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Current Opinion in Organ Transplantation Oct 2023De novo HLA-DQ antibodies are the most frequently observed after solid-organ allotransplantation; and are associated with the worse adverse graft outcomes compared with... (Review)
Review
PURPOSE OF REVIEW
De novo HLA-DQ antibodies are the most frequently observed after solid-organ allotransplantation; and are associated with the worse adverse graft outcomes compared with all other HLA antibodies. However, the biological explanation for this observation is not yet known. Herein, we examine unique characteristics of alloimmunity directed specifically against HLA-DQ molecules.
RECENT FINDINGS
While investigators attempted to decipher functional properties of HLA class II antigens that may explain their immunogenicity and pathogenicity, most early studies focused on the more expressed molecule - HLA-DR. We here summarize up-to-date literature documenting specific features of HLA-DQ, as compared to other class II HLA antigens. Structural and cell-surface expression differences have been noted on various cell types. Some evidence suggests variations in antigen-presenting function and intracellular activation pathways after antigen/antibody interaction.
SUMMARY
The clinical effects of donor-recipient incompatibility at HLA-DQ, the risk of generating de novo antibodies leading to rejection, and the inferior graft outcomes indicate increased immunogenicity and pathogenicity that is unique to this HLA antigen. Clearly, knowledge generated for HLA-DR cannot be applied interchangeably. Deeper understanding of features unique to HLA-DQ may support the generation of targeted preventive-therapeutic strategies and ultimately improve solid-organ transplant outcomes.
Topics: Humans; Kidney Transplantation; Isoantibodies; HLA-DQ Antigens; Histocompatibility Testing; HLA-DR Antigens; Graft Rejection
PubMed: 37219535
DOI: 10.1097/MOT.0000000000001079 -
Revista Brasileira de Ginecologia E... 2024RhD alloimmunization in pregnancy is still the main cause of hemolytic disease of the fetus and neonate (HDFN). Nevertheless, there are other antigens that may be... (Review)
Review
RhD alloimmunization in pregnancy is still the main cause of hemolytic disease of the fetus and neonate (HDFN). Nevertheless, there are other antigens that may be associated with the occurrence of this phenomenon and that have been growing in proportion, given that current prevention strategies focus only on anti-RhD antibodies. Although not widespread, the screening and diagnostic management of the disease caused by these antibodies has recommendations in the literature. For this reason, the following review was carried out with the objective of listing the main red blood cell antigen groups described - such as Rh, ABO, Kell, MNS, Duffy, Kidd, among others - addressing the clinical importance of each one, prevalence in different countries, and recommended management when detecting such antibodies during pregnancy.
PubMed: 38765509
DOI: 10.61622/rbgo/2024AO22 -
Frontiers in Immunology 2021During pregnancy the formation of alloreactive anti-human leukocyte antigen (HLA) antibodies are a major cause of acute rejection in organ transplantation and of adverse...
During pregnancy the formation of alloreactive anti-human leukocyte antigen (HLA) antibodies are a major cause of acute rejection in organ transplantation and of adverse effects in blood transfusion. The purpose of the study was to identify maternal HLA class Ib genetic factors associated with anti-HLA allo-immunization in pregnancy and the degree of tolerance estimated by IgG4 expression. In total, 86 primiparous women with singleton pregnancies were included in the study. Maternal blood samples and umbilical cord samples were collected at delivery. Clinical data were obtained. Maternal blood serum was screened for HLA class I and II antibodies, identification of Donor Specific Antibody (DSA), activation of complement measured by C1q and IgG4 concentrations. Mothers were genotyped for HLA class Ib ( and ). Anti-HLA class I and II antibodies were identified in 24% of the women. The maternal allele was significantly associated with a higher fraction of anti-HLA I immunization (20.0% 4.8%, p = 0.048). The maternal HLA-G 3'-untranslated region haplotype and the allele were significantly associated with a low anti-HLA I C1q activation (16.7% . 57.1%, p = 0.028; 16.7% 50.0%, p = 0.046; respectively). Both and - showed significantly higher levels of IgG4 compared with the other haplotypes. The results support an association of certain alleles with allo-immunization during pregnancy. Further studies are needed to elucidate the roles of and in reducing the risk for allo-immunization.
Topics: Adolescent; Adult; Alleles; Female; Gene Dosage; Gene Frequency; Genetic Association Studies; Genotype; HLA-DQ Antigens; Humans; Immunization; Immunoglobulin G; Isoantibodies; Phenotype; Polymorphism, Genetic; Pregnancy; Young Adult
PubMed: 33859649
DOI: 10.3389/fimmu.2021.657217 -
Blood May 2020
Topics: Animals; Erythrocyte Transfusion; Erythrocytes; Glycoproteins; Inflammation; Mice; Poly I-C
PubMed: 32463889
DOI: 10.1182/blood.2020005971 -
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 -
International Journal of Molecular... Oct 2021The NOD, LRR, and pyrin domain-containing 3 (NLRP3) protein has been established as a central component of the inflammasome and regulates the inflammatory response to a... (Review)
Review
The NOD, LRR, and pyrin domain-containing 3 (NLRP3) protein has been established as a central component of the inflammasome and regulates the inflammatory response to a myriad of environmental, microbial, and endogenous danger stimuli. Assembly of the NLRP3 inflammasome results in the cleavage and activation of caspase-1, in turn causing release of the pro-inflammatory interleukins 1-beta and 18. This activation response, while crucial to coordinated innate immune defense, can be aberrantly activated by the likes of cell-free DNA, and cause significant autoimmune pathology. Complications of autoimmunity induced by aberrant NLRP3 inflammasome activation have a great degree of mechanistic crossover with alloimmune injury in solid organ transplant, and stratagems to neutralize NLRP3 inflammasome activation may prove beneficial in solid organ transplant management. This article reviews NLRP3 inflammasome biology and the pathology associated with its hyperactivation, as well as the connections between NLRP3 inflammasome activation and allograft homeostasis.
Topics: Animals; Autoimmunity; DNA; Humans; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Neutrophils; Organ Specificity; Organ Transplantation; Protein Processing, Post-Translational
PubMed: 34639062
DOI: 10.3390/ijms221910721 -
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 -
Clinics in Laboratory Medicine Mar 2021Red blood cell (RBC) transfusion is critical in managing acute and chronic complications of sickle cell disease. Alloimmunization and iron overload remain significant... (Review)
Review
Red blood cell (RBC) transfusion is critical in managing acute and chronic complications of sickle cell disease. Alloimmunization and iron overload remain significant complications of transfusion therapy and are minimized with prophylactic Rh and K antigen RBC matching and iron chelation. Matched sibling donor hematopoietic stem cell transplant (HSCT) is a curative therapeutic option. Autologous hematopoietic stem cell (HSC)-based gene therapy has recently shown great promise, for which obtaining sufficient HSCs is essential for success. This article discusses RBC transfusion indications and complications, transfusion support during HSCT, and HSC mobilization and collection for autologous HSCT with gene therapy.
Topics: Anemia, Sickle Cell; Blood Group Antigens; Blood Transfusion; Cell- and Tissue-Based Therapy; Erythrocyte Transfusion; Humans
PubMed: 33494879
DOI: 10.1016/j.cll.2020.10.007 -
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 -
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