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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 -
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 -
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 -
Current Opinion in Hematology Nov 2020The purpose of this review is to summarize the role of complement in regulating the removal of a target alloantigen following an incompatible red blood cell (RBC)... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to summarize the role of complement in regulating the removal of a target alloantigen following an incompatible red blood cell (RBC) transfusion, the formation of alloantibodies following RBC alloantigen exposure, and the development of hyperhemolysis in patients with sickle cell disease (SCD).
RECENT FINDINGS
Recent studies demonstrate that complement can accelerate alloantibody-mediated removal of target alloantigens from the RBC surface following incompatible transfusion. Complement also influences alloantigen availability during developing alloimmune responses and serves as a unique mediator of CD4 T-cell-independent alloantibody formation following RBC alloantigen exposure. Finally, alternative complement pathway activation appears to play a key role in the development of acute hemolytic episodes in patients with SCD, providing a potential druggable target to prevent acute complications in patients with this disease.
SUMMARY
Recent studies suggest that complement can regulate a wide variety of processes germane to hematology, from transfusion complications to baseline hemolysis in patients with SCD. As the role of complement in various disease processes becomes more fully understood, the ability to leverage recently developed complement modulating drugs will only continue to enhance providers' ability to favorably intervene in many hematological diseases.
Topics: Anemia, Hemolytic, Autoimmune; Animals; Blood Group Incompatibility; Complement System Proteins; Erythrocyte Transfusion; Erythrocytes; Hemolysis; Humans; Isoantibodies; Isoantigens
PubMed: 32889827
DOI: 10.1097/MOH.0000000000000610 -
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 -
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 -
Transfusion Clinique Et Biologique :... Aug 2015Red blood cell (RBC) alloimmunization can be a life-threatening complication for patients with sickle cell disease (SCD) receiving therapeutic transfusions. Despite... (Review)
Review
Red blood cell (RBC) alloimmunization can be a life-threatening complication for patients with sickle cell disease (SCD) receiving therapeutic transfusions. Despite provision of extended antigen-matched donor RBCs, patients continue to develop antibodies due to high degree of polymorphisms in the immunogenic antigens in individuals of African ancestry. Identification of biomarkers of alloimmunization in this patient population is therefore of great interest and will help to identify in advance patients most likely to make antibodies in response to transfusion. We have recently identified altered T cell responses and innate immune abnormalities in alloimmunized SCD patients. In this paper, we summarize this work and propose our working model of how innate immune abnormalities can contribute to pathogenic T cell responses in alloimmunized SCD patients. We believe that unravelling the basis of such altered interactions at the cellular and molecular level will help future identification of biomarkers of alloimmunization with the goal that this information will ultimately help guide therapy in these patients.
Topics: Anemia, Sickle Cell; B-Lymphocytes; Biomarkers; Blood Group Incompatibility; Erythrocyte Transfusion; Erythrocytes; Heme; Heme Oxygenase-1; Hemin; Humans; Interleukin-10; Interleukin-12; Isoantibodies; Lymphocyte Cooperation; Membrane Proteins; Models, Immunological; Monocytes; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Transfusion Reaction
PubMed: 26056038
DOI: 10.1016/j.tracli.2015.05.005 -
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 -
Hematology. American Society of... Dec 2016Red blood cell (RBC) transfusions are critical for treatment and prevention of complications of sickle cell disease (SCD), and most SCD patients will receive 1 or more... (Review)
Review
Red blood cell (RBC) transfusions are critical for treatment and prevention of complications of sickle cell disease (SCD), and most SCD patients will receive 1 or more transfusions by age 20. However, SCD alloimmunization remains a serious complication of transfusions that can lead to life-threatening acute and delayed transfusion reactions. Alloimmunization rates are higher in SCD patients most likely due to RBC antigenic differences between largely white donors vs mainly African-American recipients and frequency of transfusions. However, it remains unclear why some but not all SCD patients develop alloantibodies. Cellular immune responses that differ between alloimmunized and nonalloimmunized SCD patients are beginning to be characterized. Altered CD4 T helper cell responses, known to control immunoglobulin G production, have been identified in alloimmunized SCD patients, including abnormalities in regulatory T cells, as well as helper type 1 (T1), T17, and follicular helper T cells. Furthermore, heightened innate immune cell responses to cell free heme with cell polarization toward proinflammatory T cell profiles were recently reported in SCD antibody responders, suggesting that the ongoing hemolytic state in SCD may impair the ability of innate immune cells in these already alloimmunized patients to counter alloimmunization. Identification of molecular pathways in key cellular components that differ between alloimmunized and nonalloimmunized SCD patients is likely to lead to identification of biomarkers of alloimmunization and future design of targeted therapies to prevent or even dampen alloantibody responses in these highly susceptible patients.
Topics: Anemia, Sickle Cell; Animals; Erythrocyte Transfusion; Erythrocytes; Humans; Immunization; Isoantibodies; Isoantigens; Th1 Cells; Th17 Cells
PubMed: 27913516
DOI: 10.1182/asheducation-2016.1.457 -
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