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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 -
Transfusion Feb 2011In April 2010, a working group sponsored by the National Heart, Lung, and Blood Institute was assembled to identify research strategies to improve our understanding of...
In April 2010, a working group sponsored by the National Heart, Lung, and Blood Institute was assembled to identify research strategies to improve our understanding of alloimmunization caused by the transfusion of allogeneic blood components and to evaluate potential approaches to both reduce its occurrence and manage its effects. Significant sequelae of alloimmunization were discussed and identified, including difficulties in maintaining chronic transfusion of red blood cells and platelets, hemolytic disease of the newborn, neonatal alloimmune thrombocytopenia, and rejection of transplanted cells and tissues. The discussions resulted in a consensus that identified key areas of future research and developmental areas, including genetic and epigenetic recipient factors that regulate alloimmunization, biochemical specifics of transfused products that affect alloimmunization, and novel technologies for high-throughput genotyping to facilitate extensive and efficient antigen matching between donor and recipient. Additional areas of importance included analysis of unappreciated medical sequelae of alloimmunization, such as cellular immunity and its effect upon transplant and autoimmunity. In addition, support for research infrastructure was discussed, with an emphasis on encouraging collaboration and synergy of animal models biology and human clinical research. Finally, training future investigators was identified as an area of importance. In aggregate, this communication provides a synopsis of the opinions of the working group on the above issues and presents both a list of suggested priorities and the rationale for the topics of focus. The areas of research identified in this report represent potential fertile ground for the medical advancement of preventing and managing alloimmunization in its different forms and mitigating the clinical problems it presents to multiple patient populations.
Topics: Adult; Animals; Antigens, Human Platelet; Blood Group Antigens; Blood Group Incompatibility; Cooperative Behavior; Female; Forecasting; Health Priorities; Humans; Infant, Newborn; Isoantibodies; Lymphocyte Subsets; Male; Models, Animal; National Heart, Lung, and Blood Institute (U.S.); Pregnancy; Research Personnel; Thrombocytopenia, Neonatal Alloimmune; Transfusion Reaction; Transplantation Immunology; United States
PubMed: 21251006
DOI: 10.1111/j.1537-2995.2010.03024.x -
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 -
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 -
Nature Reviews. Nephrology Aug 2016The development of post-transplantation antibodies against non-HLA autoantigens is associated with rejection and decreased long-term graft survival. Although our... (Review)
Review
The development of post-transplantation antibodies against non-HLA autoantigens is associated with rejection and decreased long-term graft survival. Although our knowledge of non-HLA antibodies is incomplete, compelling experimental and clinical findings demonstrate that antibodies directed against autoantigens such as angiotensin type 1 receptor, perlecan and collagen, contribute to the process of antibody-mediated acute and chronic rejection. The mechanisms that underlie the production of autoantibodies in the setting of organ transplantation is an important area of ongoing investigation. Ischaemia-reperfusion injury, surgical trauma and/or alloimmune responses can result in the release of organ-derived autoantigens (such as soluble antigens, extracellular vesicles or apoptotic bodies) that are presented to B cells in the context of the transplant recipient's antigen presenting cells and stimulate autoantibody production. Type 17 T helper cells orchestrate autoantibody production by supporting the proliferation and maturation of autoreactive B cells within ectopic tertiary lymphoid tissue. Conversely, autoantibody-mediated graft damage can trigger alloimmunity and the development of donor-specific HLA antibodies that can act in synergy to promote allograft rejection. Identification of the immunologic phenotypes of transplant recipients at risk of non-HLA antibody-mediated rejection, and the development of targeted therapies to treat such rejection, are sorely needed to improve both graft and patient survival.
Topics: Autoantibodies; Autoantigens; Collagen; Heparan Sulfate Proteoglycans; Humans; Kidney Transplantation; Receptor, Angiotensin, Type 1; Transplantation Immunology
PubMed: 27345243
DOI: 10.1038/nrneph.2016.88 -
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 -
Asian Journal of Transfusion Science 2020Alloimmunization is an immune response against foreign antigens which introduced into the body through transfusion, pregnancy, or transplantation. This phenomenon is a... (Review)
Review
BACKGROUND
Alloimmunization is an immune response against foreign antigens which introduced into the body through transfusion, pregnancy, or transplantation. This phenomenon is a big challenge in patients, which require regular transfusions. In the current study, we tried to have a comprehensive review on the status of alloimmunization in Iran. For this purpose, we searched for papers investigating alloimmunization in transfusion-dependent patients and also in patients with no regular transfusions who are candidate for surgery or who need blood.
METHODS
We searched PubMed, Google Scholar, SID, and MAGIRAN databases using the following keywords: "blood transfusion," "alloimmunization," "alloantibodies," "irregular antibodies," "red cell antibodies," and "Iran." No limitation for the date of publication and language of the papers was defined. All the identified records were then screened for the relevance and duplication.
RESULTS
A total of 22 papers were included in this study. All of the studies were conducted from 1999 to 2016 and providing alloimmunization data from different cities all over of Iran. In general, the results showed that the most prevalent alloantibodies are anti-Kell (anti-K antigen) and anti-Rh system, mainly anti-E, anti-D, anti-C, and anti-c.
CONCLUSION
Anti-Kell and anti-Rh antibodies are the most prevalent antibodies responsible for alloimmunization in Iranian population.
PubMed: 33162697
DOI: 10.4103/ajts.AJTS_137_17 -
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 -
Transfusion Medicine and Hemotherapy :... Oct 2018Antibodies to human neutrophil antigens (HNAs) have been implicated in transfusion-related acute lung injury and allo- and autoimmune neutropenia. To date, five HNA... (Review)
Review
BACKGROUND AND OBJECTIVE
Antibodies to human neutrophil antigens (HNAs) have been implicated in transfusion-related acute lung injury and allo- and autoimmune neutropenia. To date, five HNA systems are assigned, and during the last decades enormous efforts have been undertaken to identify the underlying genes and to characterize the antigens. This review of the literature will provide the current genetic, molecular and functional information on HNAs.
RECENT FINDINGS
New information on alleles and antigens has been added to nearly each of the five HNA systems. HNA-1d has been added as the antithetical epitope to HNA-1c that is located on the glycoprotein encoded by but not by and now are included as new alleles. A substitution was demonstrated as the main reason for the HNA-2-negative phenotype on neutrophils. The target glycoprotein of HNA-3 antibodies could be identified as choline transporter-like protein 2 (CTL2) encoded by The conformation sensitive epitope discriminates between arginine and glutamine at position 152 resulting in HNA-3a and HNA-3b. An additional Leu151Phe substitution can impair HNA-3a antibody binding. Recently an alloantibody against HNA-4b which discriminates from HNA-4a by an Arg61His exchange of the glycoprotein encoded by the gene was reported in neonatal alloimmune neutropenia. An update of the current HNA nomenclature based on the new findings was provided in 2016 by the ISBT Granulocyte Immunobiology Working Party nomenclature subcommittee.
CONCLUSIONS
The molecular basis of each of the five HNA antigen systems has been decoded during the past decades. This enables reliable molecular typing strategies, antibody detection and specification as well as development of new assays based on recombinant antigens. However, research on HNA alleles, antigens, and antibodies is not finally terminated and also in the future will add new findings.
PubMed: 30498408
DOI: 10.1159/000491031