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Pediatrics Jun 2024Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in ∼4% of...
BACKGROUND AND OBJECTIVES
Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in ∼4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors.
METHODS
We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes.
RESULTS
A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion.
CONCLUSIONS
Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia.
Topics: Humans; Female; Pregnancy; Infant, Newborn; Isoantibodies; Rh Isoimmunization; Erythroblastosis, Fetal; Pregnancy Outcome; Rh-Hr Blood-Group System; Male; Rho(D) Immune Globulin; Adult; Retrospective Studies
PubMed: 38784990
DOI: 10.1542/peds.2023-064604 -
Ethiopian Journal of Health Sciences Sep 2023Red blood cell antigens are numerous in structural and functional diversity; some are proteins while others are carbohydrates. The international society of blood...
BACKGROUND
Red blood cell antigens are numerous in structural and functional diversity; some are proteins while others are carbohydrates. The international society of blood transfusion currently recognized 43 blood group systems containing 349 red cell antigens. It also acknowledged 9 blood group systems (ABO, Rhesus, Kell, Duffy, Kidd, MNS, P, Lewis, and Lutheran) that are clinically significant and associated with hemolytic transfusion reactions as well as hemolytic disease of fetuses and newborns. The objective of this study was to assess the distribution of minor blood group antigens and their phenotype among voluntary blood donors in Ethiopian blood and tissue bank service in Addis Ababa.
METHOD
A cross-sectional study was conducted from January to March 2022 among 260 volunteer blood donors to determine minor blood group antigens and their phenotype at EBTBS, Addis Ababa, Ethiopia. Tests were performed using Galileo Neo Immucor, which is fully automated Immunohematology analyzer.
RESULT
A total of 260 blood donors were screened of which 153 (59%) were males. The antigen frequencies of minor blood group systems were: Fy(a), Fy(b), Jk(a), Jk(b), k, S, s were 33.5%, 43.5%, 97.7%), 40.4%), 100%, 45%, 90%, respectively. Regarding phenotype distribution, the most common phenotypes were: Duffy Fy (a-b+) 36.9%, MNS S-s+ 55% and Kidd Jk (a+b-) 59.6%.
CONCLUSION
This study highlights the frequencies of Fy(a), Fy(b), Jk(a), Jk(b), k, S and s blood group antigens and their phenotypes in volunteer blood donors at EBTBS, Addis Ababa. For the management of alloimmunization cases in transfused patients, knowledge of these minor blood group antigens is relevant.
Topics: Humans; Ethiopia; Blood Donors; Blood Group Antigens; Male; Female; Cross-Sectional Studies; Phenotype; Adult; Young Adult; Middle Aged; Blood Banks; Adolescent; Blood Grouping and Crossmatching
PubMed: 38784499
DOI: 10.4314/ejhs.v33i5.11 -
Obstetrics and Gynecology Jul 2024To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial.
METHODS
A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated.
RESULTS
A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations.
CONCLUSION
Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov , NCT02299414.
Topics: Humans; Female; Pregnancy; Infant, Newborn; Adult; Antihypertensive Agents; Hypertension; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Arterial Pressure; Hypertension, Pregnancy-Induced
PubMed: 38781591
DOI: 10.1097/AOG.0000000000005611 -
Vox Sanguinis May 2024To evaluate the severity of haemolytic disease of the foetus and newborn (HDFN) in subsequent pregnancies with RhD immunization and to identify predictive factors for...
BACKGROUND AND OBJECTIVES
To evaluate the severity of haemolytic disease of the foetus and newborn (HDFN) in subsequent pregnancies with RhD immunization and to identify predictive factors for severe disease.
MATERIALS AND METHODS
Nationwide prospective cohort study, including all pregnant women with RhD antibodies. All women with at least two pregnancies with RhD antibodies and RhD-positive foetuses were selected. The main outcome measure was the severity of HDFN in the first and subsequent pregnancy at risk. A subgroup analysis was performed for the group of women where RhD antibodies developed after giving birth to an RhD-positive child and thus after receiving anti-D at least twice (group A) or during the first pregnancy at risk for immunization (group B).
RESULTS
Sixty-two RhD immunized women with a total of 150 RhD-positive children were included. The severity of HDFN increased for the whole group significantly in the subsequent pregnancy (p < 0.001), although it remained equal or even decreased in 44% of women. When antibodies were already detected at first trimester screening in the first immunized pregnancy, after giving birth to an RhD-positive child (group A), severe HDFN in the next pregnancy was uncommon (22%). Especially when no therapy or only non-intensive phototherapy was indicated during the first immunized pregnancy (6%) or if the antibody-dependent cell-mediated cytotoxicity result remained <10%. Contrarily, women with a negative first trimester screening and RhD antibodies detected later during the first pregnancy of an RhD-positive child (group B), often before they had ever received anti-D prophylaxis, were most prone for severe disease in a subsequent pregnancy (48%).
