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Infectious diseases have influenced population genetics and the evolution of the structure of the human genome in part by selecting for host susceptibility alleles that modify pathogenesis. Norovirus infection is associated with ∼90% of epidemic non-bacterial acute gastroenteritis worldwide. Here, we show that resistance to Norwalk virus infection is multifactorial. Using a human challenge model, we showed that 29% of our study population was homozygous recessive for the α(1,2)fucosyltransferase gene ( FUT2 ) in the ABH histo-blood group family and did not express the H type-1 oligosaccharide ligand required for Norwalk virus binding. The FUT2 susceptibility allele was fully penetrant against Norwalk virus infection as none of these individuals developed an infection after challenge, regardless of dose. Of the susceptible population that encoded a functional FUT2 gene, a portion was resistant to infection, suggesting that a memory immune response or some other unidentified factor also affords protection from Norwalk virus infection.

Background Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. Methods Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m 2 at day −14 and day −1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. Results Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. Conclusion Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

Objective This study aimed to create a group of nursing intervention (cluster nursing) strategies of phototherapy for neonates and to evaluate clinical effects of intervention measures on reducing neonatal jaundice in neonates. Methods We performed a prospective study. A total of 141 patients with neonatal ABO hemolytic jaundice were included and randomly divided into two groups: intervention group and control group. The intervention group adopted cluster nursing measures in combination with continuous phototherapy (blue light), while the control group adopted routine nursing together with continuous phototherapy (blue light). Results No differences were observed in general characteristics between the groups. On the seventh day of treatment, percutaneous bilirubin levels were significantly lower in the intervention group than in the control group. On the seventh day of treatment, milk intake was significantly higher and the duration of hospitalization was significantly shorter in the intervention group than in the control group. Conclusion Use of cluster nursing measures in combination with phototherapy in neonatal ABO hemolysis can effectively reduce bilirubin levels, improve symptoms of jaundice, and shorten the course of the disease.

Background The failure in standard triple therapy has recently increased to high levels in China, primarily because of insufficient patient compliance, antimicrobial resistance, and high costs. Effective prevention and eradication of Helicobacter pylori ( H. pylori ) by artificial passive immunization with orally administered bovine antibodies in the milk has been demonstrated in many animal studies, but the clinical studies that are available have shown no H. pylori eradication. This study was to evaluate the efficacy and safety of orally administered bovine anti- H. pylori antibodies for the clearance of H. pylori infecting O blood group subpopulations. Methods Two local epidemic H. pylori strains that were prevalent locally were screened and then used to immunize dairy cows. After confirmation of the presence of anti- H. pylori polyclonal antibodies in the milk by enzyme-linked immunosorbent assay, the milk was subsequently defatted and processed into sterile milk by pasteurization. This study was designed as a double-blind placebo-controlled randomized clinical trial. Our 61 H. pylori -infected O blood group subjects were assigned to two groups; 31 subjects were treated with bovine milk containing antibodies and 30 subjects with the placebo. The medication-based study was continued for 28 days. Subjects were followed up for 56 days. The effect was assessed by the C-14 urea breath test (UBT). SPSS 17.0 software for Windows was used to analyze the data. Results Of the 61 subjects enrolled, 58 completed the protocol. One volunteer in the antibodies group and two volunteers in the control group dropped out. Of the 30 antibody-treated subjects, 13 became UBT negative, whereas none of the 30 of the placebo-treated subjects became UBT negative after the medication. Of 13 UBT negative patients, 3 became positive again at the end of the follow-up. Both intention to treat and per-protocol analysis indicated a significant difference in the clearance rate of infected patients between the groups treated with bovine antibody-containing milk and the placebo (P = 0.001, P < 0.05) and no significant difference in adverse effects (P > 0.05 all). Conclusions Bovine antibody-based oral immunotherapy appears to be safe and has a significant clearance effect on intragastric H. pylori that infects O blood group adults. Trial registration: ChiCTR-TRC-14005212.

