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Frontiers in Immunology 2023Antibody-mediated rejection is the leading cause of kidney graft dysfunction. The process of diagnosing it requires the performance of an invasive biopsy and subsequent... (Review)
Review
Antibody-mediated rejection is the leading cause of kidney graft dysfunction. The process of diagnosing it requires the performance of an invasive biopsy and subsequent histological examination. Early and sensitive biomarkers of graft damage and alloimmunity are needed to identify graft injury and eventually limit the need for a kidney biopsy. Moreover, other scenarios such as delayed graft function or interstitial fibrosis and tubular atrophy face the same problem. In recent years, interest has grown around extracellular vesicles, specifically exosomes actively secreted by immune cells, which are intercellular communicators and have shown biological significance. This review presents their potential as biomarkers in kidney transplantation and alloimmunity.
Topics: Kidney Transplantation; Extracellular Vesicles; Kidney; Exosomes; Biomarkers
PubMed: 37662919
DOI: 10.3389/fimmu.2023.1154650 -
Transfusion Medicine Reviews Oct 2020Refractoriness to platelet transfusion is a common clinical problem encountered by the transfusion medicine specialist. It is well recognized that most causes of... (Review)
Review
Refractoriness to platelet transfusion is a common clinical problem encountered by the transfusion medicine specialist. It is well recognized that most causes of refractoriness to platelet transfusion are not a consequence of alloimmunization to human leukocyte, platelet-specific, or ABO antigens, but are a consequence of platelet sequestration and consumption. This review summarizes the clinical factors that result in platelet refractoriness and highlights recent data describing novel biological mechanisms that contribute to this clinical problem.
Topics: Blood Platelets; Humans; Platelet Count; Platelet Transfusion; Spleen; Splenomegaly; Thrombocytopenia; Treatment Failure
PubMed: 33129606
DOI: 10.1016/j.tmrv.2020.09.002 -
Asian Journal of Transfusion Science 2023One of the complications of chronic transfusions in thalassemia is the development of red cell alloimmunization.
Red cell alloimmunization and associated risk factors in multiply transfused thalassemia patients: A prospective cohort study conducted at a tertiary care center in Northern India.
BACKGROUND
One of the complications of chronic transfusions in thalassemia is the development of red cell alloimmunization.
AIMS
The aim of the study was to determine the frequency, specificity of red cell alloantibodies, and factors influencing alloimmunization in multiply transfused thalassemia patients.
MATERIALS AND METHODS
The study was carried out prospectively on beta-thalassemia patients over 10 months. Plasma samples were used for antibody screening and identification using the column agglutination technique. Patients' clinical, laboratory, and transfusion details were obtained from hospital information system and patient files.
STATISTICAL ANALYSIS
Continuous variables were reported as median and quartile, whereas categorical variables were provided as numbers and proportions. < 0.05 was considered statistically significant.
RESULTS
Out of 255 patients, 17 (6.6%) patients developed alloantibodies. Alloimmunized patients had significantly higher median ages at their first transfusions (1 year vs. 0.5 years; = 0.042) than nonalloimmunized patients. Alloimmunized patients had significantly higher conjugated bilirubin ( = 0.016) and serum ferritin ( = 0.007). The majority of alloantibodies had specificity toward K antigen, followed by E, C, D, JKa, and JKb antigens. Alloimmunized patients received more units per year than nonalloimmunized patients (median, 30 vs. 24 units; < 0.001). The average transfusion interval time between two successive transfusions showed a significant difference ( < 0.001).
CONCLUSIONS
The prevalence of alloimmunization in thalassemia patients in North India is relatively low. Since most of the alloantibodies belong to Rh and Kell blood group system, extended phenotype-matched blood for Rh and Kell will be helpful in further preventing or decreasing the development of alloantibodies in multiply transfused thalassemia patients.
PubMed: 38274964
DOI: 10.4103/ajts.ajts_2_23 -
International Journal of Epidemiology Aug 2014Although the risks of adverse pregnancy outcomes associated with anti-D antibodies are well-recognized, much less is known concerning alloimmunization with other red...
BACKGROUND
Although the risks of adverse pregnancy outcomes associated with anti-D antibodies are well-recognized, much less is known concerning alloimmunization with other red blood cell antibodies detected during routine maternal screening. To date, most reports of adverse pregnancy outcomes associated with non-anti-D antibodies have been from small case studies. The aim of this study was to examine the associations of maternal alloimmunization with specific red blood cell antibodies and the risks of preterm birth and stillbirth in the Swedish population.
METHODS
All antibody screening, outcome and covariate data were obtained through linkages of Swedish national health and data registers. Follow-up in these population-based registers was available up to 31 December 2002. The final study sample consisted of 1,022,569 singleton births from 668,952 mothers during 1987-2002.
RESULTS
In total, 1.3% of the 1,022,569 study pregnancies were alloimmunized. In adjusted logistic regression models, compared with having no antibodies, alloimmunization with anti-D, anti-E, anti-C and anti-c was associated with increased risk of both stillbirth and preterm birth. In addition, anti-Kell was associated with increased risk of preterm birth and anti-Lea with increased risk of stillbirth. Compared with firstborn children, risk of preterm birth associated with alloimmunization was greater in subsequent births
CONCLUSIONS
In the largest study to date, alloimmunization with Rhesus, K- and -Lea red blood cell antibodies increased the risk of preterm birth and/or stillbirth. The association of anti-Lea with stillbirth was an unexpected finding. Further study of the consequences of non-anti-D alloimmunization is warranted.