CONCLUSION
RhD-mediated HDFN in a subsequent pregnancy is generally more severe than in the first pregnancy at risk and can be estimated using moment of antibody detection and severity in the first immunized pregnancy. Women developing antibodies in their first pregnancy of an RhD-positive child are at highest risk of severe disease in the next pregnancy.
PubMed: 38772910
DOI: 10.1111/vox.13651 -
Cancer Research Communications Jun 2024Acute GVHD (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) associated with gut microbiota disruptions. However, whether... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Acute GVHD (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) associated with gut microbiota disruptions. However, whether therapeutic microbiota modulation prevents aGVHD is unknown. We conducted a randomized, placebo-controlled trial of third-party fecal microbiota transplantation (FMT) administered at the peak of microbiota injury in 100 patients with acute myeloid leukemia receiving induction chemotherapy and alloHCT recipients. Despite improvements in microbiome diversity, expansion of commensals, and shrinkage of potential pathogens, aGVHD occurred more frequently after FMT than placebo. Although this unexpected finding could be explained by clinical differences between the two arms, we asked whether a microbiota explanation might be also present. To this end, we performed multi-omics analysis of preintervention and postintervention gut microbiome and serum metabolome. We found that postintervention expansion of Faecalibacterium, a commensal genus with gut-protective and anti-inflammatory properties under homeostatic conditions, predicted a higher risk for aGVHD. Faecalibacterium expansion occurred predominantly after FMT and was due to engraftment of unique donor taxa, suggesting that donor Faecalibacterium-derived antigens might have stimulated allogeneic immune cells. Faecalibacterium and ursodeoxycholic acid (an anti-inflammatory secondary bile acid) were negatively correlated, offering an alternative mechanistic explanation. In conclusion, we demonstrate context dependence of microbiota effects where a normally beneficial bacteria may become detrimental in disease. While FMT is a broad, community-level intervention, it may need precision engineering in ecologically complex settings where multiple perturbations (e.g., antibiotics, intestinal damage, alloimmunity) are concurrently in effect.
SIGNIFICANCE
Post-FMT expansion of Faecalibacterium, associated with donor microbiota engraftment, predicted a higher risk for aGVHD in alloHCT recipients. Although Faecalibacterium is a commensal genus with gut-protective and anti-inflammatory properties under homeostatic conditions, our findings suggest that it may become pathogenic in the setting of FMT after alloHCT. Our results support a future trial with precision engineering of the FMT product used as GVHD prophylaxis after alloHCT.
Topics: Humans; Graft vs Host Disease; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Male; Female; Middle Aged; Hematopoietic Stem Cell Transplantation; Adult; Leukemia, Myeloid, Acute; Transplantation, Homologous; Faecalibacterium; Aged; Acute Disease; Feces; Metabolome; Multiomics
PubMed: 38767452
DOI: 10.1158/2767-9764.CRC-24-0138 -
Revista Brasileira de Ginecologia E... 2024RhD alloimmunization in pregnancy is still the main cause of hemolytic disease of the fetus and neonate (HDFN). Nevertheless, there are other antigens that may be... (Review)
Review
RhD alloimmunization in pregnancy is still the main cause of hemolytic disease of the fetus and neonate (HDFN). Nevertheless, there are other antigens that may be associated with the occurrence of this phenomenon and that have been growing in proportion, given that current prevention strategies focus only on anti-RhD antibodies. Although not widespread, the screening and diagnostic management of the disease caused by these antibodies has recommendations in the literature. For this reason, the following review was carried out with the objective of listing the main red blood cell antigen groups described - such as Rh, ABO, Kell, MNS, Duffy, Kidd, among others - addressing the clinical importance of each one, prevalence in different countries, and recommended management when detecting such antibodies during pregnancy.
PubMed: 38765509
DOI: 10.61622/rbgo/2024AO22 -
FASEB Journal : Official Publication of... May 2024Mesenchymal stromal cells (MSCs) have been shown to modulate the function of various subsets of T cells such as naïve CD4 T cells and IFNγCD4 Th1 cells; however,...
