[Establishment of a genotyping method for the junior blood group and identification of a rare blood type with partial DVI.3 and Jr(a-)].

OBJECTIVE: To develop a genotyping method for the Junior blood type and report on a rare blood type with Jr(a-). METHODS: Healthy O-type RhD+ volunteer donors of the Shenzhen Blood Center from January to May 2021 (n = 1 568) and a pedigree with difficult cross-matching (n = 3) were selected as the study subjects. Serological methods were used for proband's blood type identification, unexpected antibody identification, and antibody titer determination. Polymerase chain reaction-sequence specific primer (PCR-SSP) method was used for typing the proband's RhD gene. ABCG2 gene coding region sequencing and a PCR-SSP genotyping method were established for determining the genotypes of the proband and his family members and screening of Jra antigen-negative rare blood type among the 1 568 blood donors. RESULTS: The proband's ABO and RhD blood types were respectively determined as B and partial D (RHDDVI.3/RHD01N.01), Junior blood type Jra antigen was negative, and plasma had contained anti-D and anti-Jra. Sequencing of the ABCG2 gene revealed that the proband's genotype was ABGG201N.01/ABGG201N.01 [homozygous c.376C>T (p.Gln126X) variants], which is the most common Jr(a-) blood type allele in the Asian population. Screening of the voluntary blood donors has detected no Jr(a-) rare blood type. Statistical analysis of the heterozygotes suggested that the allelic frequency for ABCG2*01N.01 (c.376T) was 0.45%, and the frequency of Jr(a-) rare blood type with this molecular background was about 0.2‰. CONCLUSION: A very rare case of partial DVI.3 type and Jr(a-) rare blood type has been identified. And a method for identifying the Junior blood type through sequencing the coding regions of the ABCG2 gene and PCR-SSP has been established.

Postbiotics as potential new therapeutic agents for sepsis.

Sepsis is the main cause of death in critically ill patients and gut microbiota dysbiosis plays a crucial role in sepsis. On the one hand, sepsis leads to the destruction of gut microbiota and induces and aggravates terminal organ dysfunction. On the other hand, the activation of pathogenic gut flora and the reduction in beneficial microbial products increase the susceptibility of the host to sepsis. Although probiotics or fecal microbiota transplantation preserve gut barrier function on multiple levels, their efficacy in sepsis with intestinal microbiota disruptions remains uncertain. Postbiotics consist of inactivated microbial cells or cell components. They possess antimicrobial, immunomodulatory, antioxidant and antiproliferative activities. Microbiota-targeted therapy strategies, such as postbiotics, may reduce the incidence of sepsis and improve the prognosis of patients with sepsis by regulating gut microbial metabolites, improving intestinal barrier integrity and changing the composition of the gut microbiota. They offer a variety of mechanisms and might even be superior to more conventional 'biotics' such as probiotics and prebiotics. In this review, we present an overview of the concept of postbiotics and summarize what is currently known about postbiotics and their prospective utility in sepsis therapy. Overall, postbiotics show promise as a viable adjunctive therapy option for sepsis.

MeCIPK10 regulates the transition of the K+ transport activity of MeAKT2 between low- and high-affinity molds in cassava.

AKT1 is an inward-rectifying K+ channel that was originally thought to function only within a low-affinity K+ concentration range. However, the growth of an akt1 mutant of Arabidopsis was shown to be severely inhibited within a high-affinity range. This suggested that AKT1 may also be a high-affinity K+ transporter, but it remains unclear how the two modes of AKT1 coordinate to uptake K+. One gene (MeAKT2) encodes for a putatively inward-rectifying K+ channel and was isolated from cassava. Relative to other tissues, the MeAKT2 gene was expressed mainly in roots, and its transcriptional level was observed to be significantly increased under low-K+ conditions. Functional analyses were performed using a yeast expression system. When MeAKT2 was expressed alone in yeast cells, transgenic yeast could grow only in nutrient media supplied with >0.5 mM potassium. A yeast two-hybrid assay showed that both MeCIPK10 and MeCIPK12 clearly interacted with MeAKT2. Additionally, 0.05 mM K+ was sufficient for the growth of yeast cells co-expressing MeAKT2 with MeCIPK10, but also their co-expression significantly enhanced the growth capacity of yeast cells in the low range of K+ concentrations. Change in K+ uptake rate in co-transgenic yeast cells grown across a wide range of K+ concentrations showed that MeAKT2-mediated K+ uptake displayed a biphasic pattern, but also the switching from low-to high-affinity K+ uptake was regulated by CIPK10. This indicated that MeAKT2 functioned as a dual-affinity transporter to uptake K+ under both low- and high-affinity K+ conditions.