This crystallographic study shows the attachment of human rotavirus VP8* to histo blood group A antigen, and suggests how changes within the structure of VP8* could allow switching from sialylated to non-sialylated glycan receptor. Rotavirus surface protein targets blood-group antigen Rotaviruses are the major pathogens of infantile gastroenteritis. They attach to the surfaces of cells through interactions with specific cellular glycans. Animal rotaviruses bind to glycans with terminal sialic acid, whereas human rotavirus strains are sialidase insensitive. Venkataram Prasad and colleagues now show that certain human rotavirus strains bind to and infect cells through A-type histo-blood group antigen (HBGA), suggesting that susceptibility to specific human rotavirus strains might be influenced by different blood-group antigens, a phenomenon reported in Helicobacter pylori and norovirus infection. Crystallographic studies show how HBGA binds to the attachment protein of human norovirus (VP8), and suggest how subtle changes in the structure of VP8 might allow receptor switching. As with many other viruses, the initial cell attachment of rotaviruses, which are the major causative agent of infantile gastroenteritis, is mediated by interactions with specific cellular glycans 1 , 2 , 3 , 4 . The distally located VP8* domain of the rotavirus spike protein VP4 (ref. 5 ) mediates such interactions. The existing paradigm is that ‘sialidase-sensitive’ animal rotavirus strains bind to glycans with terminal sialic acid (Sia), whereas ‘sialidase-insensitive’ human rotavirus strains bind to glycans with internal Sia such as GM1 (ref. 3 ). Although the involvement of Sia in the animal strains is firmly supported by crystallographic studies 1 , 3 , 6 , 7 , it is not yet known how VP8* of human rotaviruses interacts with Sia and whether their cell attachment necessarily involves sialoglycans. Here we show that VP8* of a human rotavirus strain specifically recognizes A-type histo-blood group antigen (HBGA) using a glycan array screen comprised of 511 glycans, and that virus infectivity in HT-29 cells is abrogated by anti-A-type antibodies as well as significantly enhanced in Chinese hamster ovary cells genetically modified to express the A-type HBGA, providing a novel paradigm for initial cell attachment of human rotavirus. HBGAs are genetically determined glycoconjugates present in mucosal secretions, epithelia and on red blood cells 8 , and are recognized as susceptibility and cell attachment factors for gastric pathogens like Helicobacter pylori 9 and noroviruses 10 . Our crystallographic studies show that the A-type HBGA binds to the human rotavirus VP8* at the same location as the Sia in the VP8* of animal rotavirus, and suggest how subtle changes within the same structural framework allow for such receptor switching. These results raise the possibility that host susceptibility to specific human rotavirus strains and pathogenesis are influenced by genetically controlled expression of different HBGAs among the world’s population.

Matching ABO blood group antigens between donors and recipients is critical to prevent hyperacute rejection in kidney transplantation. Enzymatic conversion of blood group antigens to the universal O type presents a promising strategy to overcome barriers in ABO-incompatible kidney transplantation. In this study, we employ α-galactosidase from Bacteroides fragilis to convert type B kidneys to type O during hypothermic machine perfusion. After 3 hours of perfusion with enzyme, more than 95% of blood group B antigens in the kidney endothelium are effectively removed. Subsequently, enzyme-treated kidneys are protected from antibody-mediated injuries in an ex vivo simulation of ABO-incompatible kidney transplantation. Encouraged by these results, a discarded type B kidney, following enzymatic conversion, is transplanted into a type O brain-dead recipient with high titer of anti-B antibody. The allograft survives for 63 hours without hyperacute rejection. Blood group B antigens re-express within 48 hours, with histopathological analyses indicating no evidence of antibody-mediated rejection. This enzymatic conversion approach holds the potential to broaden the practice of ABO-incompatible kidney transplantation, decrease waiting times and facilitate equitable organ allocation. The complexity of matching ABO blood groups presents a formidable barrier to successful transplantation. Here, the authors show that an enzymatic converted type B kidney was transplanted into a type O brain-dead recipient without hyperacute rejection.

