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Indian Journal of Pediatrics Dec 2020In spite of advances in medical science, Rh alloimmunisation remains one of the leading causes of preventable neuro-morbidities and significant neonatal... (Review)
Review
In spite of advances in medical science, Rh alloimmunisation remains one of the leading causes of preventable neuro-morbidities and significant neonatal hyperbilirubinemia in lower-middle income countries. Despite availability of effective antenatal preventive strategy (Anti-D), its uptake in antenatal period is low due to ignorance. Further, once diagnosed, there is lack of adequate antenatal follow up in health care facility. Some of these cases even remain undiagnosed in antenatal period only to present as a case of severe hyperbilirubinemia and kernicterus in late neonatal period. Thus, there is an urgent need for creating awareness and educating health care professionals for early detection and timely management in both antenatal and postnatal period. Following two doses of anti-D prophylaxis (one in antenatal period and one in immediate postnatal period) the incidence of Rh alloimmunisation can reduce to <1%. It is recommended to follow all Rh alloimmunised pregnancies antenatally with serial indirect Coombs test titre (till critical titre is reached) followed by serial Doppler velocimetry of middle cerebral artery in a perinatal centre where facility for intrauterine transfusion as well as advanced neonatal care is available. Postnatal management of these infants comprises of confirmation of diagnosis, aggressive phototherapy and in selective cases, double volume exchange transfusion. With appropriate antenatal and postnatal management, the prognosis of Rh alloimmunised pregnancy remains favourable and long term outcome of Rh alloimmunised infants remain comparable with their normal counterparts.
Topics: Anemia, Hemolytic, Autoimmune; Exchange Transfusion, Whole Blood; Female; Humans; Hyperbilirubinemia, Neonatal; Infant, Newborn; Phototherapy; Pregnancy; Rh Isoimmunization
PubMed: 32607667
DOI: 10.1007/s12098-020-03366-0 -
Maedica Dec 2021RhD alloimmunization remains a severe problem worldwide, but its management has been revolutionized by two important discoveries: the possibility to establish fetal Rh...
RhD alloimmunization remains a severe problem worldwide, but its management has been revolutionized by two important discoveries: the possibility to establish fetal Rh genotype non-invasively by using a maternal blood sample, and using of Doppler velocimetry to monitor early signs of affected fetuses. We performed a literature review by searching PubMed for relevant information about diagnosis, prognosis, and management of secondary affected Rh alloimmunized pregnancies. The risk to develop fetal anemia and hydrops seems to increase with increasing concentrations of Rh antibodies, and studies show it is higher for subsequent pregnancies. Individuals presenting the DEL phenotype with the types 1, 2 or 3 can be considered RhD positive and anti-D immune globulin is not indicated. Medical algorithm involves previous pregnancy history together with serum parameters. Follow-up in a department of maternal fetal medicine is desired and encouraged in these cases. Depending on the severity and woman's previous pregnancy history, especially condition prior to 24 weeks of gestation, several therapies such as plasmaphereses, intravenous immune globulin or intrauterine transfusions can be conducted. Intrauterine transfusions have a better prognosis when performed earlier and on fetuses without hydrops. Although the incidence of hemolytic disease of the fetus and newborn has decreased and is no longer a major cause of perinatal mortality, vigilance is still required. There is a strong argument for reunite the management of these cases in dedicated maternal fetal medicine centers that perform invasive procedures in order to improve knowledge, gain skills and enhance clinical management.
PubMed: 35261671
DOI: 10.26574/maedica.2020.16.4.681 -
Journal of Immunological Methods Feb 2022Antibody-mediated rejection is a major cause of graft failure in organ transplantation. For this reason, B cell responses are of particular interest to transplantation...