circFTO upregulates transforming growth factor-alpha through sponging miR-148a-3p to regulate high glucose-induced ARPE-19 cells injury.

Diabetic retinopathy (DR) is one of the most common retinal microvascular diseases in diabetic patients. Therefore, elucidating the underlying molecular mechanism of DR is of great significance for its clinical treatment. This study explores the effects of the upregulated circFTO in DR patients in terms of cell apoptosis and viability. Several molecular assays are employed to explore these molecular mechanistic aspects, such as luciferase reporter, RNA pull-down, RT-qPCR, Western blot, and ELISA assays. miR-148a-3p is downregulated in DR patients. The expression of circFTO promoted ARPE-19 cells apoptosis and inhibited proliferation, reflecting the regulatory effect of circFTO/miR-148a-3p on retinal epithelial cells injury. In addition, the absence of circFTO could reduce ARPE-19 cells injury caused by HG by inhibiting oxidative stress and inflammation. Further, the investigations at the molecular level showed that circFTO could regulate the level of miR-148a-3p and TGFA in vitro. As the molecular sponge of miR-148a-3p, circFTO regulated cell viability and apoptosis and promoted the progression of DR through regulating the expression of TGFA. Together, this study provides new targets and markers for early diagnosis and therapy of DR.

The Calcium Sensor Calcineurin B-Like Proteins -Calcineurin B-Like Interacting Protein Kinases Is Involved in Leaf Development and Stress Responses Related to Latex Flow in Hevea brasiliensis.

Latex flow in Hevea brasiliensis (the Para rubber tree), the sole commercial source of natural rubber (cis-1,4-polyisoprene, NR), renders it uniquely suited for the study of plant stress responses. Calcineurin B-like interacting protein kinases (CIPK) serving as calcium-sensor protein kinases react with calcineurin B-like proteins (CBL) to play crucial roles in hormone signaling transduction and response to abiotic stress in plant developmental processes. However, little is known about their functions in Hevea. In this study, a total of twelve CBL (HbCBL) and thirty CIPK (HbCIPK) genes were identified from the Hevea genome. Structure and phylogenetic analysis assigned these CIPKs to five groups and CBLs to four groups, and mapped onto fourteen of the eighteen Hevea chromosomes. RNA-seq and qPCR analysis showed that the expressions of HbCBL and HbCIPK genes varied in the seven Hevea tissues examined, i.e., latex (cytoplasm of rubber-producing laticifers), bark, leaf, root, seed, female flower, and male flower. The expressions of two HbCBL and sixteen HbCIPK genes showed upward trends during leaf development. Following ethylene yield stimulation and the latex tapping treatment, both practices invoking stress, the expression levels of most latex-expressed genes were significantly altered. Yeast two-hybrid test revealed interactions for multiple combinations of HbCBLs and HbCIPKs with substantial gene expression in latex or other Hevea tissues. However, all the HbCBL-HbCIPK complexes examined did not recruit HbSOS1 or AtSOS1 to form functional salt tolerance SOS pathway in yeast cells. Taken together, the results suggested a role of the Hevea CBL-CIPK network as a point of convergence for several different signaling pathways in growth, development, and stress responses in relation to latex production.

Fecal microbiota transplantation and short-chain fatty acids reduce sepsis mortality by remodeling antibiotic-induced gut microbiota disturbances.

