The Distribution Patterns of Rhesus (Rh) Antigens.

INTRODUCTION: The determination of one's blood group is dictated by the inheritance-based diversity in the presence or absence of RBC antigens on the surface. Extended Rhesus (Rh) antigens are the most clinically relevant antigens of blood group systems after the ABO blood group system in transfusion medicine. The aim of this study was to serologically assess the prevalence of extended Rh antigens across diverse blood group systems. METHODS: A total of 2043 samples were tested for the ABO blood group and Rh typing with monoclonal antisera. The Rh phenotyping (C, c, E, e ) was performed on all the samples. RESULTS: The most frequently observed ABO blood group was O (36.5%), while AB (13.6%) was identified as the least prevalent. Positive Rh D antigen was found in 91.6% of tested samples, while 8.4% were Rh D-negative. The most frequently encountered antigen was e, followed by D, while the least prevalent was E. DISCUSSION: Establishing a Rh phenotype repository for blood donors and conducting Rh phenotype assessments as part of pretransfusion testing before initiating the initial blood transfusion for each patient could significantly lower the patients' incidence of alloimmunization.

Diversity and selection analyses identify transmission-blocking antigens as the optimal vaccine candidates in Plasmodium falciparum.

BACKGROUND: A highly effective vaccine for malaria remains an elusive target, at least in part due to the under-appreciated natural parasite variation. This study aimed to investigate genetic and structural variation, and immune selection of leading malaria vaccine candidates across the Plasmodium falciparum's life cycle. METHODS: We analysed 325 P. falciparum whole genome sequences from Zambia, in addition to 791 genomes from five other African countries available in the MalariaGEN Pf3k Database. Ten vaccine antigens spanning three life-history stages were examined for genetic and structural variations, using population genetics measures, haplotype network analysis, and 3D structure selection analysis. FINDINGS: Among the ten antigens analysed, only three in the transmission-blocking vaccine category display P. falciparum 3D7 as the dominant haplotype. The antigens AMA1, CSP, MSP119 and CelTOS, are much more diverse than the other antigens, and their epitope regions are under moderate to strong balancing selection. In contrast, Rh5, a blood stage antigen, displays low diversity yet slightly stronger immune selection in the merozoite-blocking epitope region. Except for CelTOS, the transmission-blocking antigens Pfs25, Pfs48/45, Pfs230, Pfs47, and Pfs28 exhibit minimal diversity and no immune selection in epitopes that induce strain-transcending antibodies, suggesting potential effectiveness of 3D7-based vaccines in blocking transmission. INTERPRETATION: These findings offer valuable insights into the selection of optimal vaccine candidates against P. falciparum. Based on our results, we recommend prioritising conserved merozoite antigens and transmission-blocking antigens. Combining these antigens in multi-stage approaches may be particularly promising for malaria vaccine development initiatives. FUNDING: Purdue Department of Biological Sciences; Puskas Memorial Fellowship; National Institute of Allergy and Infectious Diseases (U19AI089680).

Different roles of the heterodimer architecture of galectin-4 in selective recognition of oligosaccharides and lipopolysaccharides having ABH antigens.

The dimeric architecture of tandem-repeat type galectins, such as galectin-4 (Gal-4), modulates their biological activities, although the underlying molecular mechanisms have remained elusive. Emerging evidence show that tandem-repeat galectins play an important role in innate immunity by recognizing carbohydrate antigens present on the surface of certain pathogens, which very often mimic the structures of the human self-glycan antigens. Herein, we have analyzed the binding preferences of the C-domain of Gal-4 (Gal-4C) towards the ABH-carbohydrate histo-blood antigens with different core presentations and their recognition features have been rationalized by employing a combined experimental approach including NMR, solid-phase and hemagglutination assays and molecular modeling. The data show that Gal-4C prefers A- over B-antigens (twofold in affinity), contrary to the N-domain (Gal-4N), although both domains share the same preference for the type-6 presentations. The behavior of the full-length tandem-repeat form (Gal-4FL) has been additionally scrutinized. ITC and NMR data demonstrate that both domains within Gal-4FL bind to the histo-blood antigens independently of each other, with no communication between them. In this context, the heterodimeric architecture does not play any major role, apart from the complementary A and B-antigen binding preferences. However, upon binding to a bacterial lipopolysaccharide (LPS) containing a multivalent version of an H-antigen mimetic as O-antigen, the significance of the galectin architecture was revealed. Indeed, our data point to the linker peptide domain and the F-face of the C-domain as key elements that provide Gal-4 with the ability to cross link multivalent ligands, beyond the glycan binding capacity of the dimer.

