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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 -
Frontiers in Immunology 2022The transcriptional regulation of B-cell response to antigen stimulation is complex and involves an intricate network of dynamic signals from cytokines and transcription... (Review)
Review
The transcriptional regulation of B-cell response to antigen stimulation is complex and involves an intricate network of dynamic signals from cytokines and transcription factors propagated from T-cell interaction. Long-term alloimmunity, in the setting of organ transplantation, is dependent on this B-cell response, which does not appear to be halted by current immunosuppressive regimens which are targeted at T cells. There is emerging evidence that shows that B cells have a diverse response to solid organ transplantation that extends beyond plasma cell antibody production. In this review, we discuss the mechanistic pathways of B-cell activation and differentiation as they relate to the transcriptional regulation of germinal center B cells, plasma cells, and memory B cells in the setting of solid organ transplantation.
Topics: B-Lymphocytes; Germinal Center; Graft Rejection; Histocompatibility; Organ Transplantation
PubMed: 36016958
DOI: 10.3389/fimmu.2022.895157 -
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 -
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 -
Transfusion Medicine Reviews Oct 2020Despite significant advancements in the production of platelet products, storage, and transfusion, transfusion refractoriness remains a significant clinical problem,... (Review)
Review
Despite significant advancements in the production of platelet products, storage, and transfusion, transfusion refractoriness remains a significant clinical problem, affecting up to 14% of hematological patients receiving platelet transfusions. Human leukocyte antigen (HLA) alloimmunization is a major cause of immune platelet refractoriness, and its rate can be significantly reduced by implementation of leukoreduction. Despite promising preclinical results, pathogen reduction does not reduce HLA alloimmunization. Patients with HLA alloimmune refractoriness are usually managed with HLA-selected platelet transfusions. In this review, we describe the pathophysiology of HLA alloimmunization and alloimmune refractoriness, as well as options to prevent and treat these transfusion complications. We discuss the evidence supporting these options and point out the outstanding gaps. Finally, we review the possible future directions for prevention and treatment of alloimmune refractoriness.
Topics: Blood Platelets; HLA Antigens; Humans; Isoantibodies; Platelet Count; Platelet Transfusion; Thrombocytopenia; Treatment Failure
PubMed: 33127210
DOI: 10.1016/j.tmrv.2020.09.010 -
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 -
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 -
American Journal of Transplantation :... Nov 2023Biological sex affects immunity broadly, with recognized effects on the incidence and severity of autoimmune diseases, infections, and malignancies. Consequences of sex... (Review)
Review
Biological sex affects immunity broadly, with recognized effects on the incidence and severity of autoimmune diseases, infections, and malignancies. Consequences of sex on alloimmunity and outcomes in solid organ transplantation are less well defined. Clinical studies have shown that donor and recipient sex independently impact transplant outcomes, which are further modified by aging. Potential mechanisms have thus far not been detailed and may include hormonal, genetic, and epigenetic components. Here, we summarize relevant findings in immunity in addition to studies in clinical and experimental organ transplantation detailing the effects of biological sex on alloimmunity. Understanding both clinical impact and mechanisms is expected to provide critical insights on the complexity of alloimmune responses, with the potential to fine-tune treatment and allocation while providing a rationale to include both sexes in transplant research.
Topics: Male; Female; Humans; Clinical Relevance; Graft Rejection; Organ Transplantation; Tissue Donors
PubMed: 37543092
DOI: 10.1016/j.ajt.2023.07.022 -
Transfusion Medicine and Hemotherapy :... Feb 2023Antibodies to human neutrophil alloantigens (HNA) are involved in the pathophysiology of several clinical conditions including transfusion-related acute lung injury...