Mesenchymal stromal cells (MSCs) have been shown to modulate the function of various subsets of T cells such as naïve CD4 T cells and IFNγCD4 Th1 cells; however, mechanisms underlying this regulation have not been fully deciphered. Our in vitro culture assays demonstrate that MSCs suppress the activation and function of CD4 T cells by secreting interleukin 11, and neutralization of IL11 abrogates MSC-mediated suppression of CD4 T cell function. Moreover, delayed-type, exogenous supplementation of IL11 significantly suppressed IFNγ expression by Th1 cells. Th1 and CD8 cells play central roles in T cell-mediated tissue damage. Using a murine model of hypersensitivity response to study T cell-mediated tissue damage, we show that silencing IL11 in MSCs significantly abates the capacity of MSCs to suppress the generation of IFNγ-secreting CD4 and CD8 cells, failing to prevent T cell-mediated tissue inflammation and tissue damage.
Topics: Animals; Mesenchymal Stem Cells; Th1 Cells; Mice; Interleukin-11; Mice, Inbred C57BL; CD8-Positive T-Lymphocytes; Interferon-gamma; CD4-Positive T-Lymphocytes; Cells, Cultured; Female
PubMed: 38758184
DOI: 10.1096/fj.202400078R -
Blood May 2024Hemolytic disease of the fetus and newborn (HDFN) remains an important cause of perinatal morbidity and mortality. HDFN is caused by maternal alloimmunization to red...
Hemolytic disease of the fetus and newborn (HDFN) remains an important cause of perinatal morbidity and mortality. HDFN is caused by maternal alloimmunization to red blood cell (RBC) antigens. This article describes and highlights issues in the care of pregnant women with red blood cell (RBC) alloimmunization. This includes monitoring for, and management of fetal anemia caused by maternal red cell alloantibodies, but also considerations for transfusion support for the woman in the event of major bleeding. Many aspects of care for women with RBC alloantibodies are not covered within specific guidelines, particularly with respect to best practice for antenatal management of women with prior significant obstetric morbidity or mortality due to HDFN, and we will outline our approach in these cases. The use of non-invasive monitoring for fetal anemia through measurement of the middle cerebral artery peak systolic velocity has led to a paradigm shift in antenatal care for women with high-risk antibodies, and medical therapies hold promise for women with the most severe disease.
PubMed: 38743880
DOI: 10.1182/blood.2023022894 -
Immunohematology Apr 2024This extraordinary case showcases the identification of a rare anti-En specificity that was assisted by DNA-based red blood cell antigen typing and collaboration between...
This extraordinary case showcases the identification of a rare anti-En specificity that was assisted by DNA-based red blood cell antigen typing and collaboration between the hospital blood bank in the United States, the home blood center in Qatar, the blood center Immunohematology Reference Laboratory, as well as the American Rare Donor Program (ARDP) and the International Society for Blood Transfusion (ISBT) International Rare Donor Panel. En is a high-prevalence antigen, and blood samples from over 200 individuals of the extended family in Qatar were crossmatched against the patient's plasma with one compatible En(a-) individual identified. The ISBT International Rare Donor Panel identified an additional donor in Canada, resulting in a total of two En(a-) individuals available to donate blood for the patient.
Topics: Humans; Blood Group Antigens; Blood Donors; Blood Transfusion; Blood Grouping and Crossmatching; Qatar; Male; Female; Blood Group Incompatibility
PubMed: 38739026
DOI: 10.2478/immunohematology-2024-003 -
Food and Chemical Toxicology : An... Jul 2024Published studies on the glycosylation, absorption, distribution, metabolism, excretion, and safety outcomes of orally ingested recombinant human lactoferrin (rhLF) were... (Review)
Review
Published studies on the glycosylation, absorption, distribution, metabolism, excretion, and safety outcomes of orally ingested recombinant human lactoferrin (rhLF) were reviewed in the context of unanswered safety questions, including alloimmunization, allergenicity, and immunotoxicity potential of rhLF during repeated exposure. The primary objective was to summarize current safety data of rhLF produced in transgenic host expression systems. Overall, results from animal and human studies showed that rhLF was well tolerated and safe. Animal data showed no significant toxicity-related outcomes among any safety or tolerability endpoints. The no observed adverse effect levels (NOAEL) were at the highest level tested in both iron-desaturated and -saturated forms of rhLF. Although one study reported outcomes of rhLF on immune parameters, no animal studies directly assessed immunogenicity or immunotoxicity from a safety perspective. Data from human studies were primarily reported as adverse events (AE). They showed no or fewer rhLF-related AE compared to control and no evidence of toxicity, dose-limiting toxicities, or changes in iron status in various subpopulations. However, no human studies evaluated the immunomodulatory potential of rhLF as a measure of safety. Following this review, a roadmap outlining preclinical and clinical studies with relevant safety endpoints was developed to address the unanswered safety questions.
Topics: Lactoferrin; Humans; Animals; Recombinant Proteins; Food Safety; No-Observed-Adverse-Effect Level
PubMed: 38735359
DOI: 10.1016/j.fct.2024.114727