The influence of HLA allele and haplotype on RhE alloimmunization among pregnant females in the Chinese Han population.

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.

Plasma transfusion in critically Ill patients with abnormal coagulation tests before invasive procedures: A propensity-adjusted cohort study.

OBJECTIVE: To evaluate the association between plasma transfusion and bleeding complications in critically ill patients with an elevated international normalized ratios undergoing invasive procedures. METHODS: A retrospective study was conducted to evaluate a consecutive sample of critically ill adult patients undergoing invasive procedures (N = 487) with an international normalized ratio ≥ 1.5 between January 1, 2019 and December 31, 2019. Among the followed patients, 125 were excluded due to incomplete case records and 362 were finally included in this investigation. The exposure was whether plasma had been transfused within 24 h before the invasive procedure. The primary outcome was the occurrence of postprocedural bleeding complications. Secondary outcomes included transfusion of red blood cells within 24 h of the invasive procedure, and additional patient-important outcomes such as mortality and length of stay. Tests were performed with univariate and propensity-matched analyses. RESULTS: Of the 362 study participants, 99 (27.3 %) received a preprocedural plasma transfusion. In the propensity score-matched analysis, the rate of the occurrence of postprocedural bleeding complications between two groups was not statistically different (OR, 0.605[95 % CI, 0.341-1.071]; P = .085). The rate of postoperative red blood cell transfusion in the plasma transfusion group was higher than that in the non-plasma transfusion group (35.5 % vs 21.5 %; P < .05). No statistically significant difference in mortality was observed between the two groups (29.0 % vs 31.6 %; P = .101). CONCLUSIONS: Prophylactic plasma transfusion failed to reduce postprocedural bleeding complications in ill critically patients with a coagulopathy. Meanwhile, it was associated with increased red blood cell transfusion after invasive procedures. Findings suggest that abnormal preprocedural international normalized ratios should be managed more conservatively.

Pertinence between risk of preeclampsia and the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms: an updated meta-analysis based on 73 studies.

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.

Differential expression of exosomal microRNAs in fresh and senescent apheresis platelet concentrates.

Patients have a high risk of suffering adverse reactions after receiving platelet products stored for 5 days. Bioactive exosomes in platelet products can be accumulated during storage, which is associated with adverse reactions. MicroRNAs are one of the critical cargoes in exosomes, which participate in cell differentiation, metabolism, and immunomodulation. This study intends to elucidate and analyze the differential expression of exosomal microRNAs in apheresis platelet concentrates during storage and predict the potential functions of target genes. Apheresis platelet concentrates were used to isolate exosomes by ultracentrifugation. Exosomes were phenotyped by western blot, transmission electron microscopy, and nano flow cytometry. The differential expression of the exosomal microRNAs was obtained by a microarray test using four bags of apheresis platelets stored for 5 days compared with 1 day. The differentially expressed microRNAs between the two time points were identified, and their target genes were analyzed by miRWalk and miRDB. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the target genes' functions. Fifteen bags of apheresis platelet concentrates stored for 1 day and 5 days were used to verify the microarray results by quantitative reverse transcription-polymerase chain reactions (qRT-PCR). There were 134 microRNAs in total expressed differently in the two groups (day 1 and day 5), with 57 microRNAs up-regulated and 77 down-regulated (|fold change| > 2.0 and P < .05). Thirteen up-regulated microRNAs (hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-21-5p, hsa-miR-23a-3p, hsa-miR-320b, hsa-let-7a-5p, hsa-miR-25-3p, hsa-miR-126-3p, hsa-miR-320c, hsa-miR-342-3p, hsa-miR-320d, hsa-miR-328-3p, and hsa-miR-320e) detected in all samples were selected to validate the results. The qRT-PCR results showed that five (hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-21-5p, hsa-miR-23a-3p, and hsa-miR-320b) of them were increased more than 10-fold (P < .001); four (hsa-let-7a-5p, hsa-miR-25-3p, hsa-miR-126-3p, hsa-miR-320c) more than five-fold (P < .001); two (hsa-miR-342-3p and hsa-miR-320d) more than two-fold (P < .05); and two (hsa-miR-328-3p and hsa-miR-320e) more than two-fold (P > .05). Specifically, hsa-miR-22-3p increased 14.6-fold; hsa-miR-223-3p increased 13.0-fold; and hsa-miR-21-5p increased 12.0-fold. Based on bioinformatics functional analysis, target genes of top nine microRNAs (hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-21-5p, hsa-miR-23a-3p, hsa-miR-320b, hsa-let-7a-5p, hsa-miR-25-3p, hsa-miR-126-3p, and hsa-miR-320c) were annotated with positive regulation of cell proliferation and nervous system development, and mainly enriched in regulating pluripotency of stem cells signaling pathway, prolactin signaling pathway, and FoxO signaling pathway, etc. The prolactin, FoxO, ErbB, and TNF signaling pathway were relevant to immunomodulation. In particular, hsa-miR-22-3p expression was the most different during storage, with a fold change of 14.6, which might be a key mediator.

