Did you mean: alloimmunization
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Archivos Argentinos de Pediatria Jun 2021Thrombocytopenia, defined as a platelet count below 100 x 109/L, is a very common finding in the neonatal period, especially in critically ill infants and preterm... (Review)
Review
Thrombocytopenia, defined as a platelet count below 100 x 109/L, is a very common finding in the neonatal period, especially in critically ill infants and preterm newborns. Its causes are multiple: it may be due both to pediatric conditions and to other factors involved in the fetal-placental-maternal interface. This initial article describes the causes of thrombocytopenia, proposes a diagnostic approach to manage a thrombocytopenic newborn infant, and provides a detailed description of the different conditions corresponding to thrombocytopenia of immune etiology. It also describes the different causative mechanisms and reviews the varying characteristics of thrombocytopenia secondary to maternal immune thrombocytopenia and neonatal alloimmune thrombocytopenia. The different treatment approaches to each of the different conditions are described both for their pre- as well as their postnatal management. The severity of thrombocytopenia and the serious complications and sequelae associated with the neonatal alloimmune thrombocytopenia are highlighted.
Topics: Diagnosis, Differential; Female; Humans; Infant; Infant, Newborn; Placenta; Platelet Count; Pregnancy; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia, Neonatal Alloimmune
PubMed: 34033425
DOI: 10.5546/aap.2021.eng.e202 -
Blood Apr 2019Blood transfusion is the most common procedure completed during a given hospitalization in the United States. Although often life-saving, transfusions are not risk-free.... (Review)
Review
Blood transfusion is the most common procedure completed during a given hospitalization in the United States. Although often life-saving, transfusions are not risk-free. One sequela that occurs in a subset of red blood cell (RBC) transfusion recipients is the development of alloantibodies. It is estimated that only 30% of induced RBC alloantibodies are detected, given alloantibody induction and evanescence patterns, missed opportunities for alloantibody detection, and record fragmentation. Alloantibodies may be clinically significant in future transfusion scenarios, potentially resulting in acute or delayed hemolytic transfusion reactions or in difficulty locating compatible RBC units for future transfusion. Alloantibodies can also be clinically significant in future pregnancies, potentially resulting in hemolytic disease of the fetus and newborn. A better understanding of factors that impact RBC alloantibody formation may allow general or targeted preventative strategies to be developed. Animal and human studies suggest that blood donor, blood product, and transfusion recipient variables potentially influence which transfusion recipients will become alloimmunized, with genetic as well as innate/adaptive immune factors also playing a role. At present, judicious transfusion of RBCs is the primary strategy invoked in alloimmunization prevention. Other mitigation strategies include matching RBC antigens of blood donors to those of transfusion recipients or providing immunomodulatory therapies prior to blood product exposure in select recipients with a history of life-threatening alloimmunization. Multidisciplinary collaborations between providers with expertise in transfusion medicine, hematology, oncology, transplantation, obstetrics, and immunology, among other areas, are needed to better understand RBC alloimmunization and refine preventative strategies.
Topics: ABO Blood-Group System; Blood Group Incompatibility; Erythrocyte Transfusion; Erythrocytes; Humans; Isoantibodies; Transfusion Reaction
PubMed: 30808636
DOI: 10.1182/blood-2018-08-833962 -
Transfusion Medicine and Hemotherapy :... Apr 2020Alloimmunization is caused by exposure to erythrocytes from a donor that expresses blood group antigens other than those of the recipient and is related to processes...
INTRODUCTION
Alloimmunization is caused by exposure to erythrocytes from a donor that expresses blood group antigens other than those of the recipient and is related to processes that alter the balance of the immune system. Knowing the pathophysiology of alloimmunization process is essential to understand clinical complications associated with this process.
PATIENTS AND METHODS
From October 2016 to April 2017, irregular antibody screening was performed in 1,434 polytransfused (compatible with the ABO and D system) patients by means of agglutination techniques using erythrocytes of a known phenotype of 44 patients with a positive alloantibody screening. Non-alloimmunized (control) subjects were matched for age, gender, pathology, and treatment group with alloimmunized patients. The subsets of B, T, and Treg lymphocytes were determined by flow cytometry.
RESULTS
The results of screening for alloantibodies in patients by specificity of antibodies were as follows: nonspecific (30%), followed by anti-Di (13%), anti-e (9%), anti-S (9%), anti-I (7%), anti-K (7%), and anti-P (7%). A lower percentage of CD4+ T lymphocytes and an increase of CD8+ T lymphocytes were observed in alloimmunized patients, as well as a low CD4/CD8 ratio (0.7 vs. 1.6, = 0.003), a higher percentage of B lymphocytes versus the control group (30 vs. 20%, = 0.003), and a decrease of Treg CD4+ lymphocytes versus the control group (3 vs. 12 cells/μL, = 0.043). These observations suggest that alloimmunized patients have important alterations in the number of some lymphocyte subsets that can be translated into clinical immune dysregulation.