Evaluation of chimeric recombinant antigens for the serodiagnosis of Trypanosoma cruzi in dogs: a promising tool for Chagas disease surveillance.

BACKGROUND: Chagas disease (CD), a neglected parasitic disease caused by Trypanosoma cruzi, poses a significant health threat in Latin America and has emerged globally because of human migration. Trypanosoma cruzi infects humans and over 100 other mammalian species, including dogs, which are important sentinels for assessing the risk of human infection. Nonetheless, the serodiagnosis of T. cruzi in dogs is still impaired by the absence of commercial tests. In this study, we investigated the diagnostic accuracy of four chimeric recombinant T. cruzi IBMP antigens (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) for detecting anti-T. cruzi antibodies in dogs, using latent class analysis (LCA). METHODS: We examined 663 canine serum samples, employing indirect ELISA with the chimeric antigens. LCA was utilized to establish a latent variable as a gold standard for T. cruzi infection, revealing distinct response patterns for each antigen. RESULTS: The IBMP (Portuguese acronym for the Molecular Biology Institute of Paraná) antigens achieved area under the ROC curve (AUC) values ranging from 90.9% to 97.3%. The highest sensitivity was attributed to IBMP-8.2 (89.8%), while IBMP-8.1, IBMP-8.3, and IBMP-8.4 achieved 73.5%, 79.6%, and 85.7%, respectively. The highest specificity was observed for IBMP-8.4 (98.6%), followed by IBMP-8.2, IBMP-8.3, and IBMP-8.1 with specificities of 98.3%, 94.4%, and 92.7%, respectively. Predictive values varied according to prevalence, indicating higher effectiveness in endemic settings. CONCLUSIONS: Our findings underscore the remarkable diagnostic performance of IBMP-8.2 and IBMP-8.4 for the serodiagnosis of Trypanosoma cruzi in dogs, representing a promising tool for the diagnosis of CD in dogs. These chimeric recombinant antigens may not only enhance CD surveillance strategies but also hold broader implications for public health, contributing to the global fight against this neglected tropical disease.

Potential Involvement of Human Leukocyte Antigen-DR/DQ Polymorphisms with Schizophrenia Among Patients with Schizophrenia in Yemen.

Objectives: To evaluate the hypothesis that human leukocyte antigens (HLAs) confer susceptibility to schizophrenic disorders, by assessing their contribution to the risk of schizophrenia in a Yemeni population. Methods: The researchers approached patients who had been diagnosed with schizophrenia at Al-Amal Hospital for Psychiatric Diseases, Sana'a. Controls were drawn randomly from the general population. The HLA class II alleles of the participants were examined. The genotypes of the HLA-DQB1 and HLA-DRB1 alleles were determined by polymerase chain reaction using sequence-specific primers. Results: The subjects comprised 110 patients with schizophrenia, matched by an equal number of controls. The prevalence of HLA-DRB1*04 was significantly higher among patients than among controls (7.3% vs. 0.0%; p =0.003), as was HLA-DRB1*07 (62.7% vs. 17.3%, odds ratio (OR) = 8.1, 95% CI: 4.3-15.1; p < 0.001). HLA-DRBI*14 was significantly less prevalent among patients (0.9% vs. 11.8%, OR = 0.06, 95% CI: 0.01-0.50, χ2 = 10.9; p < 0.001). HLA-DQB1*07 was the most common allele discovered in schizophrenia patients and was found to have a much higher incidence in patients than the control group (22.7% vs. 4.5%, OR = 6.2, 95%CI: 2.3-16.8, χ2 = 15.4; p < 0.001). Conclusions: The HLA-DQB1 and HLA-DRB1 gene loci are linked to schizophrenia in the Yemeni population, according to the current study's evidence.

Production and evaluation of a new set of recombinant antigens for the serological diagnosis of Human cysticercosis.