What is the context? Platelet transfusion is a widely used clinical treatment, but it is not totally safe. Side effects may happen to patients who receive the "older" platelet products. Exosomes in platelet products can be transfused to patients while receiving blood. Exosomes are accumulated in platelet products during storage. MicroRNAs are one of the important cargoes in exosomes, which can be delivered to the target cells, thus affecting their functions.This study aims to investigate and analyze the differential expression profiling of exosomal microRNAs in apheresis platelet concentrates during storage, and predict the potential function of the target genes. We found out the top nine differentially expressed microRNAs got involved in positive regulation of cell proliferation and nervous system development, and mainly enriched in regulating pluripotency of stem cells signaling pathway, prolactin signaling pathway, and FoxO signaling pathway, etc.What's new? Our study is the first one to test the exosomal microRNAs in the apheresis platelet concentrates. The apheresis platelet concentrates were stored for 1 day and 5 days. Compared the two time points, we obtained the differential expression profiling of exosomal microRNAs. Based on bioinformatics analyses and qRT-PCR results, we provided nine up-regulated microRNAs which might be critical mediators to communicate with target cells after transfusing.What's the impact? This study expands our knowledge of exosomal microRNA expression profiling from apheresis platelet concentrates along different storage periods. This might be relevant to immunomodulation in post transfusion situations.

Development of the Chinese Haemovigilance Network and reporting of adverse transfusion reactions from 2018 to 2020.

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.

The accumulation of exosome-associated microRNA-1246 and microRNA-150-3p in human red blood cell suspensions.

BACKGROUND: Transfusion-related immunomodulation (TRIM) can be caused by exosomes, in which case, microRNAs (miRNAs) are one critical factor impacting exosome behavior. This study aims to investigate and analyze the expression profiles of exosomal miRNA in red blood cell (RBC) suspensions during storage and to identify potential TRIM-related miRNAs as well as their potential functions. METHODS: A total of 25 packs of RBC suspensions were randomly collected. Exosome were extracted by ultracentrifugation and then identified and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and western blot (WB). Exosomal miRNA profiles were acquired using gene chips in five packs on week 1 and week 5. The expression data were compared from the two time points identifying accumulated miRNAs with statistical significance and their predicted targeting genes were analyzed. Based on the gene chip results, quantitative reverse transcription-polymerase chain reactions (qRT-PCR) were performed to verify miRNA accumulation in the rest 20 packs sampling on week 1, 3 and 5. RESULTS: Gene chip analysis revealed that most exosomal miRNAs were enriched as the storage period progressed. Compared to samples from week 1, week 5 samples exhibited a total of 539 differential miRNA expressions, among which, 159 were statistically significant (P < 0.05) and 148 (93.08%) were accumulated. In the bioinformatics functional analysis, significant immunoregulatory annotations related to the thyroid hormone, mitogen-activated protein kinase (MAPK), focal adhesion and RAS signaling pathways were identified. The top 17 differential expression miRNAs were validated by qRT-PCR. The results confirmed that all the 17 miRNAs were accumulated with increasing storage time. In particular, miRNA-1246 and miRNA-150-3p were the most enriched strands by more than 150-folds in the 5-week storage period. CONCLUSIONS: As storage progressed, numerous exosomal miRNAs accumulated in the RBC suspensions, which are informatically connected to multiple immuno-signaling pathways. MiRNA-1246 and miRNA-150-3p may be essential mediators impacting the immunoregulation functions of exosomes in RBC suspensions, considering their significant accumulating scales. Further research should therefore focus on the relationship between these miRNAs and TRIM.

Donor tolerability of convalescent plasma donation.

