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Background and Objectives: Anti‐E alloantibody is the most common and important red blood cell (RBC) alloantibody during pregnancy. The study aimed to determine the correlation between RhE alloimmunization and human leukocyte antigen (HLA) allele polymorphism, as well as haplotype diversity, among pregnant individuals in the Chinese Han population. Study Design and Methods: All individuals included in our study were RhE‐negative pregnant women of Chinese Han ethnicity, confirmed through serological testing. Pregnancy could be the only potential stimulating factor in RBC alloimmunization. Given the serological testing, the participants were divided into anti‐E (responders) and non‐anti‐E‐producing group (non‐responders). The class I and II classical HLA genotyping were determined using next‐generation sequencing, and the HLA genotype and haplotype frequencies were compared between the responders and non‐responders. Results: In total, 76 responders and 94 non‐responders were enrolled in this study. Comparison results showed that all HLA class I alleles had no difference between the two groups. For HLA class II phenotypes, responders had higher frequencies of HLA‐DRB1*09:01, HLA‐DQA1*03:02 and HLA‐DQB1*03:03 phenotypes than non‐responders, and the differences were statistically significant (pc < 0.05). In addition, the haplotype frequency of HLA‐DRB1*09:01‐DQA1*03:02‐DQB1*03:03 in the RhE responders was significantly higher than in the non‐responders (31.58% vs. 12.77%; odds ratio, 3.154; 95% confidence interval, 1.823–5.456; pc value, 1.25 × 10−3). Conclusion: Our findings indicated that HLA‐DRB1*09:01, HLA‐DQA1*03:02 and HLA‐DQB1*03:03 might be susceptible alleles for RhE alloimmunization among Chinese Han pregnant females. These three susceptible alleles constituted the unique three‐locus haplotype in the RhE responders and collaborated to RhE alloimmunization. [ABSTRACT FROM AUTHOR]

The aetiological mechanism of preeclampsia (PE) is unclear exactly, so we attempted to investigate the association between susceptibility to preeclampsia and renin-angiotensin-aldosterone system (RAAS) gene polymorphisms to explore the aetiology in terms of genetics. A systematic search was performed in electronic databases to identify relevant studies. Eventually 73 studies were enrolled, odds ratios were generated by 5 genetic models. In overall analysis, significant associations were detected for AGT M235T, AT1R A1166C and CYP11B2 C344T whereas negative correlation was shown for AGT T174M. As stratified by race and geography, AGT 235T allele and AT1R 1166C allele increased preeclampsia risk and AGT T174M was justified uncorrelated with preeclampsia. Our meta-analysis illustrated that AGT 235T allele and AT1R 1166C allele increased and CYP11B2 344T allele decreased preeclampsia risk while AGT T174M polymorphism did not change preeclampsia risk. Hence, pregnant women carrying high-risk genotypes need strengthened management to prevent and early identification of preeclampsia. [ABSTRACT FROM AUTHOR]

Background and Objectives: To advance blood transfusion safety, the Chinese Haemovigilance Network (CHN) was put into operation in 2018. This report describes the development of the CHN and evaluates its role by analysing reported adverse transfusion reactions (ATRs) from 2018 to 2020. Materials and Methods: All data in this study were obtained from the CHN online reporting platform. A timeline of CHN development is presented, and the activities of CHN‐enrolled facilities are analysed by year. The reported ATRs were analysed in detail for ATR types, blood components involved and adherence to case definition, severity and imputability criteria. Incidence rates were calculated and compared with international examples. Results: During 2018–2020, a total of 3061 ATRs were reported through the CHN online reporting system. The rate of reported ATRs in all facilities and the 10 highest reporting facilities was 0.7‰ and 1.8‰, respectively. When analysed by year, the incidence rate showed an increasing trend from 2018 to 2020. Allergic (68.2%) and febrile non‐haemolytic transfusion reaction (27.1%) were the most common. The vast majority of ATRs (92.0%) were not serious, but serious cases of transfusion‐associated circulatory overload, transfusion‐associated dyspnoea and hypotensive reaction were common. Most (86.0%) of reported cases were definitely or probably associated with transfusion. Conclusion: Under‐reporting of ATRs occurs in many Chinese hospitals, but the establishment of CHN has increased ATR recognition and management. More effort will be needed in the future to detect transfusion problems and improve transfusion practice in China. [ABSTRACT FROM AUTHOR]