Human cysticercosis caused by Taenia soliun (T. soliun) is endemic in certain areas of Latin America, Asia and Sub-Saharan Africa. Neurocysticercosis (NCC) is mainly diagnosed by neuroimaging, which, in most cases, is unavailable in endemic areas. Due to their high sensitivity and specificity, serological tests such as enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) based on the glycosylated fraction of the cyst CS50 are widely used for the detection of the anti-cysticercus IgG antibodies despite their significant cost and the need of cysticercus material. Given their cost-effectivess and simplicity, immunoassays based on recombinant proteins could provide new alternatives for human cysticercosis diagnosis: such tests would be aimed at screening those people living in remote areas who need further examination. To date, however, no test using recombinant antigens is commercially available. Herein, five recombinant proteins (R14, R18, R93.1, R914.1, and R915.2) were produced, three of which (R93.1, R914.1, and R915.2) were newly identified from the cyst fluid. Evaluation of the diagnostic performance of these recombinant antigens by ELISA was done using sera from 200 epileptic and non-epileptic individuals in comparison with the WB-CS50 as the reference serological method. Recombinant proteins-based ELISA showed a level of diagnostic performance that is inferior than the reference serological method, but similar to that of the native antigen ELISA for human cysticercosis (commonly used for screening). Further optimization of expression conditions is still needed in order to improve proteins solubility and enhance diagnostic performance for human cysticercosis detection. However, this preliminary evaluation of the recombinant antigens has shown their potential valuable use for screening cysticercosis in patients with epilepsy attending dispensaries in remote areas. Future studies should be conducted to evaluate our recombinant antigens in a large group of patients with different stages of NCC, and in correlation with imaging findings.

Exploring Galectin Interactions with Human Milk Oligosaccharides and Blood Group Antigens Identifies BGA6 as a Functional Galectin-4 Ligand.

Galectins (Gals), a family of multifunctional glycan-binding proteins, have been traditionally defined as ß-galactoside binding lectins. However, certain members of this family have shown selective affinity towards specific glycan structures including human milk oligosaccharides (HMOs) and blood group antigens. In this work, we explored the affinity of human galectins (particularly Gal-1, -3, -4, -7 and -12) towards a panel of oligosaccharides including HMOs and blood group antigens using a complementary approach based on both experimental and computational techniques. While prototype Gal-1 and Gal-7 exhibited differential affinity for type I vs. type II Lac/LacNAc residues and recognized fucosylated neutral glycans, chimera-type Gal-3 showed high binding affinity towards poly-LacNAc structures including LNnH and LNnO. Notably, the tandem-repeat human Gal-12 showed preferential recognition of 3-fucosylated glycans, a unique feature among members of the galectin family. Finally, Gal-4 presented a distinctive glycan-binding activity characterized by preferential recognition of specific blood group antigens, also validated by saturation transfer difference nuclear magnetic resonance (STD-NMR) experiments. Particularly, we identified oligosaccharide blood group A type 6 (BGA6) as a biologically relevant Gal-4 ligand, which specifically inhibited IL-6 secretion induced by this lectin on human peripheral blood mononuclear cells. These findings highlight unique determinants underlying specific recognition of HMOs and blood group antigens by human galectins, emphasizing the biological relevance of Gal-4-BGA6 interactions, with critical implications in the development and regulation of inflammatory responses.

Advanced applications of Nanodiscs-based platforms for antibodies discovery.

Due to their fundamental biological importance, membrane proteins (MPs) are attractive targets for drug discovery, with cell surface receptors, transporters, ion channels, and membrane-bound enzymes being of particular interest. However, due to numerous challenges, these proteins present underutilized opportunities for discovering biotherapeutics. Antibodies hold the promise of exquisite specificity and adaptability, making them the ideal candidates for targeting complex membrane proteins. They can target specific conformations of a particular membrane protein and can be engineered into various formats. Generating specific and effective antibodies targeting these proteins is no easy task due to several factors. The antigen's design, antibody-generation strategies, lead optimization technologies, and antibody modalities can be modified to tackle these challenges. The rational employment of cutting-edge lipid nanoparticle systems for retrieving the membrane antigen has been successfully implemented to simplify the mechanism-based therapeutic antibody discovery approach. Despite the highlighted MP production challenges, this review unequivocally underscores the advantages of targeting complex membrane proteins with antibodies and designing membrane protein antigens. Selected examples of lipid nanoparticle success have been illustrated, emphasizing the potential of therapeutic antibody discovery in this regard. With further research and development, we can overcome these challenges and unlock the full potential of therapeutic antibodies directed to target complex MPs.