Antibody-mediated rejection is a major cause of graft failure in organ transplantation. For this reason, B cell responses are of particular interest to transplantation research. Rats are important model organisms for transplant studies, but B cell alloimmune assays and B cell subset markers are poorly established in rats. We alloimmunized rats by donor blood injection using the high responder rat strain combination Brown Norway (donor) and Lewis (recipient) rats. Using splenocytes from alloimmunized and control rats, we established assays to assess allospecific B cell proliferation and the capacity to generate allospecific B memory cells and alloantibody-secreting cells after antigenic rechallenge in vitro using a mixed lymphocyte reaction. Furthermore, we defined a simple gating and sorting strategy for pre- and post-germinal center follicular B cells, as well as non-switched and switched plasmablasts. Our protocols for assessing B cell alloresponses and B cell subsets in rats may help to accelerate research into the role of B cells and manipulation of humoral alloresponses in transplant research.
Topics: Animals; B-Lymphocytes; Cell Proliferation; Cells, Cultured; Graft Rejection; Immunity, Humoral; Immunologic Memory; Isoantibodies; Isoantigens; Lymphocyte Activation; Male; Memory B Cells; Phenotype; Rats, Inbred BN; Rats, Inbred Lew; Rats
PubMed: 34971633
DOI: 10.1016/j.jim.2021.113212 -
Transfusion Clinique Et Biologique :... Aug 2020Red blood cell alloimmunisation after transfusion of red blood cell concentrates carries a risk for every recipient. This risk is particularly high for patients with... (Review)
Review
Red blood cell alloimmunisation after transfusion of red blood cell concentrates carries a risk for every recipient. This risk is particularly high for patients with conditions such as sickle cell disease. However, red blood cell alloimmunisation can also occur after platelet concentrate transfusion. All blood group systems other than ABO are affected, and there are several mechanisms responsible for this alloimmunisation. The practical implications of this are a need to match red blood cell concentrates in all alloimmunised patients and, in pregnant women, recongnition of the risk of developing haemolytic disease of the foetus and newborn. Several measures can be taken to prevent alloimmunisation: in the case of the D antigen, for example, anti-RhD immunoglobulins can be infused before transfusing platelet concentrates from an RhD-positive donor in a RhD-negative recipient.
Topics: Antigens, Surface; Blood Group Antigens; Blood Group Incompatibility; Blood Grouping and Crossmatching; Blood Platelets; Cell-Derived Microparticles; Erythrocytes; Female; Humans; Inflammation; Isoantibodies; Male; Platelet Transfusion; Pregnancy; Pregnancy Complications; Rh Isoimmunization; Rh-Hr Blood-Group System; Rho(D) Immune Globulin
PubMed: 32544526
DOI: 10.1016/j.tracli.2020.06.001 -
Blood Reviews Nov 2023Platelet transfusion refractoriness due to HLA alloimmunization presents a significant medical problem, particularly among multiply transfused patients with hematologic... (Review)
Review
Platelet transfusion refractoriness due to HLA alloimmunization presents a significant medical problem, particularly among multiply transfused patients with hematologic malignancies and those undergoing hematopoietic stem cell transplants. HLA compatible platelet transfusions also impose significant financial burden on these patients. Recently, several novel mechanisms have been described in the development of HLA alloimmunization and platelet transfusion refractoriness. We review the history of platelet transfusions and mechanisms of HLA-sensitization and transfusion refractoriness. We also summarize advances in the diagnosis and treatment of platelet transfusion refractoriness due to HLA alloimmunization.