Objective: Sepsis is the leading cause of death in critically ill patients. The gastrointestinal tract has long been thought to play an important role in the pathophysiology of sepsis. Antibiotic therapy can reduce a patient's commensal bacterial population and raise their risk of developing subsequent illnesses, where gut microbiota dysbiosis may be a key factor. Methods: In this study, we analyzed the 16S rRNA of fecal samples from both healthy people and patients with sepsis to determine if alterations in gut bacteria are associated with sepsis. Then, we developed a mouse model of sepsis using cecal ligation and puncture (CLP) in order to examine the effects of fecal microbiota transplantation (FMT) and short-chain fatty acids (SCFAs) on survival rate, systemic inflammatory response, gut microbiota, and mucosal barrier function. Results: Sepsis patients' gut microbiota composition significantly differed from that of healthy people. At the phylum level, the amount of Proteobacteria in the intestinal flora of sepsis patients was much larger than that of the control group, whereas the number of Firmicutes was significantly lower. Mice with gut microbiota disorders (ANC group) were found to have an elevated risk of death, inflammation, and organ failure as compared to CLP mice. However, all of these could be reversed by FMT and SCFAs. FMT and SCFAs could regulate the abundance of bacteria such as Firmicutes, Proteobacteria, Escherichia Shigella, and Lactobacillus, restoring them to levels comparable to those of healthy mice. In addition, they increased the expression of the Occludin protein in the colon of mice with sepsis, downregulated the expression of the NLRP3 and GSDMD-N proteins, and reduced the release of the inflammatory factors IL-1ß and IL-18 to inhibit cell pyroptosis, ultimately playing a protective role in sepsis. Disccusion: FMT and SCFAs provide a microbe-related survival benefit in a mouse model of sepsis, suggesting that they may be a viable treatment for sepsis.

Hyporegenerative anemia in anti-M-associated hemolytic disease of the fetus.

BACKGROUND: The anti-M antibody can lead to hemolytic disease of the fetus and newborn (HDFN) and adverse fetal outcomes, especially in the Asian population. However, fetal erythropoiesis resulting from M alloimmunization needs further investigation. STUDY DESIGN AND METHODS: We analyzed erythropoiesis in eight fetuses with M alloimmunization and compared them with the fetuses affected by anti-D. They were matched as pairs according to the gestational age of diagnosis and the hematocrit before treatment. Paired t-tests or paired Wilcoxon rank-sum tests were conducted to compare the difference in the cord blood indexes. Pearson correlation analysis was used to evaluate the correlativity between hematocrit and the reticulocyte percentage in the two groups. RESULTS: The fetuses in the MN group had lower reticulocyte count and percentage than those in the RhD group (p < .05). All of the fetal reticulocyte production indexes (RPIs) in the MN group were less than 2, indicating an inadequate hemopoietic response to anemia, while the majority of the RPIs in the RhD group (85.7%) were significantly higher (p = .003), with 6 cases greater than 2.5. Hematocrit was negatively correlated with reticulocyte percentage (y = 54.7-171.7x, r2  = 0.825, p = .005) in the RhD group, while no significant correlation was found in the MN group. No difference in the number of IUT, interval, or the fetal outcome was found between the two groups. CONCLUSION: Fetal reticulocytopenia provided direct evidence of an inadequate hemopoietic response in HDFN due to anti-M, leading to hyporegenerative anemia. Once the IgG component of anti-M is detected, close monitoring should be considered.

A case of hyperhaemolysis syndrome in a pregnant Chinese woman with ß-thalassemia during perinatal transfusion.

OBJECTIVES: To report a case of hyperhaemolysis syndrome (HHS) that occurred during perinatal blood transfusion in a pregnant Chinese woman with ß-thalassemia to deepen the understanding of HHS and the risk of transfusion therapy for patients with thalassemia. BACKGROUND: Most HHS cases occur in people with sickle cell disease. So far, no cases of HHS have been reported in the Chinese population. Here, we report a pregnant Chinese women with ß-thalassemia experiencing HHS. METHODS: The patient received ABO- and RhD-matched red blood cell transfusion from six blood donors in four perinatal transfusions. Haemoglobinuria and lower haemoglobin levels compared to those before transfusion were observed after each transfusion, and the lactate dehydrogenase was consistently elevated. The blood samples were collected at different time points during the hospitalisation for direct antiglobulin test (DAT), antibody screening test and acid elution test. The antigens of six blood donors were identified, and the cross-matching tests were repeated using the blood sample of the patient with specific irregular antibodies after the last transfusion. RESULTS: The DAT of the patient was negative for anti-IgG and positive (1+) for anti-C3d, and no red blood cell antibodies were detected in the eluent before, between and after transfusions. Before and between transfusions, blood samples were negative for red blood cell irregular antibodies, whereas IgM anti-P1 and IgG anti-Jka were detected in blood samples the next day after the last transfusion. In the six donors, two were negative for P1 and Jka , one was positive for P1 and negative for Jka , and three were negative for P1 and positive for Jka . The tentative cross-matching tests using the indirect antiglobulin method in saline showed that only agglutination occurred in the blood samples of the patient collected after last transfusion and the three Jka -positive blood donors. DISCUSSION: The clinical manifestations and laboratory test results suggested that HHS occurred in this patient with ß-thalassemia after each transfusion. Clinicians should be aware that HHS can occur with compatible blood transfusion.