Rh Blood Group Antigens and Alloimmunization Risk of Pregnant Women in South Western, Nigeria.

BACKGROUND: Rh blood group antigens are the second most important blood group antigens in clinical transfusion due to their immunogenicity and prevalence. Childbirth, miscarriage, and other obstetrics events are risk factors for alloimmunization in women which increases the likelihood of haemolytic blood transfusion reaction and hemolytic disease of the fetal/newborn (HDNF/B). Even though there are several data on the RhD status of our populations. However, there is a dearth of data on pregnant women's C, E, c, and e status, their alloimmunization risk, and rates in Nigeria. OBJECTIVES: This study aims to provide information on the distribution of the Rh major antigens and risk factors for alloimmunization in pregnant women in southwestern Nigeria. MATERIALS AND METHODS: This was a descriptive cross-sectional study of 133 pregnant women attending routine ante-natal clinics. Questionnaires were administered to collect biodata and obstetrics history. ABO blood grouping and Rh phenotyping were carried out on their blood samples using RAPID LABS Monoclonal Rhesus Typing Reagent. RESULTS AND DISCUSSION: Rh blood group antigen c was present in 100% of the women, followed by e (98.5%) and D (95.5%). C and E are the least prevalent antigens and probably the ones to which antibodies may be formed. The commonest Rh phenotype was Dce. Of all the pregnant women, alloimmunization was present in 0.8%. Of those who were RhD negative, alloimmunization was present in 16.7%. Pregnant women are more likely to be alloimmunized against C and E antigens than c and e antigens due to their low and high frequencies respectively.

CONTEXTE: Les antigènes du groupe sanguin Rh sont les seconds plus importants en transfusion clinique en raison de leur immunogénicité et de leur prévalence. L'accouchement, la fausse couche et d'autres événements obstétriques sont des facteurs de risque d'alloimmunisation chez les femmes, augmentant ainsi la probabilité de réactions hémolytiques lors de transfusions sanguines et de maladies hémolytiques du fœtus/nouveau-né (HDNF/B). Bien qu'il existe plusieurs données sur le statut RhD de nos populations, il y a un manque de données sur le statut des antigènes C, E, c et e chez les femmes enceintes, leur risque d'alloimmunisation et les taux associés au Nigéria. OBJECTIFS: Cette étude vise à fournir des informations sur la distribution des principaux antigènes Rh et les facteurs de risque d'alloimmunisation chez les femmes enceintes dans le sud-ouest du Nigéria. MÉTHODOLOGIE: Il s'agit d'une étude descriptive transversale de 133 femmes enceintes fréquentant les cliniques prénatales de routine. Des questionnaires ont été administrés pour collecter des données biodémographiques et des antécédents obstétriques. La détermination des groupes sanguins ABO et le phénotypage Rh ont été réalisés sur leurs échantillons de sang à l'aide du réactif de typage Rh monoclonal RAPID LABS. RÉSULTATS ET DISCUSSION: L'antigène c du groupe sanguin Rh était présent chez 100 % des femmes, suivi de e (98,5 %) et D (95,5 %). Les antigènes C et E sont les moins prévalents et probablement ceux contre lesquels des anticorps peuvent être formés. Le phénotype Rh le plus courant était Dce. Parmi toutes les femmes enceintes, l'alloimmunisation était présente chez 0,8 %. Parmi celles qui étaient RhD négatives, 'alloimmunisation était présente chez 16,7 %. Les femmes enceintes sont plus susceptibles de développer une alloimmunisation contre les antigènes C et E que contre les antigènes c et e en raison de leurs fréquences respectives faibles et élevées. MOTS-CLÉS: Antigènes du groupe sanguin Rh, Phénotype, Alloanticorps érythrocytaires, Femmes enceintes.

Sugar and arginine facilitate oral tolerance by ensuring the functionality of tolerogenic immune cell subsets in the intestine.

Although oral tolerance is a critical system in regulating allergic disorders, the mechanisms by which dietary factors regulate the induction and maintenance of oral tolerance remain unclear. To address this, we explored the differentiation and function of various immune cells in the intestinal immune system under fasting and ad libitum-fed conditions before oral ovalbumin (OVA) administration. Fasting mitigated OVA-specific Treg expansion, which is essential for oral tolerance induction. This abnormality mainly resulted from functional defects in the CX3CR1+ cells responsible for the uptake of luminal OVA and reduction of tolerogenic CD103+ dendritic cells. Eventually, fasting impaired the preventive effect of oral OVA administration on asthma and allergic rhinitis development. Specific food ingredients, namely carbohydrates and arginine, were indispensable for oral tolerance induction by activating glycolysis and mTOR signaling. Overall, prior food intake and nutritional signals are critical for maintaining immune homeostasis by inducing tolerance to ingested food antigens.

