Allo immunization and pregnancy

Hemolytic disease of newborn (HDN) is a condition that develops in a fetus, when the IgG molecules produced by the mother pass through the placenta and attack the fetal red blood cells. HDN can occur due to Rh and ABO incompatibilities between the mother and the fetus as well as due to other allo-immune antibodies belonging to Kell (K and k), Duffy (Fya), Kidd (Jka and Jkb), and MNS (M, N, S, and s) systems. Role of intravenous immunoglobulin in management of HDN is not clear.SARA red blood cell antigen, first discovered in 1990 is a low frequency antigen...

Transplant recipients can be sensitized against allo-HLA antigens by previous transplantation, blood transfusion, or pregnancy. While there is growing awareness that multiple components of the immune system can act as effectors of the alloresponse, the role of infectious pathogen exposure in triggering sensitization and allograft rejection has remained a matter of much debate. Here, we describe that exposure to pathogens may enhance the immune response to allogeneic HLA antigens via different pathways. The potential role of allo-HLA cross-reactivity of virus-specific memory T cells, activation of innate immunity leading to a more efficient induction of the adaptive alloimmune response by antigen-presenting cells, and bystander activation of existing memory B cell activation will be discussed in this review...

Immunological adjustments are needed to accommodate the close contact between two genetically different individuals, the mother and her baby, during mammalian pregnancy. Contact occurs between fetal somatic or placental cells that enter the maternal systemic circulation or between uterine immune cells and the invading extravillous trophoblast. Here we discuss two main types of maternal allo-recognition of the fetus. One depends on avoidance of maternal T cells recognizing and responding to paternally-derived non-self human leukocyte antigens class I and class I allotypes...

BACKGROUND: Human leukocyte antigen (HLA) allo-immunization is caused by various events such as blood transfusions, pregnancies, or organ transplantations, which can lead to sensitization. In this retrospective study, we evaluated different sensitization models and their effects on panel-reactive antibody (PRA) profiles of renal transplantation candidates. METHODS: Anti-HLA class I/II antibody screening tests were performed in 906 renal transplantation candidates with the use of a microbead-based assay (Luminex)...

To establish a healthy pregnancy the maternal immune system must tolerate fetal allo-antigens, yet remain competent to respond to infections. The ability of decidual NK cells (dNK) to promote migration of fetal extravillous trophoblasts (EVT) and placental growth as well as the capacity of EVT to promote immune tolerance are topics of high interest and extensive research. However, the problem of how dNK and decidual CD8+ T cells (CD8+ dT) provide immunity to infections of the placenta and the mechanisms that regulate their cytolytic function has thus far largely been ignored...

Innate immunity, which is unable to discriminate self from allo-antigens, is thought to be important players in the induction of miscarriages. Here, we show that the administration of IL-12 to syngeneic-mated C57BL/6 mice on gestation day 7.5 (Gd 7.5), drives significant miscarriages in pregnant females. Furthermore, the administration on Gd 7.5 of α-galactosylceramide (α-GalCer), which is known to activate invariant natural killer T (iNKT) cells, induced miscarriages in both syngeneic-mated C57BL/6 mice and allogeneic-mated mice (C57BL/6 (♀) × BALB/c (♂))...

Trans-placental cell trafficking is a naturally occurring process during pregnancy that results in the direct recognition of foreign maternal antigens by fetal tissue and vice versa. Immigration of potentially harmful allo-reactive maternal T cells into fetal circulation may provoke anti-fetal immune responses. However, the contact with fetal tissue may favor differentiation of maternal immune cells into cells with a regulatory phenotype. Human Umbilical Vein Endothelial Cells (HUVECs) possess immune-regulating properties and are one of the first fetal cells to get in contact with foreign maternal immune cells...

PROBLEM: Increasing evidence suggests modulation of the maternal immune response to be essential for successful pregnancy. We studied the immunophenotypic profile and function of peripheral blood T lymphocytes in infertile women undergoing in vitro fertilization (IVF) and fertile control population. METHOD: We collected peripheral blood mononuclear cells (PBMC) from infertile patients with recurrent implantation failure (RIF), infertile patients with successful IVF (IVFs), and normal fertile women...

Platelet refractoriness is a serious complication for patients receiving recurrent platelet transfusions, which can be explained by non-immune and immune causes. Human Leukocyte Antigens (HLA) allo-immunization, especially against HLA class I, is the major cause for immune platelet refractoriness. To a lesser extent, allo-antibodies against specific Human Platelet Antigen (HPA) are also involved. Pregnancy, transplantation and previous transfusions can lead to allo-immune reaction against platelet antigens...

More than 50 red blood cell (RBC) alloantibodies are known to cause hemolytic disease of the fetus and newborn (HDFN).Although Rh immune globulin (RhiG) prophylaxis has significantly reduced the incidence of pregnancies complicated by anti-D, the need to detect and monitor maternal allo antibodies capable of causing HDFN is still a concern. The prevalence and specificity of these alloantibodies were determined. In this retrospective study, the prevalence and specificities of unexpected RBC alloantibodies known to cause HDFN in pregnant women at a tertiary-care facility during a 5-year period were compiled and analyzed...