Pure red-cell aplasia developed in a type O–positive recipient of a type A–positive allogeneic stem-cell transplant. The condition was refractory to darbepoetin alfa, glucocorticoids, and rituximab but responded promptly to daratumumab, an anti-CD38 antibody.

IgE antibodies to gal-α-1,3-gal-β-1,4-GlcNAc (α-gal) can mediate a novel form of delayed anaphylaxis to red meat. Although IgG antibodies to α-gal (anti-α-gal or anti-Gal) are widely expressed in humans, IgE anti-α-gal is not. We explored the relationship between the IgG and IgE responses to both α-gal and the related blood group B antigen. Contradicting previous reports, antibodies to α-gal were found to be significantly less abundant in individuals with blood group B or AB. Importantly, we established a connection between IgE and IgG responses to α-gal: elevated titers of IgG anti-α-gal were found in IgE-positive subjects. In particular, proportionally more IgG1 anti-α-gal was found in IgE-positive subjects against a background of IgG2 production specific for α-gal. Thus, two types of immune response to α-gal epitopes can be distinguished: a 'typical' IgG2 response, presumably in response to gut bacteria, and an 'atypical', Th2-like response leading to IgG1 and IgE in addition to IgG2. These results suggest that IgE to a carbohydrate antigen can be formed (probably as part of a glycoprotein or glycolipid) even against a background of bacterial immune stimulation with essentially the same antigen.

ABO-incompatible kidney transplantation (ABO-i KT) facilitates transplantation across blood types; however, antibody-mediated rejection (ABMR) remains a major concern, particularly in blood type O recipients. This retrospective study evaluated the effect of immunoglobulin G (IgG) monitoring and machine learning (ML)-based IgG prediction on post-transplant outcomes in 408 ABO-i KT recipients treated between 2014 and 2020. In blood type O recipients, the introduction of IgG monitoring (Era 2) was associated with a significantly lower incidence of ABMR ( P  = 0.041) and acute rejection ( P  = 0.037) compared with Immunoglobulin M (IgM)-only monitoring (Era 1). A higher initial IgM titer was identified as a risk factor for ABMR. To address the absence of IgG data in the IgM-only cohort, an ML model was developed using 610 cases to predict pre-transplant IgG titers based on IgM levels, number of plasmapheresis sessions, and ABO blood type. The model demonstrated good predictive performance (mean absolute error [MAE] = 0.593, R 2  = 0.721) and indicated that 12.2% of type O recipients in the IgM-only era were estimated to have high IgG titers (≥ 1:64). These findings support the clinical utility of IgG monitoring and ML-based estimation to enhance immunologic risk stratification and optimize preconditioning strategies in ABO-i KT.

Background The histo-blood group ABO system has been associated with adverse outcomes in COVID-19, thromboembolic diseases and Plasmodium falciparum malaria. An integral part of the severe malaria pathogenesis is rosetting, the adherence of parasite infected red blood cells (RBCs) to uninfected RBCs. Rosetting is influenced by the host’s ABO blood group (Bg) and rosettes formed in BgA have previously been shown to be more resilient to disruption by heparin and shield the parasite derived surface antigens from antibodies. However, data on rosetting in weak BgA subgroups is scarce and based on investigations of relatively few donors. Methods An improved high-throughput flow cytometric assay was employed to investigate rosetting characteristics in an extensive panel of RBC donor samples of all four major ABO Bgs, as well as low BgA expressing samples. Results All non-O Bgs shield the parasite surface antigens from strain-specific antibodies towards P. falciparum erythrocyte membrane protein 1 (PfEMP1). A positive correlation between A-antigen levels on RBCs and rosette tightness was observed, protecting the rosettes from heparin- and antibody-mediated disruption. Conclusions These results provide new insights into how the ABO Bg system affects the disease outcome and cautions against interpreting the results from the heterogeneous BgA phenotype as a single group in epidemiological and experimental studies. Graphical Abstract