[Correlation between special A/O genotype and the O phenotype].

OBJECTIVE: To explore the correlation between special A/O genotype and the O phenotype. METHODS: Group O samples with partially reduced or lack of isoagglutinins were collected to determinate the ABO genotype with a PCR-sequence specific primer (PCR-SSP) assay. Seven samples with A/O genotype were selected for further study. Serological tests including forward and reverse typing, H antigen determination and adsorption/elution were carried out with a tube method. Genomic DNA was genotyped by amplifying and sequencing of the coding regions of exons 1 to 7 of the ABO gene. RESULTS: Seven samples were serotyped as group O by the forward typing test. However, reduced anti-A activity was found in 5 samples by the reverse typing test, reduced anti-A and anti-B activities were found in 1 sample, and no anti-A isoagglutinin activity was found with 1 sample. H antigen was determined in all samples by routine serologic method. Neither anti-A nor anti-B was eluted from red cells derived from all samples. Three samples were genotyped as Ael02/O02, whilst the remainders were Ael02/O13, Ael02/O65, Am04/O75, Ael06/O02, respectively. CONCLUSION: Special A/O genotype may not express the A antigen, leading to the generation of group O red cells. Reduced or missed anti-A activity is the typical serological feature of this special group of O phenotype, for which ABO*Ael02 and ABO*O02 are the major alleles. Group O individuals with isoagglutinin detection problem should be grouped by serological tests and genomic DNA analysis.

Hemolytic disease of the fetus and newborn due to alloanti-M: three Chinese case reports and a review of the literature.

BACKGROUND: Alloanti-M was once regarded as not clinically significant, with a few exceptions in extremely rare cases. However, an increasing number of cases of severe hemolytic disease of the fetus and newborn (HDFN), resulting in fetal hydrops and recurrent abortion caused by alloanti-M, have been reported mainly in the Asian population. STUDY DESIGN AND METHODS: Three pregnant Chinese women with a history of abnormal pregnancy with hydrops fetalis were encountered. During this pregnancy, a series of clinical examinations and an alloantibody identification against RBCs and platelets were conducted. Intrauterine transfusion and postnatal transfusion were then performed in the fetuses. In addition, the HDFN cases caused by alloanti-M reported in different ethnic groups as well as their clinical and serologic features are also summarized. RESULTS: Three pregnant women were identified with an M-N+ phenotype and IgM mixed with IgG alloanti-M in serum. Their fetuses were found by ultrasound examination and cord blood testing to have severe anemia. Additionally, an M+N+ phenotype and IgG alloanti-M were detected in the cord blood of the three fetuses with titers ranging from 1:1 to 1:128. Moreover, low reticulocyte counts and negative direct antiglobulin tests were also shown in two of the fetuses. After receiving intrauterine transfusions and postnatal transfusions several times, these three fetuses eventually survived and then healthfully developed in the follow-up tracking. CONCLUSION: Alloanti-M immunization can cause severe HDFN with hyporegenerative anemia, often seen in the Asian population, and suppression of erythropoiesis might account for it.

Transfused platelets enhance alloimmune responses to transfused KEL-expressing red blood cells in a murine model.