Background and objectives: Haemovigilance involves surveillance of the whole chain of blood transfusion with the aim of identifying adverse events and errors and improving outcomes for patients. The Chinese Haemovigilance Network, founded in August 2017, has witnessed a rapid development in the last three years. Materials and methods: Based on the 1,022 cases in 2019, we analysed the adverse reactions (ARs) by blood component, clinical outcome severity and demography of recipients in an effort to publish the first annual Chinese haemovigilance report. Results: The AR rate associated with blood transfusion in 2019 was 0·2% in China. Allergic reactions and FNHTR were the two most common adverse symptoms, accounting for 97·7% of the reports. Two‐thirds of the TAD, AHTR and TACO and all of the HTR and DHTR resulted in hospitalization or prolongation of hospitalization. Plasma and AP were usually associated with allergic reaction (81·1%), whereas red cells more commonly cause FNHTR (68·8%) and all the AHTR, HTR, DSTR and DHTR. 84·1% of patients were aged 16 years or over, and the majority of the TAD, AHTR, TACO and HTR involved patients aged 60 and above. The ratio of serious adverse reactions (SARs) was 8·2%. Allergic reaction and FNHTR were top two (85·7%) SARs. The first case related to anti‐D immunoglobulin was detected in a DHTR report. Conclusion: This report provides the world's first overview of transfusion‐related adverse reactions in China. This report is useful for better understanding transfusion risks in China. [ABSTRACT FROM AUTHOR]

Seven exons of the I ABO i gene were amplified and direct-sequenced as the method previously reported.[1] The haplotype of the I ABO i gene was identified by clone-sequencing (PMD18-T vector, Tiangen Biotech Co.). Keywords: blood group genomics EN blood group genomics E10 E11 2 03/23/23 20230301 NES 230301 The ABO system is the most important blood system in transfusion medicine, which contains four major ABO phenotypes: A, B, O, and AB. Recently, we identified a novel missense variant in the exon 7 of the I ABO i gene in a Tibetan woman with the B SB el sb phenotype. [Extracted from the article]

Background: Transfusion-related acute lung injury (TRALI) is one of the most serious adverse events following transfusion, and there is no specific treatment in clinical practice. However, regulatory T cells (Tregs) have been suggested to play a potential role in the treatment of TRALI. This study investigated whether interleukin (IL)-2 or IL-2/anti-IL-2 complexes (IL-2c), which are mediators of Treg expansion, can modulate the severity of antibody-mediated TRALI in vivo.Study Design and Methods: This study utilized a mouse model of the "two-hit" mechanism: BALB/c mice were primed with lipopolysaccharide (LPS) as the first hit, and then TRALI was induced by injecting major histocompatibility complex Class I antibodies. Mice injected with LPS only or LPS combined with isotype control antibodies served as controls. For the Treg-depleted groups, mice were infused with anti-mouse IL-2Rα first and then subjected to the same treatments as the TRALI group. Regarding IL-2- and IL-2c-treated mice, recombinant murine IL-2 or IL-2c was intraperitoneally administered to mice for 5 consecutive days before induction of the TRALI model. Samples were collected 2 hours after TRALI induction.Results: Prophylactic administration of IL-2 or IL-2c to mice prevented the onset of edema, pulmonary protein levels, and proinflammatory factors that inhibited polymorphonuclear neutrophil aggregation in the lungs. Furthermore, the percentage of CD4+ CD25+ FoxP3+ Tregs was expanded in vivo using IL-2 and IL-2c compared to TRALI mice, as was confirmed through analysis of the spleen, blood, and lung.Conclusion: This study validates that the protective mechanisms against TRALI involve CD4+ CD25+ FoxP3+ Tregs, which can be expanded in vivo by IL-2 and IL-2c. This results in increased IL-10 levels and decreased IL-17A, thereby prophylactically preventing antibody-mediated murine TRALI. [ABSTRACT FROM AUTHOR]

