Non-sensitised Women Research Articles

Prevention of Rhesus-alloimmunisation: a cost-effectiveness analysis

BackgroundRhesus disease of a newborn baby results from the entrance of anti-D antibodies of the rhesus factor D (RhD)-negative mother into the RhD positive foetal bloodstream. This transfer might cause stillbirths, neonatal deaths, or severe hyperbilirubinemia, which can develop into irreversible brain damage. In current practice, anti-D immunoglobulin is administered to RhD-negative women within 72 h after the delivery of RhD-positive newborn babies. During the antepartum period, it is given in events associated with placental trauma or disruption of the feto-maternal interface. This review was conducted to analyse the cost-effectiveness of the introduction of worldwide guidelines for the administration of anti-D immunoglobulin at 28 weeks to all RhD negative mothers with RhD-positive spouses in Palestine. MethodsThis was a cost-effective analysis and a literature review of the international guidelines about RhD alloimmunisation prophylaxis. The US, Australian, Canadian, UK, and WHO guidelines were reviewed. A cost-effective analysis was done, and the primary outcomes were the number needed to treat and the overall cost of the treatment. Estimations were done for the cost of prevention to every case. FindingsAll reviewed guidelines recommend that the administration of anti-D immunoglobulin is given routinely to all RhD-negative non-sensitised women at 28 weeks gestation, when the fetal blood type is unknown or the father is known to be RhD-positive. This practice is cost-effective, hence the implementation of the new guideline will cost approximately US$700 000 in Palestine ($400 000 in the West Bank and $300 000 in the Gaza Strip). The implementation of this guideline will prevent 148 cases (85 in the West Bank and 63 in the Gaza Strip) from further RhD alloimmunisation. The net cost of prevention of every case is approximately $4750. InterpretationRoutine administration of anti-D immunoglobulin to all RhD-negative non-sensitised women at 28 weeks gestation, when the spouses are RhD-positive, is cost-effective. An implementation programme for RhD alloimmunisation prophylaxis will be of great value. FundingNone.

Do Women Truly Have Less Than Optimal Outcome Post-Heart Transplantation Compared to Men

<h3>Purpose</h3> It has been reported from the ISHLT registry that women have less optimal outcome after heart transplantation (HTx) compared to men. It is not known whether this difference is due to rejection, NF-MACE, or decreased survival. <h3>Methods</h3> Between 2010 and 2020, we assessed 1071 HTx patients and divided them by male and female sex. 309 females and 762 males were included in the study. Post-transplant outcomes included 1-year survival, 1-year freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30% by angiography), 1-year freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), 1-year freedom from rejection (acute cellular rejection [ACR], antibody-mediated rejection [AMR]), and 1-year freedom from de novo DSA production. Women were divided into two groups, sensitized (PRA >10%) or non-sensitized. <h3>Results</h3> When comparing women to men, women had similar survival, freedom from CAV, and freedom from NF-MACE, but significantly lower freedom from ATR, AMR, and de novo DSA production. Women who were sensitized had similar survival but lower freedom from rejection and DSA production compared to non-sensitized women. 26% of our female patients were sensitized. <h3>Conclusion</h3> Major post-transplant outcomes are similar for women and men. However, sensitization may be the reason for more AMR in women but it does not affect short-term major outcomes. Longer follow-up and impact of these outcomes need to be assessed.

Longitudinal profile of circulating T follicular helper lymphocytes parallels anti-HLA sensitization in renal transplant recipients.

Antibody-mediated rejection is responsible for 30%-50% of renal graft failures. Differentiation of B cells into antibody-producing plasmablasts depends on the collaboration of follicular helper T cells (Tfh). We analyzed circulating Tfh (cTfh) in kidney recipients and studied cTfh relationship with anti-HLA antibody production and graft outcome. cTfh were longitudinally analyzed in a prospective cohort of patients (n=206), pre- and posttransplantation. Clinical data, HLA sensitization, and cTfh function were recorded. Both pretransplant and 6-month posttransplant cTfh were able to derive IgG-producing plasmablasts. Pretransplant cTfh was decreased in patients, especially in those who received dialysis. However, these cells were increased in patients with previous allograft or transfusions and in HLA-sensitized recipients. After transplantation cTfh expanded, significantly more in patients who developed de novo anti-HLA antibodies than in patients who remained unsensitized. Augmented pretransplant cTfh positively correlated with higher intensity of pretransplant anti-HLA class I and with de novo anti-HLA class I and anti-HLA class II antibodies. Consistently, pretransplantation cTfh were higher in patients who experienced acute rejection (HR=1.14 [1.04-1.25]). Thus, we show a role for Tfh in anti-HLA sensitization and rejection. Multicenter studies with additional patient cohorts are needed to validate these results. Immunosuppressive drugs targeting Tfh could be useful to improve outcomes.