Membranous nephropathy (MN) is a kidney disease characterized by deposition of immune complexes and complement on the outer aspect of the glomerular capillary wall. It is responsible for a loss of serum proteins in the urine and kidney failure. During the last ten years, considerable progress has occurred in the understanding of the molecular bases of the disease with the description of three distinct mechanisms in humans. In the neonatal allo-immune form, antibodies are directed against neutral endopeptidase (NEP), a podocyte antigen absent in the mothers who become immunized against this antigen expressed by placenta cells during pregnancy...

The maternal immune system needs to adapt to tolerate the semi-allogeneic conceptus. Since maternal allo-reactive lymphocytes are not fully depleted, other local/systemic mechanisms play a key role in altering the immune response. The Th1/Th2 cytokine balance is not essential for a pregnancy to be normal. The immune cells, CD4+CD25+Foxp3+, also known as regulatory T cells (Tregs), step in to regulate the allo-reactive Th1 cells. In this review we discuss the role of Tregs in foeto-maternal immune tolerance and in recurrent miscarriage as well as their potential use as a new target for infertility treatment...

Maternal-fetal alloimmunisation with antenatal glomerulopathies (FMAIG) is a recently described allo-immune disorder that results from the production of maternal antibodies which cross the placenta, bind to fetal glomerular podocytes and thereby cause renal dysfunction. The pathogenic antibodies are directed against CD10/neutral endopeptidase (NEP). The infant's mother is apparently healthy but is genetically NEP-deficient, and thus becomes immunized against CD10/NEP expressed by placental cells during her first pregnancy...

OBJECTIVES: To evaluate the prevention of fetomaternal rhesus-D allo-immunization between 2008 and 2010. This evaluation was a part of the continuous medical evaluation (CME) that is compulsory in French hospitals. It was carried out using the tools recommended by the Haute Autorité de santé. We followed the national guidelines for the prevention of fetomaternal rhesus-D allo-immunization as outlined in 2005 by the national French college of Obstetrics and Gynecology. MATERIALS AND METHODS: We audited 3926 consultations in the first four months of 2008...

A rare case of a low incidence red cell antigen causing severe fetal allo-immune red cell disease is presented. Discussion of how this can be diagnosed and successfully managed antenatally using middle cerebral artery Doppler ultrasound and maternal antibody titre levels for fetal surveillance and timing of intervention with intrauterine transfusion.

OBJECTIVES: Indications for fetal blood sampling (FBS) are getting more limited. In this context, we aimed to evaluate fetal loss and morbidity associated with FBS and to precise the predictive parameters for fetal complications. More than a retrospective evaluation of our practices, the final end point of our study was to better inform the patients coming to our centre. PATIENTS AND METHODS: Retrospective monocentric cohort (Canadian Task Force classification II-2) of the 99 FBS performed between April 2004 and June 2010 on 80 fetuses, after excluding the procedures done for termination of pregnancy...

The Institute of Hematology, Peking University, is the largest hematopoietic stem cell transplantation (HSCT) center in China. A total of 400 HSCTs performed in 2010 accounted for a quarter of all allogeneic HSCTs performed in China. The GIAC protocol, which uses HLA-mismatched/haploidentical blood or bone marrow transplantation without in vitro T-cell depletion, entails administration of granulocyte-colony stimulating factor (G-CSF) to all donors, intensified immunological suppression, and treatment with anti-human thymocyte immunoglobulin...

OBJECTIVES: Fetal rhesus D (RhD) status determination using circulating cell-free fetal DNA from maternal plasma or serum is now recognized in Europe as a reliable and useful tool. A few countries are presently using this test in their management policy of rhesus D negative patients. The objective of this study is to evaluate the impact of this test on the costs of managing RhD-negative pregnant women, whether or not they are allo-immunized. STUDY DESIGN: A prospective follow-up of rhesus D negative women during their pregnancy was performed in three French obstetric departments...

The mammalian fetuses are semi-allograft for mothers. Therefore the failure of immunological tolerance often causes pregnancy loss. Recently, the effects of helminthes therapy for immune mediated diseases have been reported. In the present study we employed the murine model to examine the therapeutic potential of the recombinant antigen from a nematoda parasite, Dirofilaria immitis for immune mediated pregnancy loss. Recombinant D. immitis polyproteins (rDiAg) had been cloned and selected by us for the strongest immuno-regulatory activities in parasite antigens...

Formation of the placenta is a crucial step in mammalian pregnancy. Apart from its function in ensuring an optimal supply of nutrients and oxygen to the fetus, the placenta is also the interface at which allo-recognition of invading trophoblast cells by the maternal immune system can potentially occur. We summarise here the "state of the art" on how variability of immune system genes that code for major histocompatibility complex (MHC) molecules and natural killer receptors (NKR) may impact on human placentation...