BACKGROUND
Antibodies to human neutrophil alloantigens (HNA) are involved in the pathophysiology of several clinical conditions including transfusion-related acute lung injury (TRALI), alloimmune and autoimmune neutropenia, and febrile nonhemolytic transfusion reactions leading to neutropenia. The cognate antigens are polymorphic structures expressed on several glycoproteins on the neutrophils, i.e., antigens HNA-1a, -1b, -1c, and -1d on Fc-γ-receptor IIIb; HNA-2 on CD177; HNA-3a and -3b on choline transporter-like protein 2; HNA-4a and -4b on CD11b/αM subunit of the αMβ2-integrin (CD11b/CD18, Mac-1, CR3); and HNA-5a and -5b on αL-subunit (CD11a) of the αLβ2 integrin (CD11a/CD18), leukocyte function associated molecule (LFA)-1. Currently, there is a lacuna of diagnostic methods for detection of HNA in India. This study aimed to determine the HNA frequencies in Indians, estimate the risk of alloimmunization, and prepare typed neutrophil panels, which can be used to detect HNA antibodies in neutropenia cases.
MATERIAL AND METHODS
EDTA blood samples were collected from random 1,054 blood donors. HNA-2 was phenotyped on fresh EDTA samples using FITC labelled monoclonal anti-CD177 by flowcytometry. HNA-1 () genotyping was carried out by DNA sequencing and PCR-RFLP. Antigens of HNA-3 () and HNA-5 () were genotyped by PCR-RFLP using and restriction enzymes, respectively, while HNA-4 () was genotyped by PCR-SSP.
RESULTS
Allele frequencies of *, *, and * were found to be 0.433, 0.444, and 0.087, respectively. FCGR3B*01+*02+*03- was the most common genotype (33.78%). Ten individuals showed deficiency of FCGR3B individuals, while 23 showed hyperexpression, i.e., ***. *and * occurred with a frequency of 0.002 and 0.024. HNA-2 was found to be a high frequency antigen occurring in 98.8% population. Four percent individuals showed atypical expression of CD177 on their neutrophils. Allele frequencies of * and *were 0.812 and 0.188, respectively, and that of *, *, *, and * were 0.9546, 0.0454, 0.2372, and 0.7628, respectively.
CONCLUSION
This is the first study in India to report the frequencies of HNA among blood donors. Typed neutrophil panels identified in the present study will enable us to investigate suspected cases of immune neutropenia in future.
PubMed: 36818775
DOI: 10.1159/000525654 -
Blood Reviews May 2023FNAIT is a pregnancy-associated condition caused by maternal alloantibodies against paternally-inherited platelet antigens, most frequently HPA-1a on integrin β3. The... (Review)
Review
FNAIT is a pregnancy-associated condition caused by maternal alloantibodies against paternally-inherited platelet antigens, most frequently HPA-1a on integrin β3. The clinical effects range from no symptoms to fatal intracranial hemorrhage, but underlying pathophysiological determinants are poorly understood. Accumulating evidence suggests that differential antibody-Fc-glycosylation, activation of complement/effector cells, and integrin function-blocking effects contribute to clinical outcome. Furthermore, some antibodies preferentially bind platelet integrin αIIbβ3, but others bind αvβ3 on endothelial cells and trophoblasts. Defects in endothelial cells and angiogenesis may therefore contribute to severe anti-HPA-1a associated FNAIT. Moreover, anti-HPA-1a antibodies may cause placental damage, leading to intrauterine growth restriction. We discuss current insights into diversity and actions of HPA-1a antibodies, gathered from clinical studies, in vitro studies, and mouse models. Assessment of all factors determining severity and progression of anti-HPA-1a-associated FNAIT may importantly improve risk stratification and potentially reveal novel treatment strategies, both for FNAIT and other immunohematological disorders.
Topics: Animals; Mice; Pregnancy; Female; Humans; Thrombocytopenia, Neonatal Alloimmune; Placenta; Endothelial Cells; Blood Platelets; Isoantibodies
PubMed: 36581513
DOI: 10.1016/j.blre.2022.101038