BACKGROUND: Factors influencing the development of alloantibodies against blood group antigens on transfused red blood cells are poorly defined. We hypothesised that transfused platelets may act as a danger signal to recipients and affect humoral immune responses to transfused red blood cells. MATERIALS AND METHODS: Platelet-rich plasma prepared from wild-type C57BL/6 or CD40L knock-out donors was transfused into wild-type or CD40L knock-out recipients. Leucoreduced red blood cells from transgenic donors expressing high levels of the human KEL glycoprotein in an erythrocyte-specific manner (KELhi donors) were transfused after the platelets, and anti-KEL responses were measured longitudinally. In some experiments, recipients were treated with poly (I:C), monoclonal CD40L-blocking antibody, or CD4-depleting antibody prior to transfusion. RESULTS: Transfusion of wild-type C57BL/6 platelets or treatment with poly (I:C) prior to KELhi red blood cell transfusion led to an anti-KEL alloimmune response in wild-type recipients. Transfusion of platelets from wild-type but not CD40L knock-out donors prior to KELhi red blood cell transfusion led to an IgG anti-KEL alloimmune response in CD40L knock-out recipients; unexpectedly, transfusion of platelets from CD40L knock-out donors prior to KELhi red blood cell transfusion led to a robust anti-KEL alloimmune response in wild-type recipients. Recipient treatment with MR1 CD40L-blocking antibody or CD4-depleting antibody prevented KEL alloimmunisation altogether. DISCUSSION: Transfused platelets serve as an adjuvant in this T-dependent murine model of anti-KEL red blood cell alloimmunisation, with CD40/CD40L interactions being involved to some degree but with additional mechanisms also playing a role. These findings raise questions about the role that transfused or endogenous platelets may play in other innate/adaptive immune responses.

Expression Patterns and Identified Protein-Protein Interactions Suggest That Cassava CBL-CIPK Signal Networks Function in Responses to Abiotic Stresses.

Cassava is an energy crop that is tolerant of multiple abiotic stresses. It has been reported that the interaction between Calcineurin B-like (CBL) protein and CBL-interacting protein kinase (CIPK) is implicated in plant development and responses to various stresses. However, little is known about their functions in cassava. Herein, 8 CBL (MeCBL) and 26 CIPK (MeCIPK) genes were isolated from cassava by genome searching and cloning of cDNA sequences of Arabidopsis CBLs and CIPKs. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed that the expression levels of MeCBL and MeCIPK genes were different in different tissues throughout the life cycle. The expression patterns of 7 CBL and 26 CIPK genes in response to NaCl, PEG, heat and cold stresses were analyzed by quantitative real-time PCR (qRT-PCR), and it was found that the expression of each was induced by multiple stimuli. Furthermore, we found that many pairs of CBLs and CIPKs could interact with each other via investigating the interactions between 8 CBL and 25 CIPK proteins using a yeast two-hybrid system. Yeast cells co-transformed with cassava MeCIPK24, MeCBL10, and Na+/H+ antiporter MeSOS1 genes exhibited higher salt tolerance compared to those with one or two genes. These results suggest that the cassava CBL-CIPK signal network might play key roles in response to abiotic stresses.

[Identification of a novel ABO B(A)07 allele].

OBJECTIVE: To explore the molecular basis for a novel B(A) phenotype. METHODS: Genomic DNA was abstracted from peripheral blood sample from the proband. ABO genotyping were carried out with sequence specific primer PCR (PCR-SSP). Exons 6 and 7 of the ABO gene were amplified with PCR and sequenced. RESULTS: Anti-A serum could not be adsorbed or eluted by the donor's red blood cells, and no irregular antibodies were found in the plasma. PCR-SSP showed that the ABO genotype of the donor was ABO *B/O. Sequencing results showed that one of the alleles was ABO *O02, while the other could not be defined but contained the following mutation points, 297A>G, 526C>G, 657C>T, 701C>T, 703G>A, 796C>A, 803G>C, and 930G>A. The data was accepted by the GenBank (the loading code was KM974887) and the Blood Group Antigen Mutation Database, and was confirmed to be a novel allele of B(A). CONCLUSION: A novel allele ABO *B(A)07 with 701C>T has been identified, which may facilitate further study on blood antigen variants and typing of the blood groups.

[Phenotype Types and Genetic Mutation Mechanism of Rhesus D Variant Individuals].