An Analytical Protocol for Detecting Antibody Titer Levels in Serum/Saliva by Indirect Enzyme-Linked Immunosorbent Assay (ELISA).

Enzyme-linked immunosorbent assay (ELISA) detects qualitatively and quantitatively the presence of antibodies or antigens in a sample. Due to its simplicity, high sensitivity, and user-friendliness, the test is widely used in laboratory research, clinical diagnoses, and food testing. This chapter describes the indirect semiquantitative ELISA protocol used to monitor antibody levels in animals and analyze the titer levels of specific antibodies against a target antigen in serum and saliva.

Current status and future directions for the development of human papillomavirus vaccines.

The development of human papillomavirus (HPV) vaccines has made substantive progress, as represented by the approval of five prophylactic vaccines since 2006. Generally, the deployment of prophylactic HPV vaccines is effective in preventing newly acquired infections and incidences of HPV-related malignancies. However, there is still a long way to go regarding the prevention of all HPV infections and the eradication of established HPV infections, as well as the subsequent progression to cancer. Optimizing prophylactic HPV vaccines by incorporating L1 proteins from more HPV subtypes, exploring adjuvants that reinforce cellular immune responses to eradicate HPV-infected cells, and developing therapeutic HPV vaccines used either alone or in combination with other cancer therapeutic modalities might bring about a new era getting closer to the vision to get rid of HPV infection and related diseases. Herein, we summarize strategies for the development of HPV vaccines, both prophylactic and therapeutic, with an emphasis on the selection of antigens and adjuvants, as well as implications for vaccine efficacy based on preclinical studies and clinical trials. Additionally, we outline current cutting-edge insights on formulation strategies, dosing schedules, and age expansion among HPV vaccine recipients, which might play important roles in addressing barriers to vaccine uptake, such as vaccine hesitancy and vaccine availability.

Merkel cell polyomavirus pan-T antigen knockdown reduces cancer cell stemness and promotes neural differentiation independent of RB1.

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer associated with integration of Merkel cell polyomavirus (MCPyV). MCPyV-encoded T-antigens (TAs) are pivotal for sustaining MCC's oncogenic phenotype, i.e., repression of TAs results in reactivation of the RB pathway and subsequent cell cycle arrest. However, the MCC cell line LoKe, characterized by a homozygous loss of the RB1 gene, exhibits uninterrupted cell cycle progression after shRNA-mediated TA repression. This unique feature allows an in-depth analysis of the effects of TAs beyond inhibition of the RB pathway, revealing the decrease in expression of stem cell-related genes upon panTA-knockdown. Analysis of gene regulatory networks identified members of the E2F family (E2F1, E2F8, TFDP1) as key transcriptional regulators that maintain stem cell properties in TA-expressing MCC cells. Furthermore, minichromosome maintenance (MCM) genes, which encodes DNA-binding licensing proteins essential for stem cell maintenance, were suppressed upon panTA-knockdown. The decline in stemness occurred simultaneously with neural differentiation, marked by the increased expression of neurogenesis-related genes such as neurexins, BTG2, and MYT1L. This upregulation can be attributed to heightened activity of PBX1 and BPTF, crucial regulators of neurogenesis pathways. The observations in LoKe were confirmed in an additional MCPyV-positive MCC cell line in which RB1 was silenced before panTA-knockdown. Moreover, spatially resolved transcriptomics demonstrated reduced TA expression in situ in a part of a MCC tumor characterized by neural differentiation. In summary, TAs are critical for maintaining stemness of MCC cells and suppressing neural differentiation, irrespective of their impact on the RB-signaling pathway.

Excessive use of preoperative blood type and antibody screening: A retrospective observational study conducted in a hospital in Norway.