BACKGROUND: Since early 2020, convalescent plasma has been widely used for treating coronavirus disease 2019 (COVID-19). There is limited information regarding donor tolerability of convalescent plasma donation. In this study, we evaluated the short-term donor tolerability of convalescent plasma donation. METHODS: A prospective study of 309 convalescent plasma donation related adverse events were conducted at Wuhan Blood Center of China, from February 12 to April 1, 2020. Additionally, up to 28-day post-donation follow-ups were performed on the donors. RESULTS: Sixteen (5.2%) adverse events were reported in 309 donations. All of these were mild vasovagal without loss of consciousness. The frequency of adverse reactions was higher in donors with a per donation volume of >8 mL/kg body weight or ≥ 600 mL, <100 mm Hg in pre-donation systolic blood pressure, or less than 28 days from the onset of COVID-19 symptoms. There was no correlation to donation history, weight, sex, ABO blood type, pre-donation diastolic blood pressure, pulse, or hemoglobin. CONCLUSION: The donation of convalescent plasma is generally safe. Mitigation of risk factors associated with adverse events can further enhance donor tolerability of convalescent plasma donation.

First annual report of Chinese haemovigilance network.

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.

Integration of quantitative proteomics and metabolomics reveals tissue hypoxia mechanisms in an ischemic-hypoxic rat model.

Tissues hypoxia caused by hemorrhage is a common complication in many clinical diseases. However, its pathological mechanism remains largely unknown. To partly address this issue, an ischemic-hypoxic rat model was established and the plasma proteomic and metabolic profiles were quantified and analyzed using TMT-based quantitative proteomics and metabolomics. The analysis revealed a total of 177 differentially expressed proteins and 32 metabolites that were uniquely altered in the hypoxic rat plasma, compared to the control. Bioinformatics analysis showed that these altered proteins and metabolites were involved in a wide range of biological processes. Twelve of the 177 differentially expressed proteins were involved in PI3K-Akt signaling, a pathway that has been reported to be strongly associated with tissue hypoxia. Other signaling pathways such as complement and coagulation cascades, GnRH signaling, relaxin signaling, protein processing in endoplasmic reticulum, as well as AGE-RAGE signaling were markedly altered in the ischemic-hypoxic response, implying their potential roles in tissue hypoxia. A joint analysis of proteome and metabolome showed that the significantly altered metabolites such as guanine, tryptamine, dopamine, hexadecenoic, l-methionine, and fumarate may have participated in the pathogenesis of tissue hypoxia. Further, we found that changes in the levels of metabolites matched the changes in protein abundance within the same pathway. Overall, this study presents an overview of the molecular networks in ischemic-hypoxic pathology and offers biochemical basis for further study on the mechanism of tissue hypoxia. SIGNIFICANCE: We employed an integrated metabonomic-proteomic method to systematically analyze the profiles of metabolites and proteins in an ischemic-hypoxic rat model. Bioinformatics and enrichment analysis showed that the differentially expressed proteins were mainly involved in complement and coagulation cascades, PI3K-Akt signaling, GnRH signaling, relaxin signaling, protein processing in endoplasmic reticulum, and AGE-RAGE signaling. Moreover, a panel of 12 candidate proteins involved in PI3K-Akt signaling (i.e., Vtn, Hsp90b1, Ywhae, Tnc, Ywhaz, Thbs4, Lamc1, Col1a1, Il2rg, Egfr, Newgene 621,351, and Tfrc) may serve as the potential biomarkers to predict tissue hypoxia.

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial.

Importance: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed. Objective: To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19. Design, Setting, and Participants: Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled. Intervention: Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity. Main Outcomes and Measures: Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours. Results: Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, -10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care. Conclusion and Relevance: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000029757.

Successful treatment of a centenarian with coronavirus disease 2019 (COVID-19) using convalescent plasma.

BACKGROUND: Because treatment options for coronavirus disease 2019 (COVID-19) are very limited, the use of convalescent plasma has bee explored. CASE PRESENTATION AND TREATMENT: A male centenarian with cough and dyspnea for 2 months was diagnosed with COVID-19. Without effective treatments and with the increased risks of antiviral therapy for the elderly, this patient was given convalescent plasma. The viral load, complete blood count, inflammatory indicators, vital signs, and clinical symptoms were observed before and after COVID-19 convalescent plasma transfusion. RESULTS: After convalescent plasma transfusion, significant improvement was observed on laboratory indicators and clinical symptoms of the patient. Concurrently, SARS-CoV-2 viral load decreased sharply after the first transfusion (from 2.55 × 104 to 1.39 × 103 copies/mL) and became undetectable after the second transfusion. CONCLUSIONS: With the substantial increase of COVID-19 in recent months,treatment for elderly patients has become restricted in some countries. The successful treatment of this 100-year-old patient using convalescent plasma suggests that we should consider adding convalescent plasma in th management of the elderly.