OBJECTIVE: To explore the phenotype types and genetic mutation mechanism of Rhesus D variant individuals. METHODS: Fouty-eight peripheral blood samples of pregnancies and blood donors who had been identified as Rhesus D variant by using routine serologic methods were collected from January 2013 to October 2015 in our center. The multiple ligation-dependent probe amplification(MLPA) was used to determine the RHD after genomic DNA had been extracted from the blood sample, then the data including gene copy number variations, point mutations, deletions and hybrid fusions were analyzed by GeneMarker software. All exons of blood sample RHD were amplified via PCR and analyzed by sequencing when its MLPA results were not in accordance with serologic results. Cloning and haplotype sequencing were performed if novel allele had been found. RESULTS: Rh phenotypes of the 48 samples were typed as following: 20 cases out of 48 were CcDee(41.7%, 20/48),12 cases were ccDEe (25%,12/48), 11 cases were CCDee(22.9%, 11/48), 5 cases were CcDEe (10.4%, 5/48), respectively. The MLPA analysis showed that 38 cases possessed only 1 variant allele(RHD zygosity was Dvd), while 10 cases possessed 2 variant alleles(RHD zygosity was DvDv). In Dvd type individuals, point mutations were found in 18 cases and RHD/CE hybrid fusions were found in 20 cases. In DvDv individuals, point mutations combined with RHD/CE hybrid fusions were found in 9 cases, deletion combined with RHD/CE hybrid fusions were found in 1 case. Variant alleles analysis basing on MLPA showed that 14 cases were weak D 15 and 22 cases were RhD VI type 3, however, the variant alleles were not identified in 7 cases due to lack of detecting probes and were identified via sequencing analysis. Two novel mutations, 79-81delCTC and 689G>A were also certificated by sequencing in 2 cases. CONCLUSION: CcDee is the major Rh phenotype in RhD variants, weak D 15 and RhD VI type 3 are the main serologic type of RhD variants, point mutation and RHD/CE hybrid fusions are main molecular mechanism for RhD variant phenotype. Besides, 79-81delCTC and 689G>A are two novel alleles.

Inhibition of Anaphase-Promoting Complex by Silence APC/CCdh1 to Enhance Radiosensitivity of Nasopharyngeal Carcinoma Cells.

The aim of this study was to investigate the possibility of APC/CCdh1 as a potential therapeutic target in the radiosensitivity of nasopharyngeal carcinoma (NPC) cell CNE-1, and explain the role of APC subunits after silence of Cdh1 combined with radiotherapy. Transfection with Cdh1 shRNA significantly increased the radiosensitivity of CNE-1 cells and the radiation enhancement ratio (RER) of sh-Cdh1 cells was 1.76. Knockdown of Cdh1 in CNE-1 cells increased irradiation induced apoptosis and G2/M phase cell cycle arrest. The levels of CDC20 and CylinB1 increased and the levels of Ku70 and APC3 decreased after irradiation. APC/CCdh1 is involved in regulation of radiosensitivity in human NPC CNE-1 cells. Our study may provide a promising therapeutic strategy for NPC by targeting Cdh1. J. Cell. Biochem. 118: 3150-3157, 2017. © 2016 Wiley Periodicals, Inc.

The Enhancement of Radiation Sensitivity in Nasopharyngeal Carcinoma Cells via Activation of the Rac1/NADPH Signaling Pathway.