INTRODUCTION: This study aimed to identify the blood transfusion rates for several surgical procedures in a single district general hospital and assess the value of preoperative blood type and antibody screen across all relevant surgical procedures. We hypothesized that there was an overuse of blood type and antibody screen in our general surgical population. METHODS: A database containing transfusions of patients who underwent elective- or emergency surgery from January 2015 to September 2020 was matched to a database of preoperative type-and-screen performed in the same period. Registered procedures where the incidence of transfusion is deemed low were excluded. The included procedures were assessed for the intraoperative usefulness of type- and-screen testing. RESULTS: In the included 68.892 surgeries, 36.134 (52.0%) blood samples were preoperatively tested for the blood type and screened for antibodies according to the hospital's routine. Overall 3.517 (5.1%) of surgeries had patients that received a transfusion in the perioperative period and 1.2% (n = 850) during the surgery. CONCLUSION: Most surgeries had a very low incidence of transfusion. Despite this, type-and-screen tests were widely used. This suggests the need for a more focused pre-surgery type-and-screen approach, and a more data driven approach to local guidelines in collaboration with surgical specialties.

Long-term storage stability of PGL-I coated ELISA plates for anti-Mycobacterium leprae IgM detection.

The assessment of ELISA plates coated with phenolic glycolipid-I/PGL-I revealed excellent stability during eight years of storage at room temperature, promoting consistent IgM antibody detection in multibacillary leprosy patients. These stable, standardized plates can significantly contribute to efficient leprosy serology research and support its widespread distribution and use in endemic countries.

Seroepidemiology of hepatitis B virus (HBV) and relationship to serum transaminase levels in Indian population.

Background: Hepatitis B virus (HBV) infection is a serious public health issue that must be addressed. Aim: The goal of this study was to investigate the correlation between serological status for hepatitis Be antigen (HBeAg)/anti-HBe, serum transaminase levels, and serum HBV-DNA in patients with chronic HBV infection. Methods: A retrospective observational study with 620 patients with persistent HBV infection (mean age, 36.35 years; 506 men) was conducted. All patients tested positive for hepatitis B surface antigen (HBsAg). Liver profile, HBeAg, and anti-HBe antibody tests were conducted for all patients. Additionally, serum HBV DNA was examined using a DNA assay in these individuals. Results: Of 620 patients, 114 (18.39%) were HBeAg-positive and 506 (81.61%) HBeAg-negative. A detectable level of HBV DNA was found in 89.79% of HBeAg-positive/anti-HBe negative patients compared to HBeAg-negative/anti-HBe positive carriers 33.69% (P value <0.0001). The median viral load was significantly higher in HBeAg-positive cases (4.72 log10 copies/mL) than in HBeAg-negative individuals (4.23 log10 copies/mL; P = 0.997). Additionally, a higher proportion of HBeAg-positive samples (P = 0.0001) had HBV-DNA levels above 10,000 copies/mL.

Transfer of celiac disease-associated immunogenic gluten peptides in breast milk: variability in kinetics of secretion.

Background: Exposure to antigens is crucial for child immune system development, aiding disease prevention and promoting infant health. Some common food antigen proteins are found in human breast milk. However, it is unclear whether gluten antigens linked to celiac disease (CD) are transmitted through breast milk, potentially impacting the development of the infant's immune system. Objective: This study aimed to analyze the passage of gluten immunogenic peptides (GIP) into human breast milk. We evaluated the dynamics of GIP secretion after lactating mothers adopted a controlled gluten-rich diet. Methods: We prospectively enrolled 96 non-CD and 23 CD lactating mothers, assessing total proteins and casein in breast milk, and GIP levels in breast milk and urine. Subsequently, a longitudinal study was conducted in a subgroup of 12 non-CD lactating mothers who adopted a controlled gluten-rich diet. GIP levels in breast milk and urine samples were assayed by multiple sample collections over 96 hours. Results: Analysis of a single sample revealed that 24% of non-CD lactating mothers on a regular unrestricted diet tested positive for GIP in breast milk, and 90% tested positive in urine, with significantly lower concentrations in breast milk. Nevertheless, on a controlled gluten-rich diet and the collection of multiple samples, GIP were detected in 75% and 100% of non-CD participants in breast milk and urine, respectively. The transfer dynamics in breast milk samples were long-enduring and GIP secretion persisted from 0 to 72 h. In contrast, GIP secretion in urine samples was limited to the first 24 h, with inter-individual variations. In the cohort of CD mothers, 82.6% and 87% tested negative for GIP in breast milk and urine, respectively. Conclusions: This study definitively established the presence of GIP in breast milk, with substantial inter-individual variations in secretion dynamics. Our findings provide insights into distinct GIP kinetics observed in sequentially collected breast milk and urine samples, suggesting differential gluten metabolism patterns depending on the organ or system involved. Future research is essential to understand whether GIP functions as sensitizing or tolerogenic agents in the immune system of breastfed infants.