Topics: Humans; Platelet Transfusion; Isoantibodies; Thrombocytopenia; Blood Transfusion; Hematologic Neoplasms; Anemia, Hemolytic, Autoimmune; HLA Antigens; Blood Platelets
PubMed: 37805287
DOI: 10.1016/j.blre.2023.101135 -
Journal of Clinical Medicine May 2020: Incompatibilities between the mother and unborn baby can cause complications that must be identified early to initiate the appropriate treatment. For example, neonatal... (Review)
Review
: Incompatibilities between the mother and unborn baby can cause complications that must be identified early to initiate the appropriate treatment. For example, neonatal alloimmune thrombocytopenia (NAIT), neonatal alloimmune neutropenia (NAIN), and morbus hemolyticus neonatorum affect children worldwide. : This literature review aims to depict the similarities and differences between these three disorders from a clinical and mechanistic point of view. : The current literature review entailed conducting a systematic search to locate articles on the three conditions. Different electronic databases, including PsycINFO, PubMed, Web of Science, and CINAHL, were searched using the search terms "neonatal alloimmune thrombocytopenia", "neonatal alloimmune neutropenia", "morbus hemolyticus neonatorum", "NAIT", "FNAIT", "fetal", "NAIN", and "hemolytic disease of the newborn". : This review shows that these three diseases are caused by incompatibilities between the maternal and fetal immune systems. Furthermore, these conditions can lead to severe complications that hinder fetal development and cause death if not well managed. Discussion: The current literature review shows that NAIT, NAIN, and morbus hemolyticus neonatorum are rare conditions that occur when the mother produces antibodies against the fetal immune system. Thus, there is a need for the early detection of these conditions to initiate appropriate treatment before the child experiences adverse effects. : The development of NAIT, NAIN, and morbus hemolyticus neonatorum is linked to the production of antibodies against the fetal immune system and fetal antigens. Further studies are required to determine potential interventions to reduce the risk of developing these three conditions.
PubMed: 32422924
DOI: 10.3390/jcm9051470 -
Circulation Research Sep 2020Transplant arteriosclerosis is the major limitation to long-term survival of solid organ transplantation. Although both immune and nonimmune cells have been suggested to...
RATIONALE
Transplant arteriosclerosis is the major limitation to long-term survival of solid organ transplantation. Although both immune and nonimmune cells have been suggested to contribute to this process, the complex cellular heterogeneity within the grafts, and the underlying mechanisms regulating the disease progression remain largely uncharacterized.
OBJECTIVE
We aimed to delineate the cellular heterogeneity within the allografts, and to explore possible mechanisms underlying this process.
METHODS AND RESULTS
Here, we reported the transcriptional profiling of 11 868 cells in a mouse model of transplant arteriosclerosis by single-cell RNA sequencing. Unbiased clustering analyses identified 21 cell clusters at different stages of diseases, and focused analysis revealed several previously unknown subpopulations enriched in the allografts. Interestingly, we found evidence of the local formation of tertiary lymphoid tissues and suggested a possible local modulation of alloimmune responses within the grafts. Intercellular communication analyses uncovered a potential role of several ligands and receptors, including and , in regulating lymphatic endothelial cell-induced early chemotaxis and infiltration of immune cells. In vivo mouse experiments confirmed the therapeutic potential of CCL21 and CXCR3 neutralizing antibodies in transplant arteriosclerosis. Combinational use of genetic lineage tracing and single-cell techniques further indicate the infiltration of host-derived c-Kit stem cells as heterogeneous populations in the allografts. Finally, we compared the immune response between mouse allograft and atherosclerosis models in single-cell RNA-seq analysis. By analyzing susceptibility genes of disease traits, we also identified several cell clusters expressing genes associated with disease risk.
CONCLUSIONS
Our study provides a transcriptional and cellular landscape of transplant arteriosclerosis, which could be fundamental to understanding the initiation and progression of this disease. CCL21/CXCR3 was also identified as important regulators of immune response and may serve as potential therapeutic targets in disease treatment.