We reported in an earlier study that using mass spectrometry and bioinformatic analysis demonstrated Rac1 protein might be mostly mitochondrial target in the radiosensitization process of nasopharyngeal carcinoma CNE-1 cells. The goal of our current study was to reveal the relationship between Rac1/NADPH pathway and radiosensitization in CNE-1 cells using Rac1 activator, phorbol 12-myristate 13-acetate (PMA) and Rac1 inhibitor NSC23766. The Rac1-GTP expression was determined using a pulldown assay, the Rac1 location using a immunofluorescence with a laser scanning confocal microscope, the NADPH oxidase activity with NBT assay and the reactive oxygen species with DCFH-DA probe. The apoptosis rate was analyzed by flow cytometry, and the expressions of p67(phox) and NFκB-p105/p50 were analyzed by Western blot. After treatment with PMA and 2 Gy radiation (compared to the control), Rac1-GTP was activated and translocated to the cell membrane. NADPH oxidase activity, reactive oxygen species of intracellular concentration and the apoptosis rate increased significantly. The expression of p67(phox) and NFκB-p50 protein also increased. However, in the cells treated with NSC23766 alone or NSC23766 combined with 2 Gy irradiation, the results were just the opposite. Overall, these results indicate that the Rac1 protein may be the key target involved in the radiosensitization of nasopharyngeal carcinoma cells. The activated Rac1/NADPH pathway combined with radiation can increase the radiosensitivity of nasopharyngeal carcinoma cells, and the Rac1/NADPH pathway may be the signaling pathway involved in the radiosensitization process.

H435-containing immunoglobulin G3 allotypes are transported efficiently across the human placenta: implications for alloantibody-mediated diseases of the newborn.

BACKGROUND: The neonatal receptor (FcRn) extends the half-life of human immunoglobulin (Ig)G and transports it across the placenta, providing the newborn with humoral immunity. Of the four subclasses, IgG3 stands out with strong effector functions, short half-life (7 days vs. 21 days for other subclasses), and poor placental transport. We recently described how a single-amino-acid polymorphism at Position 435 in IgG3 is sufficient to explain the short half-life of R435-containing IgG3 and demonstrated that H435-IgG3 has a normal half-life of 21 days. Here, we investigated whether the R435 also explains the relatively poor placental transport of IgG3. STUDY DESIGN AND METHODS: Sera were collected from paired mothers and newborns at birth. The study included six mothers expressing R435-IgG diagnosed with fetal and neonatal alloimmune thrombocytopenia and treated with intravenous immune globulin (IVIG; containing H435-IgG3, also known as G3m16 or G3m(s,t) allotype), as well as 33 paired samples of both G3m16(-) and G3m16(+) mothers. Placental IgG transport was estimated by comparing cord and maternal concentrations of IgG subclass and G3m16 allotype. RESULTS: The placental transport of naturally occurring H435-IgG3 allotypes was significantly more efficient than that of other R435-IgG3 allotypes and was comparable to IgG1 transport. CONCLUSION: We demonstrate that the poor maternal-fetal transport of IgG3 is only true for most individuals of western populations where the G3m16 is not common. In G3m16(+) individuals, expressing H435-containing IgG3, IgG3 transport is similar to IgG1, which may give rise to enhanced complications in pregnancy-associated alloimmune disease in ethnic communities where this naturally occurring H435 containing IgG3 allotype is more frequent.

The summary of FUT1 and FUT2 genotyping analysis in Chinese para-Bombay individuals including additional nine probands from Guangzhou in China.

BACKGROUND: The para-Bombay phenotype is characterized by the absence or weak expression of ABH antigens on the surface of red blood cells, but normal expression in saliva. STUDY DESIGN AND METHODS: The para-Bombay phenotype of the nine Chinese probands was identified by standard serologic techniques. The coding regions of FUT1 and FUT2 genes were amplified by polymerase chain reaction and then directly sequenced. ABO genotyping was performed by polymerase chain reaction with sequence-specific priming method. The FUT1 and FUT2 genotypes and the distribution in all reported Chinese para-Bombay individuals including our study were also summarized. RESULTS: Five FUT1 genotypes, h1h3 (n = 3), h1h2 (n = 3), h1h1 (n = 1), h3h3 (n = 1), and h2h3 (n = 1), and three functional FUT2 genotypes, Se(357) Se(357) (n = 4), Se(357) Se(357, 716) (n = 4), and Se(357) Se(357, 385) (n = 1) described before were identified in nine probands. CONCLUSIONS: The review of the literature shows that a total of 17 FUT1 alleles and four FUT2 alleles (Se(357), Se(357,716), Se(357 385), Se) have been identified in Chinese para-Bombay individuals. The four FUT1 alleles, h1 (547delAG), h2 (880delTT), h3 (C658T), and h4 (C35T; A980C) are most prevalent, which account for more than 90% of all allele counts and are essential to be involved when developing para-Bombay genotyping kit for Chinese.