CONCLUSION
A decreased CD4/CD8 ratio, increased B lymphocytes, and Treg lymphocyte deficiency are the most significant changes observed in alloimmunized patients.
PubMed: 32355475
DOI: 10.1159/000501861 -
Immunological Reviews Mar 2014Vertebrates mount strong adaptive immune responses to transplanted organs (allografts), but the mechanisms by which the innate immune system initiates this response are... (Review)
Review
Vertebrates mount strong adaptive immune responses to transplanted organs (allografts), but the mechanisms by which the innate immune system initiates this response are not completely understood. In anti-microbial immunity, non-self molecules associated with pathogens but not present in the host induce the maturation of innate antigen-presenting cells (APCs) by binding to germ-line-encoded receptors. Mature APCs then initiate the adaptive immune response by presenting microbial antigen and providing costimulatory signals to T cells. How allografts activate APCs, however, is less clear, because allografts are presumably sterile. A widely accepted view is that inflammatory or 'danger' molecules released by dying graft cells at the time of transplantation trigger APC maturation and the T-cell response that follows. Alternatively, it has been proposed that the introduction of microbial products during the surgical procedure could also alert the innate immune system to the presence of the transplanted organ. Here, we review why these hypotheses fail to fully explain how the alloimmune response is initiated after transplantation and summarize evidence that recognition of allogeneic non-self by monocytes is a key event in triggering alloimmunity and graft rejection.
Topics: Allografts; Animals; Antigen-Presenting Cells; Graft Rejection; Graft Survival; Humans; Immunity, Innate; Molecular Sequence Data; Organ Transplantation; Transplantation Tolerance; Treatment Outcome
PubMed: 24517431
DOI: 10.1111/imr.12153 -
Transplantation Aug 2022Eosinophils are bone-marrow-derived granulocytes known for their ability to facilitate clearance of parasitic infections and their association with asthma and other... (Review)
Review
Eosinophils are bone-marrow-derived granulocytes known for their ability to facilitate clearance of parasitic infections and their association with asthma and other inflammatory diseases. The purpose of this review is to discuss the currently available human observational and animal experimental data linking eosinophils to the immunologic response in solid organ transplantation. First, we present observational human studies that demonstrate a link between transplantation and eosinophils yet were unable to define the exact role of this cell population. Next, we describe published experimental models and demonstrate a defined mechanistic role of eosinophils in downregulating the alloimmune response to murine lung transplants. The overall summary of this data suggests that further studies are needed to define the role of eosinophils in multiple solid organ allografts and points to the possibility of manipulating this cell population to improve graft survival.
Topics: Animals; Eosinophils; Graft Survival; Humans; Lung Transplantation; Mice; Organ Transplantation; Transplantation, Homologous
PubMed: 34966103
DOI: 10.1097/TP.0000000000004030 -
Blood Transfusion = Trasfusione Del... Jul 2021Red blood cell (RBC) transfusion remains an essential part of sickle cell disease (SCD) management but it can lead to alloimmunisation, with an increased incidence in...
Complete RH and Kell matching related to low alloimmunisation risk in sickle cell disease: prevalence and risk factors of alloimmunisation in a Spanish Tertiary Care National Reference Centre.
BACKGROUND
Red blood cell (RBC) transfusion remains an essential part of sickle cell disease (SCD) management but it can lead to alloimmunisation, with an increased incidence in this population. Prevention is based on RBC antigen phenotype matching, with complete RH and Kell matching being a standard of care.
MATERIALS AND METHODS
We performed a retrospective, single-centre study analysing alloimmunisation prevalence and risk factors in a cohort of transfused SCD patients.
RESULTS
Eighty-seven patients (96.5% of paediatric age) received 1,781 RBC units (RBCu). Complete RH and Kell matched RBCu represented a median of 100% among total transfusions per patient. Of the 87 patients, 52 (59.8%) underwent chronic transfusion therapy, whereas 35 (40.2%) were only episodically transfused. Seven patients were alloimmunised (8.4%) and eleven antibodies were detected (alloimmunisation rate: 0.62/100 units transfused). 54.6% of these antibodies corresponded to RH-Kell despite the high accomplishment of the RH-Kell matching transfusion protocol. Alloimmunised patients had a median of 90.9% RH-Kell matched transfusions vs 100% in non-alloimmunised patients, but no statistical differences were observed (p=0.127). Number of transfused RBCu (19 vs 7; p=0.023), number of episodic RBCu (8 vs 2; p=0.006), episodic to chronic RBCu ratio (0.57 vs 0.09; p=0.045), number of vaso-occlusive crises (VOC) (4 vs 2; p=0.011), and autoantibody presence (57.1 vs 0%; p<0.001) were all statistically related to alloimmunisation.