Appropriateness of red blood cell use in China in the last thirteen years: A systematic review.

OBJECTIVE: To determine both the rates of appropriate red blood cells (RBCs) use in China and where inappropriate use is particularly prevalent. BACKGROUND: In China, obtaining the comprehensive picture in unnecessary RBCs transfusion is helpful for understanding the strained blood supplies and targeting training of clinicians. STUDY DESIGN: and methods: Eligible studies were mainly retrieved from four Chinese medical databases and four databases from abroad. In all studies, the appropriateness of RBCs transfusion in transfusion cases, blood request forms, or RBC units within the last thirteen years was determined by using national guidelines. Relationships between RBCs-transfusion appropriateness and type of RBCs-transfusion record, geographical region, level of hospital (LOH-2 and LOH-3), department type (operative vs. non-operative), and study quality (high vs. low) were analyzed by Chi-squared tests. RESULTS: On average, 72.30% (standard deviation, SD = 18.87%) of all cases/forms/units throughout China were appropriate. The appropriateness of RBCs-transfusion differed significantly depending on RBCs-transfusion record type, they were 69.10%, 68.85%, and 75.64% for blood request forms, transfusion cases, and RBCs units, respectively (p < 0.001). The southwest and northeast were the most (80.62%) and the least (66.57%) appropriate transfusion areas, respectively. The coefficients of variances (CV) for the geographical regions differed significantly (0.029-0.39). LOH-3 were more appropriate than LOH-2 (p < 0.001). Non-operative departments were more appropriate than operative departments (p < 0.001). High-quality studies reported higher appropriate rate than low-quality studies (74.48% vs. 69.72%, p < 0.001). CONCLUSION: In China, unnecessary RBCs transfusion was common and may exacerbate the current pressure on blood supplies. Clinicians in certain geographical regions, LOH-2, and operative departments should be targeted with training in transfusion medicine.

Preventing murine transfusion-related acute lung injury by expansion of CD4+ CD25+ FoxP3+ Tregs using IL-2/anti-IL-2 complexes.

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.

HNA-3a and HNA-3b antigens among 9 ethnic populations and the Han population in Southwest China.

BACKGROUND: Human neutrophil antigen 3 (HNA-3) is encoded by the SLC44A2 gene. Antibodies against HNAs can cause severe, often fatal, transfusion reactions, known as transfusion-related acute lung injury, and neonatal neutropenia. We explored the 2 common HNA-3 variants in 9 ethnic populations residing in Sichuan and Yunnan provinces of China as compared to the Han population. METHODS: We genotyped for SLC44A2 (rs2288904) by polymerase chain reaction sequence-based typing among blood donors, for a total of 2206 individuals in Yunnan and 376 in Sichuan. RESULTS: The SLC44A2*02 allele (HNA-3b antigen) frequency varied between 0.24 and 0.33 for all 9 ethnic populations in Yunnan, including Zhuang, Derung, Hani, Lisu, Bai, Miao, Dai, Naxi, and Yi. Specifically, the Yi ethnicity did not present an unusually great SLC44A2*02 frequency at any of the 4 locations examined in Yunnan. Except of the Yi ethnicity in Sichuan (0.40), the Han ethnicity, as the majority population group, had the greatest SLC44A2*02 frequency with 0.39 in Yunnan and 0.35 in Sichuan. CONCLUSION: The ethnic populations in Southwest China are not at an increased risk for anti-HNA3a compared to the Han population, with the possible exception of Yi in Sichuan. Our data, however, corroborated the known high prevalence of SLC44A2*02 in Han populations. Hence, the Han populations in Yunnan, Sichuan and elsewhere in China are at a comparatively great risk for developing HNA-3a antibodies.

Complement Split Products C3a/C5a and Receptors: Are They Regulated by Circulating Angiotensin II Type 1 Receptor Autoantibody in Severe Preeclampsia?

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.