Safety of 300IR house dust mite sublingual tablet from pooled clinical trial and post-marketing data.

Background: The 300IR house dust mite (HDM) sublingual immunotherapy (SLIT) tablet is approved for treatment of HDM-induced allergic rhinitis (AR). To provide a comprehensive review of the 300IR HDM-SLIT tablet safety profile based on randomized controlled trial (RCT) pooled data and post-marketing (PM) pharmacovigilance data. Methods: Subjects (5-65 years) with confirmed HDM-AR with or without controlled asthma were treated with 300IR or placebo in 8 RCTs. Reported treatment-emergent adverse events (TEAEs) were pooled and analyzed descriptively in subsets of adults/adolescents and children. Adverse reactions (ADRs) collected from spontaneous reporting and PM studies through a pharmacovigilance system since the first marketing authorization were also analyzed. Results: Across RCTs, 1853 subjects were treated with the 300IR HDM-SLIT tablet and 1846 with placebo. In both subsets of adults/adolescents and children whichever their asthma status, treatment-related TEAEs of higher incidence in active groups vs placebo were mostly consistent with mild or moderate local application-site reactions. They were mainly reported on the first days of treatment and decreased over time. 4 severe laryngopharyngeal reactions (2 requiring adrenaline/epinephrine) and 1 moderate eczema considered serious rapidly resolved with medications; no anaphylaxis was reported. In PM settings, ADRs reported in more than 235,000 patients were in line with RCT findings. Severe systemic reactions occurred rarely; 12 anaphylactic reactions resolved safely (5 with adrenaline). No new safety signal was raised. Conclusion: Safety data from RCTs and more than 7 years of real-life experience confirmed the favorable safety profile of 300IR HDM-SLIT tablet in patients across different regions, regardless of age and asthma status. Clinical trial registrations: NCT00674700; Retrospectively registered 06 May 2008.NCT01199133; Retrospectively registered 09 September 2010.NCT01527188; Retrospectively registered 01 February 2012.NCT02443805; Registered 29 April 2015/EudraCT 2014-004223-46; Registered 16 September 2015.jRCT2080221872/JapicCTI-121917; Registered 01 August 2012.jRCT2080222929/JapicCTI-15298; Registered 04 August 2015.

Osteoimmunological Principles Adapted to Achieve Mechanically Superior Posterolateral Fusion in a New Zealand White Rabbit Model Using Antigen-Coated, Electrospun Beta-Tricalcium Phosphate.

Introduction Triggering the immune system via antigenic stimulation at the time of spinal fusion surgery may enhance bone morphogenesis and result in successful bony arthrodesis. We sought to demonstrate that bone morphogenesis could be enhanced via antigenic immunologic stimulation of a surgical fusion site. Methods New Zealand white rabbits underwent non-instrumented posterolateral fusion of L5-6 with implantation of either an immunologically activated graft (inert beta-tricalcium phosphate) or harvested autograft. Fusion was evaluated using plain radiographs, micro-computed tomography (CT), mechanical palpation, and biomechanical testing. The final evaluation was carried out at 12 weeks postoperatively. Results Eight rabbits received immunologically activated grafts; 10 received autografts and served as historical controls. Fusion rates were identical between groups (both 50%). Radiographs and micro CT of the fusion mass showed no significant difference between groups, and both showed good incorporation of the transverse processes into the fusion masses with radiographic evidence confirming trabeculation and bone remodeling. However, mechanical testing of the fusion sites showed superior fusion strength in the rabbits that received immunologically activated grafts, approaching a factor of two on flexion/extension, lateral bending, and axial rotation. Little to no graft material was appreciable in the non-fused antigen-treated specimens. Conclusions There is a long-standing need for a graft material that can replace autograft bone, due to the negative clinical consequences and financial costs pertaining to autologous bone harvesting. No allograft bone substitute to date has been able to reliably replicate the success of harvested autograft bone. This study suggests that immunological enhancement of inert beta-tricalcium phosphate can potentially be a substitute for allograft bone that can meet and even exceed the success of harvested autograft bone.