Background: This study measured the serum levels of complement component (C)3a and C5a and the placental expressions of C3a receptor (R) and C5aR to determine a potential correlation with circulating angiotensin II type 1 (AT1) receptor agonistic autoantibody (AT1-AA) in severe pre-eclampsia.Methods: A total of 118 women were recruited and divided into 2 groups: the control group (normotensive preterm pregnancies, n = 66) and severe pre-eclampsia group (n = 52). Levels of C3a, C5a and AT1-AA in serum were measured by enzyme-linked immunosorbent assay and C3aR and C5aR in placenta by Western blotting.Results: Levels of C3a, C5a and AT1-AA in serum from the severe pre-eclampsia group were significantly higher than in controls (p < 0.05). Placental expression of C3aR and C5aR in the pre-eclampsia group was lower than that in controls (p < 0.05). There were significant positive correlations between levels of C3a, C5a and AT1-AA in serum from the pre-eclampsia group (p < 0.05). In contrast, there was no correlation between C3aR and C5aR in the placenta and AT1-AA in serum in the pre-eclampsia group (p > 0.05).Conclusion: Increased C3a, C5a and AT1-AA in the serum provide indirect evidence that AT1-AA-mediated activation contributes to activate complement, which is a key mechanism underlying the pathogenesis of severe pre-eclampsia. [ABSTRACT FROM AUTHOR]

Background and Objectives Study Design and Methods Results Conclusion Accurate human leucocyte antigen (HLA) and human platelet antigen (HPA) typing is essential for establishing a blood platelet donor bank to deal with refractoriness in patients undergoing multiple platelet transfusions. Current methods, such as Sanger and next‐generation sequencing, encounter difficulties in haplotyping. Herein, the aim of this study was to establish a method for HLA and HPA typing based on the long read sequencing.The HPA and HLA class I genotypes of 268 platelet donors from the Taiyuan Blood Center, China were identified using long‐read sequencing on the PacBio platform. Allele frequencies for HPA systems and HLA class I genes were calculated, and genetic variability within HPA system genes was analysed.Polymorphisms were identified in 8 of the 35 HPA systems (HPA‐1 to HPA‐6w, HPA‐15 and HPA‐21w), with the frequencies of the ‘b’ allele at 0.0187, 0.0709, 0.4086, 0.0075, 0.0149, 0.0317, 0.4310 and 0.0019, respectively. The alleles with the highest frequencies at the HLA‐A, HLA‐B and HLA‐C loci are HLA‐A02:01, B51:01, B46:01 and C06:02, respectively. Additionally, several genetic patterns in HPA systems were identified, including the c.166‐1029C>T variant, which was found exclusively in samples carrying the HPA‐1b allele.This study developed a targeted long‐read sequencing method characterized by high throughput and simultaneity, capable of resolving allele ambiguities for effective HLA class I genotyping in establishing a platelet donor bank. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) is a highly aggressive type of lung cancer with poor responses to traditional therapies such as surgery, radiotherapy, and chemotherapy. While immunotherapy has become an effective approach for treating multiple types of cancer, solid tumors frequently exhibit immune escape through various mechanisms, including downregulation of MHC I expression. However, whether the upregulation of MHC I expression can improve the immunotherapeutic effect on NSCLC remains unexplored. Suberoylanilide hydroxamic acid (SAHA) is a potent histone deacetylase (HDAC) inhibitor that has been applied clinically to treat lymphoma, but a high dose of SAHA kills tumor cells and normal cells without preference. Here, we report that low-dose SAHA enhances CD8+ T cell-mediated antitumor immunity by upregulating MHC I expression in NSCLC cells.Flow cytometric analysis, quantitative real-time PCR and western blot were used to analyze the expression of MHC I, STAT1 and Smad2/3 in both human and mouse NSCLC cell lines after SAHA treatment. The nuclear translocation of phosphorylated STAT1 and Smad2/3 was investigated by western blot and immunofluorescence staining. The mechanisms underlying STAT1 and Smad2/3 upregulation were analyzed through database searches and chromatin immunoprecipitation-qPCR. Finally, we assessed the antitumor effect of specific CD8+ T cells with SAHA treatment in vivo and in vitro.We showed that low-dose SAHA upregulated the expression of MHC I in NSCLC cell lines without affecting cell viability. We also provided evidence that high levels of MHC I induced by SAHA promoted the activation, proliferation, and cytotoxicity of specific CD8+ T cells in mouse models. Mechanistically, low-dose SAHA increased the levels of H3K9ac and H3K27ac in the promoters of the STAT1, Smad2 and Smad3 genes in NSCLC cells by inhibiting HDAC activity, resulting in elevated expression levels of STAT1, Smad2 and Smad3. The nuclear translocation of phosphorylated STAT1 and Smad2/3 markedly upregulated the