Pregnancy modulates the allergen-induced cytokine production differently in allergic and non-allergic women.

The immunological environment during pregnancy may differ between allergic and non-allergic women. This study investigates the effect of maternal allergy on the allergen-induced cytokine and chemokine levels and whether pregnancy modulates these immune responses differently in allergic and non-allergic women. The birch-, cat-, phytohemagglutinin- and tetanus toxoid-induced interferon-γ (IFN-γ), interleukin (IL)-4, IL-5, IL-10, IL-13, the T-helper 1 (Th1)-associated chemokine CXCL10 and the Th2-associated chemokine CCL17 levels were quantified in 20 women with allergic symptoms (sensitized, n=13) and 36 women without allergic symptoms (non-sensitized, n=30) at gestational weeks 10-12, 15-16, 25, 35 and 2 and 12months post-partum. Birch-, but not cat-induced, IL-5, IL-13 and CCL17 levels were increased during pregnancy as compared to post-partum in the sensitized women with allergic symptoms. In contrast, cat-, but not birch-induced, IL-5 and IL-13 levels were increased during pregnancy as compared to post-partum in the non-sensitized women without allergic symptoms. Furthermore, IFN-γ secretion was increased in the first and decreased in the second and third trimesters in response to birch and decreased in the third trimester in response to cat as compared to post-partum in the non-sensitized women without allergic symptoms. Increased allergen-induced IL-4, IL-5 and IL-13 levels were associated with allergic symptoms and sensitization. Pregnancy had a clear effect on the allergen-induced IL-5, IL-13, CCL17, IFN-γ and CXCL10 production, with distinct enhanced Th2-responses to birch in the allergic group and to cat in the non-allergic group.

BCSH guideline for the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn.

BCSH guideline for the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn.

Fetal RHD genotype detection from circulating cell‐free fetal DNA in maternal plasma in non‐sensitized RhD negative women

To examine the performance of the SensiGene Fetal RHD Genotyping Laboratory Developed Test (RHD Genotyping LDT) using circulating cell-free fetal DNA (ccff DNA) extracted from maternal plasma. ccff DNA was extracted from maternal blood from non-sensitized women with singleton pregnancies in two cohorts, one with a serotype reference (11-13 weeks' gestation) and one with the reference source (6-30 weeks' gestation). The presence of three RHD exon sequences (exons 4, 5, 7), the psi-pseudogene, three Y-chromosome sequences (SRY, DBY and TTTY2), and the X/Y-chromosome TGIF gene control were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-the RHD Genotyping LDT. The cohort with a serotype RhD reference showed correct classification in 201 of 207 patients, a test accuracy of 97.1%, with a sensitivity and specificity for prediction of RhD serotype of 97.2 and 96.8%, respectively. The cohort with a genotype RHD reference showed correct classification in 198 of 199 patients, indicating a test accuracy of 99.5% with a sensitivity and specificity for prediction of RHD genotype of 100.0 and 98.3%, respectively. Fetal RHD genotyping can accurately be determined using ccff DNA in the first and second trimesters of pregnancy.

Total and allergen-specific IgE levels during and after pregnancy in relation to maternal allergy

Type 2 T-helper cell (Th2)-skewed immunity is associated with successful pregnancy and the ability to easily direct immune responses to a Th2-polarised profile may be an evolutionary benefit. The Th2-like immunity associated with allergic disease might generate favourable effects for the maintenance of pregnancy, but could also promote development of Th2-like immune responses and allergic disease in the offspring. The aim of this study was to explore, by using IgE as a stable proxy for Th2, the Th1/Th2 balance in allergic and non-allergic women by measuring allergen-specific and total IgE antibody levels in plasma during pregnancy and after delivery. Specific and total IgE antibody levels were determined by ImmunoCAP technology at five occasions during pregnancy (gestational weeks 10–12, 15–16, 25, 35 and 39), as well as at 2 and 12 months after delivery. Thirty-six women without and 20 women with allergic symptoms were included, of whom 13 were sensitised with allergic symptoms and 30 were non-sensitised without allergic symptoms. The levels of total IgE, but not allergen-specific IgE, were increased during early pregnancy when compared to 12 months after delivery in the sensitised women with allergic symptoms, but not in the non-sensitised women without allergic symptoms ( p < 0.01). This increase in total IgE levels during early pregnancy only in the sensitised women with allergic symptoms indicates that allergy is associated with an enhanced Th2 deviation during pregnancy.