DISCUSSION
We report a low alloimmunisation prevalence (8.4%) related to a high grade of RH-Kell matching. However, deviation from 100% translates into alloimmunisation, with >50% of alloantibodies corresponding to RH-Kell. Alloimmunisation risk increases with transfusion burden, particularly during acute complications, and in patients with a higher number of VOC, probably reflecting underlying inflammation and disease severity. Further studies will be needed to elucidate additional risk factors and help prevent alloimmunisation in these patients.
Topics: Anemia, Sickle Cell; Child; Erythrocytes; Humans; Isoantibodies; Prevalence; Retrospective Studies; Risk Factors; Tertiary Healthcare
PubMed: 33085598
DOI: 10.2450/2020.0096-20 -
Frontiers in Immunology 2018
Topics: Endothelial Cells; Endothelium, Vascular; Graft Rejection; Histocompatibility; Humans; Inflammation; Isoantibodies; Organ Transplantation
PubMed: 30581438
DOI: 10.3389/fimmu.2018.02886 -
Transplantation Jan 2014Microbial products can be recognized by pattern recognition receptors expressed by immune and parenchymal cells and drive innate immunity that can in turn shape adaptive... (Review)
Review
Microbial products can be recognized by pattern recognition receptors expressed by immune and parenchymal cells and drive innate immunity that can in turn shape adaptive immune responses to microbial and transplant antigens. In transplanted patients, the signals and their downstream inflammatory cytokines elicited in response to infections can modulate ongoing alloimmune responses and modify the fate of transplanted organs. In recent years, it has become apparent that microbial signals can be generated not only by active pathogenic infections but also by commensal microbiota, thus opening a new field of research into the interplay between the microbiota and the immune system in homeostasis and disease. The wide use of antibiotics and immunosuppressive drugs in transplanted patients can have dramatic consequences on the microbiota that can in turn shape immune responses and perhaps alloresponses, whereas the ongoing immune responses can in turn affect the commensal or pathogenic microorganisms in a feed-forward circle. Here, we discuss known and hypothesized mechanisms for how infections or microbiota-derived signals may affect local or systemic alloimmunity and briefly review data on downstream effects of antibiotics and vaccinations.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Vaccines; Graft Rejection; Graft Survival; Humans; Immunologic Memory; Immunosuppressive Agents; Organ Transplantation; T-Lymphocytes; Transplantation Tolerance; Transplantation, Homologous; Treatment Outcome
PubMed: 23903013
DOI: 10.1097/TP.0b013e3182a2037f -
Frontiers in Immunology 2020Autoimmune manifestations after allogeneic hematopoietic stem cell transplantation (AHSCT) are rare and poorly understood due to the complex interplay between the... (Review)
Review
Autoimmune manifestations after allogeneic hematopoietic stem cell transplantation (AHSCT) are rare and poorly understood due to the complex interplay between the reconstituting immune system and transplant-associated factors. While autoimmune manifestations following AHSCT have been observed in children with graft-versus-host disease (GvHD), an alloimmune process, they are distinct from the latter in that they are generally restricted to the hematopoietic compartment, i.e., autoimmune hemolytic anemia, thrombocytopenia, and/or neutropenia. Autoimmune cytopenias in the setting of ASHCT represent a donor against donor immune reaction. Non-hematologic autoimmune conditions in the post-AHSCT setting have been described and do not currently fall under the GvHD diagnostic criteria, but could represent alloimmunity since they arise from the donor immune attack on the antigens that are shared by the donor and host in the thyroid, peripheral and central nervous systems, integument, liver, and kidney. As in the non-transplant setting, autoimmune conditions are primarily antibody mediated. In this article we review the incidence, risk factors, potential pathophysiology, treatment, and prognosis of hematologic and non-hematologic autoimmune manifestations in children after AHSCT.
Topics: Anemia, Hemolytic, Autoimmune; Animals; Autoimmunity; Cell Self Renewal; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Histocompatibility; Humans; Transplantation Conditioning; Transplantation, Homologous
PubMed: 32983144
DOI: 10.3389/fimmu.2020.02017 -
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