expression of MHC I in NSCLC cells.Low-dose SAHA enhances CD8+ T cell-mediated antitumor immunity by boosting MHC I expression in NSCLC cells. Thus, we revealed a key mechanism of SAHA-mediated enhanced antitumor immunity, providing insights into a novel immunotherapy strategy for NSCLC.Methods: Non-small cell lung cancer (NSCLC) is a highly aggressive type of lung cancer with poor responses to traditional therapies such as surgery, radiotherapy, and chemotherapy. While immunotherapy has become an effective approach for treating multiple types of cancer, solid tumors frequently exhibit immune escape through various mechanisms, including downregulation of MHC I expression. However, whether the upregulation of MHC I expression can improve the immunotherapeutic effect on NSCLC remains unexplored. Suberoylanilide hydroxamic acid (SAHA) is a potent histone deacetylase (HDAC) inhibitor that has been applied clinically to treat lymphoma, but a high dose of SAHA kills tumor cells and normal cells without preference. Here, we report that low-dose SAHA enhances CD8+ T cell-mediated antitumor immunity by upregulating MHC I expression in NSCLC cells.Flow cytometric analysis, quantitative real-time PCR and western blot were used to analyze the expression of MHC I, STAT1 and Smad2/3 in both human and mouse NSCLC cell lines after SAHA treatment. The nuclear translocation of phosphorylated STAT1 and Smad2/3 was investigated by western blot and immunofluorescence staining. The mechanisms underlying STAT1 and Smad2/3 upregulation were analyzed through database searches and chromatin immunoprecipitation-qPCR. Finally, we assessed the antitumor effect of specific CD8+ T cells with SAHA treatment in vivo and in vitro.We showed that low-dose SAHA upregulated the expression of MHC I in NSCLC cell lines without affecting cell viability. We also provided evidence that high levels of MHC I induced by SAHA promoted the activation, proliferation, and cytotoxicity of specific CD8+ T cells in mouse models. Mechanistically, low-dose SAHA increased the levels of H3K9ac and H3K27ac in the promoters of the STAT1, Smad2 and Smad3 genes in NSCLC cells by inhibiting HDAC activity, resulting in elevated expression levels of STAT1, Smad2 and Smad3. The nuclear translocation of phosphorylated STAT1 and Smad2/3 markedly upregulated the expression of MHC I in NSCLC cells.Low-dose SAHA enhances CD8+ T cell-mediated antitumor immunity by boosting MHC I expression in NSCLC cells. Thus, we revealed a key mechanism of SAHA-mediated enhanced antitumor immunity, providing insights into a novel immunotherapy strategy for NSCLC.Results: Non-small cell lung cancer (NSCLC) is a highly aggressive type of lung cancer with poor responses to traditional therapies such as surgery, radiotherapy, and chemotherapy. While immunotherapy has become an effective approach for treating multiple types of cancer, solid tumors frequently exhibit immune escape through various mechanisms, including downregulation of MHC I expression. However, whether the upregulation of MHC I expression can improve the immunotherapeutic effect on NSCLC remains unexplored. Suberoylanilide hydroxamic acid (SAHA) is a potent histone deacetylase (HDAC) inhibitor that has been applied clinically to treat lymphoma, but a high dose of SAHA kills tumor cells and normal cells without preference. Here, we report that low-dose SAHA enhances CD8+ T cell-mediated antitumor immunity by upregulating MHC I expression in NSCLC cells.Flow cytometric analysis, quantitative real-time PCR and western blot were used to analyze the expression of MHC I, STAT1 and Smad2/3 in both human and mouse NSCLC cell lines after SAHA treatment. The nuclear translocation of phosphorylated STAT1 and Smad2/3 was investigated by western blot and immunofluorescence staining. The mechanisms underlying STAT1 and Smad2/3 upregulation were analyzed through database searches and chromatin immunoprecipitation-qPCR. Finally, we assessed the antitumor effect of specific CD8+ T cells with SAHA treatment in vivo and in vitro.We showed that low-dose SAHA upregulated the expression of MHC I in NSCLC cell lines without affecting cell viability. We also provided evidence that high levels of MHC I induced by SAHA promoted the activation, proliferation, and cytotoxicity of specific CD8+ T cells in mouse models. Mechanistically, low-dose SAHA increased the levels of H3K9ac and H3K27ac in the promoters of the STAT1, Smad2 and Smad3 genes in NSCLC cells by inhibiting HDAC activity, resulting in elevated expression levels of STAT1, Smad2 and Smad3. The nuclear translocation of