeripheral blood B cells activated under IgE-inducing conditions express surface IL-17RB, and tissue IL-17RB+ B cells are increased in type 2 inflammation. IL-17RB+ cells have a distinct transcriptional profile and respond to IL-25 with enhanced antibody production, highlighting the IL-25/IL-17RB pathway as a potential therapeutic target for CRSwNP and other type 2 inflammatory disorders.

关键词： anti-HLA antibodies   cardiovascular evaluation   coronary artery disease   HLA mismatch   host versus graft antibodies   lung transplantation   revascularization   transplant candidate selection  

摘要： AimsCoronary artery disease (CAD) is a frequent comorbidity in lung transplant (LuTx) candidates. The impact of allogenic organ transplantation and the corresponding alterations in immune response on the progression of CAD remains poorly understood. In this study, we sought to analyze the effect of donor-recipient overall human leukocyte antigen (HLA) and HLA-DQ mismatch on cardiovascular outcomes following *** and ResultsThis retrospective analysis of adult patients receiving lung transplantation at the LMU University Hospital between 2012 and 2018 included 310 patients, the majority of whom (67.4%) had undergone double lung transplantation. There were no significant differences in the incidence of the primary composite endpoint between patients with high/low HLA mismatches (22 [7.9%] vs. 4 [12.9%];p = 0.311). Numerically higher rates of the primary endpoint, myocardial infarction, and cardiovascular death in the low HLA mismatch group can partially be explained by differences in baseline rates of CAD and coronary sclerosis. Notably, neither HLA-DQ mismatch nor the occurrence of rejection episodes or cytomegalovirus (CMV) infection was associated with the occurrence of cardiovascular events following *** this study cohort, high HLA mismatch and HLA-DQ mismatch were not associated with increased adverse cardiovascular events. Furthermore, neither transplant rejection nor CMV infection increased the risk for cardiovascular events. The high cardiovascular event rates following LuTx necessitate meticulous cardiovascular follow-up, irrespective of immunological matching.

关键词： Inflammatory bowel disease   Intestinal T cells   Mucosal immunology   ex-Th17   IL-12  

摘要： CD4+ memory T cell (TM) reactivation drives chronicity in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis. Defects driving loss of TM regulation likely differ between patients but remain undefined. In health, approximately 40 % of circulating gut-homing CD38+TM express co-inhibitory receptor Tcell immunoreceptor with immunoglobulin and ITIM domains (TIGIT). TIGIT+CD38+TM have regulatory function while TIGITnegCD38+TM are enriched in IFN-gamma-producing cells. We hypothesized TIGITnegCD38+TM are inflammatory and drive disease in a subgroup of IBD patients. We characterized TIGIT+CD38+TM in a uniquely large cohort of pediatric IBD patients from time of diagnosis into adulthood. Circulating TIGITnegCD38+TM frequencies were higher in a subgroup of therapy-na & iuml;ve CD patients with high plasma IFN-gamma and a more severe disease course. TIGITnegCD38+TM were highly enriched in HLA-DR+ and ex-Th17/Th1-like cells, high producers of IFN-gamma. Cultures of healthy-adult-stimulated TM identified IL-12 as the only IBD-related inflammatory cytokine to drive the pathogenic ex-Th17-TIGITnegCD38+ phenotype. Moreover, IL12RB2 mRNA expression was higher in TIGITnegCD38+TM than TIGIT+CD38+TM, elevated in CD biopsies compared to controls, and correlated with severity of intestinal inflammation. Overall, we argue that in a subgroup of pediatric CD, increased IL-12 signaling drives reprogramming of Th17 to inflammatory Th1-like TIGITnegCD38+TM and causes more severe disease.