Topics: Animals; Aorta; Arteriosclerosis; Cell Lineage; Chemokine CCL21; Disease Models, Animal; Female; Gene Expression Profiling; Graft Survival; Immunity, Cellular; Immunity, Innate; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Proto-Oncogene Proteins c-kit; RNA-Seq; Receptors, CXCR3; Single-Cell Analysis; Time Factors; Transcriptome; Transplantation Tolerance
PubMed: 32689904
DOI: 10.1161/CIRCRESAHA.119.316470 -
Transfusion and Apheresis Science :... Feb 2020Non-invasive fetal HPA-1a typing is a valuable tool to identify the pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT). At present, prenatal... (Review)
Review
Non-invasive fetal HPA-1a typing is a valuable tool to identify the pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT). At present, prenatal determination of the fetus HPA-1a type is performed for diagnostic purposes in pregnancies of HPA-1 alloimmunized women with history of a previous fetus or child with FNAIT. Different approaches have been used to determine the fetal HPA-1a genotype from cell-free fetal DNA (cffDNA) in the mother's plasma, mainly based on real-time PCR. Due to the single nucleotide polymorphism (SNP) between the HPA-1a and HPA-1b allelic sequences, a robust and accurate detection of the fetal genotype is challenging, and the sensitivity of most assays is still limited early in pregnancy. Nowadays, the availability of technologies such as next generation sequencing (NGS) or digital PCR offers unprecedented possibilities of analyzing cell-free DNA (cfDNA)-amplified sequences with very high coverage and high sensitivity. In addition, other interesting approaches using variant sequence enrichment strategies have been recently described. In particular, coamplification at lower denaturation temperature PCR (COLD-PCR) offers a simple and sensitive strategy for noninvasive fetal HPA-1 typing. These novel approaches are explained in more detail in this review. Despite no population-based FNAIT screening programs have so far been implemented, the perspectives in terms of treatment and prevention are changing and less costly high-throughput maternal HPA-1a typing methods have been developed. Altogether, this may lead to the implementation of fetal HPA-1a typing with a broader scope in the future, playing a critical role within FNAIT screening programs.
Topics: Antigens, Human Platelet; Female; Fetus; Humans; Integrin beta3; Pregnancy; Thrombocytopenia, Neonatal Alloimmune
PubMed: 31953107
DOI: 10.1016/j.transci.2019.102708 -
Prenatal Diagnosis Aug 2020Management of maternal red cell alloimmunization has been revolutionized over the last 60 years. Advances in the prevention, screening, diagnosis, and treatment of... (Review)
Review
Management of maternal red cell alloimmunization has been revolutionized over the last 60 years. Advances in the prevention, screening, diagnosis, and treatment of alloimmune-induced fetal anemia make this condition an exemplar for contemporary practice in fetal therapy. Since survival is now an expectation, attention has turned to optimization of long-term outcomes following an alloimmunized pregnancy. In this review, the current management of red cell alloimmunization is described. Current research and future directions are discussed with particular emphasis on later life outcomes after alloimmune fetal anemia.
Topics: Blood Transfusion, Intrauterine; Erythroblastosis, Fetal; Female; Fetal Diseases; History, 21st Century; Humans; Pregnancy; Prenatal Care; Prenatal Exposure Delayed Effects; Rh Isoimmunization
PubMed: 32108353
DOI: 10.1002/pd.5674 -
Seminars in Thrombosis and Hemostasis Jun 2023Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a common cause of severe thrombocytopenia in newborns. Intracranial bleeding may lead to severe neurological... (Review)
Review
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a common cause of severe thrombocytopenia in newborns. Intracranial bleeding may lead to severe neurological sequelae and mortality. Current management of pregnancies at risk is suboptimal. Prenatal FNAIT diagnosis commonly requires invasive procedures and therapy is associated with a high treatment burden. The present review explores advances in the field and their potential contribution to modification of the diagnostic and therapeutic landscape. Topics addressed include the role of noninvasive prenatal testing using fetal cell free DNA, insights into novel and prospective therapeutic options achieved through the development of murine models of FNAIT as well as the forecast for the progress in pregnancy risk stratification through advancement in the investigation of biological characteristics of alloantibodies and their association with the risk of fetal bleeding.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Animals; Mice; Thrombocytopenia, Neonatal Alloimmune; Fetal Diseases; Prenatal Care; Prenatal Diagnosis; Hemorrhage; Antigens, Human Platelet
PubMed: 36368687
DOI: 10.1055/s-0042-1757900