phosphorylated STAT1 and Smad2/3 markedly upregulated the expression of MHC I in NSCLC cells.Low-dose SAHA enhances CD8+ T cell-mediated antitumor immunity by boosting MHC I expression in NSCLC cells. Thus, we revealed a key mechanism of SAHA-mediated enhanced antitumor immunity, providing insights into a novel immunotherapy strategy for NSCLC.Conclusions: Non-small cell lung cancer (NSCLC) is a highly aggressive type of lung cancer with poor responses to traditional therapies such as surgery, radiotherapy, and chemotherapy. While immunotherapy has become an effective approach for treating multiple types of cancer, solid tumors frequently exhibit immune escape through various mechanisms, including downregulation of MHC I expression. However, whether the upregulation of MHC I expression can improve the immunotherapeutic effect on NSCLC remains unexplored. Suberoylanilide hydroxamic acid (SAHA) is a potent histone deacetylase (HDAC) inhibitor that has been applied clinically to treat lymphoma, but a high dose of SAHA kills tumor cells and normal cells without preference. Here, we report that low-dose SAHA enhances CD8+ T cell-mediated antitumor immunity by upregulating MHC I expression in NSCLC cells.Flow cytometric analysis, quantitative real-time PCR and western blot were used to analyze the expression of MHC I, STAT1 and Smad2/3 in both human and mouse NSCLC cell lines after SAHA treatment. The nuclear translocation of phosphorylated STAT1 and Smad2/3 was investigated by western blot and immunofluorescence staining. The mechanisms underlying STAT1 and Smad2/3 upregulation were analyzed through database searches and chromatin immunoprecipitation-qPCR. Finally, we assessed the antitumor effect of specific CD8+ T cells with SAHA treatment in vivo and in vitro.We showed that low-dose SAHA upregulated the expression of MHC I in NSCLC cell lines without affecting cell viability. We also provided evidence that high levels of MHC I induced by SAHA promoted the activation, proliferation, and cytotoxicity of specific CD8+ T cells in mouse models. Mechanistically, low-dose SAHA increased the levels of H3K9ac and H3K27ac in the promoters of the STAT1, Smad2 and Smad3 genes in NSCLC cells by inhibiting HDAC activity, resulting in elevated expression levels of STAT1, Smad2 and Smad3. The nuclear translocation of phosphorylated STAT1 and Smad2/3 markedly upregulated the expression of MHC I in NSCLC cells.Low-dose SAHA enhances CD8+ T cell-mediated antitumor immunity by boosting MHC I expression in NSCLC cells. Thus, we revealed a key mechanism of SAHA-mediated enhanced antitumor immunity, providing insights into a novel immunotherapy strategy for NSCLC. [ABSTRACT FROM AUTHOR]

Background: Transfusion-related acute lung injury (TRALI) is one of the most serious adverse events following transfusion, and there is no specific treatment in clinical practice. However, regulatory T cells (Tregs) have been suggested to play a potential role in the treatment of TRALI. This study investigated whether interleukin (IL)-2 or IL-2/anti-IL-2 complexes (IL-2c), which are mediators of Treg expansion, can modulate the severity of antibody-mediated TRALI in vivo., Study Design and Methods: This study utilized a mouse model of the "two-hit" mechanism: BALB/c mice were primed with lipopolysaccharide (LPS) as the first hit, and then TRALI was induced by injecting major histocompatibility complex Class I antibodies. Mice injected with LPS only or LPS combined with isotype control antibodies served as controls. For the Treg-depleted groups, mice were infused with anti-mouse IL-2Rα first and then subjected to the same treatments as the TRALI group. Regarding IL-2- and IL-2c-treated mice, recombinant murine IL-2 or IL-2c was intraperitoneally administered to mice for 5 consecutive days before induction of the TRALI model. Samples were collected 2 hours after TRALI induction., Results: Prophylactic administration of IL-2 or IL-2c to mice prevented the onset of edema, pulmonary protein levels, and proinflammatory factors that inhibited polymorphonuclear neutrophil aggregation in the lungs. Furthermore, the percentage of CD4 + CD25 + FoxP3 + Tregs was expanded in vivo using IL-2 and IL-2c compared to TRALI mice, as was confirmed through analysis of the spleen, blood, and lung., Conclusion: This study validates that the protective mechanisms against TRALI involve CD4 + CD25 + FoxP3 + Tregs, which can be expanded in vivo by IL-2 and IL-2c. This results in increased IL-10 levels and decreased IL-17A, thereby prophylactically preventing antibody-mediated murine TRALI., (© 2018 AABB.)