Topics: Adult; Blood Group Incompatibility; Erythrocytes; Female; Humans; Isoantibodies; Logistic Models; Male; Membrane Glycoproteins; Metalloendopeptidases; Pregnancy; Premature Birth; Rh Isoimmunization; Rho(D) Immune Globulin; Stillbirth; Sweden; Young Adult
PubMed: 24801308
DOI: 10.1093/ije/dyu079 -
Frontiers in Immunology 2022Allograft rejection remains the major hurdle in lung transplantation despite modern immunosuppressive treatment. As part of the alloreactive process, B cells are... (Review)
Review
Allograft rejection remains the major hurdle in lung transplantation despite modern immunosuppressive treatment. As part of the alloreactive process, B cells are increasingly recognized as modulators of alloimmunity and initiators of a donor-specific humoral response. In chronically rejected lung allografts, B cells contribute to the formation of tertiary lymphoid structures and promote local alloimmune responses. However, B cells are functionally heterogeneous and some B cell subsets may promote alloimmune tolerance. In this review, we describe the current understanding of B-cell-dependent mechanisms in pulmonary allograft rejection and highlight promising future strategies that employ B cell-targeted therapies.
Topics: B-Lymphocytes; Graft Rejection; Humans; Lung; Lung Diseases; Lung Transplantation; Transplantation, Homologous
PubMed: 35320934
DOI: 10.3389/fimmu.2022.845867 -
Current Opinion in Organ Transplantation Feb 2010We provide evidence for the role of de-novo development of immune responses to self-antigens in the posttransplant period and its possible induction by alloimmunity in... (Review)
Review
PURPOSE OF REVIEW
We provide evidence for the role of de-novo development of immune responses to self-antigens in the posttransplant period and its possible induction by alloimmunity in the pathogenesis of chronic rejection following lung, heart and kidney transplantation. The present review details recent findings for the two distinct yet interdependent immune processes in the immunopathogenesis of chronic rejection.
RECENT FINDINGS
The contribution of both humoral and cell-mediated alloimmune responses against mismatched donor histocompatibility antigens (HLA) in the pathogenesis of chronic rejection is well established. Recent studies have focused on development of immune responses to self-antigens during the posttransplant period and its correlation with chronic rejection. These self-antigens include myosin and vimentin in cardiac, K-alpha-1-tubulin and collagen-V in lung and angiotensin II type 1 receptor, collagen-IV and VI in kidney transplants. During the posttransplant period, the development of immune responses to self-antigens is facilitated by induction of a distinct subset of autoreactive T-helper cells referred to as Th17 cells.
SUMMARY
Following organ transplantation, tissue injury and remodeling inflicted by antibodies (Abs) to HLA antigens is conducive to develop autoimmunity. Abs to HLA and self-antigens are detectable in the serum of transplant recipients who develop chronic rejection. Anti-HLA Abs are often present transiently but precede the development of Abs to self-antigens.
Topics: Animals; Autoantibodies; Autoantigens; Autoimmunity; Chronic Disease; Graft Rejection; Graft Survival; HLA Antigens; Humans; Immunity, Cellular; Immunity, Humoral; Isoantibodies; Organ Transplantation; Transplantation Tolerance; Treatment Outcome
PubMed: 19898237
DOI: 10.1097/MOT.0b013e3283342780 -
American Journal of Transplantation :... Jun 2009Chronic allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is the major cause of morbidity and mortality in human lung transplant recipients.... (Review)
Review
Chronic allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is the major cause of morbidity and mortality in human lung transplant recipients. While alloimmunity has a definite role, there is increasing interest in overall allograft injury and subsequent inflammation and remodeling. This review deals with nonalloimmune factors that may potentiate alloimmune injury. We discuss infection and reflux/aspiration as examples of allograft injury, which may lead to chronic loss of graft function and BOS. Surgical and nonsurgical treatments aimed at preventing these insults and improving survival are considered. The need for further evidence, including randomized-controlled trials, to evaluate the role of medical and surgical therapies is emphasized by the current literature.
Topics: Azithromycin; Bronchiolitis Obliterans; Gastroesophageal Reflux; Gram-Negative Bacterial Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lung Diseases; Lung Transplantation; Pneumonia; Pneumonia, Aspiration; Transplantation, Homologous
PubMed: 19459806
DOI: 10.1111/j.1600-6143.2009.02648.x -
Transplant International : Official... Aug 2019Late antibody-mediated rejection (ABMR) is a cardinal cause of kidney allograft failure, manifesting as a continuous and, in contrast with early rejection, often... (Review)
Review
Late antibody-mediated rejection (ABMR) is a cardinal cause of kidney allograft failure, manifesting as a continuous and, in contrast with early rejection, often clinically silent alloimmune process. While significant progress has been made towards an improved understanding of its molecular mechanisms and the definition of diagnostic criteria, there is still no approved effective treatment. In recent small randomized controlled trials, therapeutic strategies with promising results in observational studies, such as proteasome inhibitor bortezomib, anti-C5 antibody eculizumab, or high dose intravenous immunoglobulin plus rituximab, had no significant impact in late and/or chronic ABMR. Such disappointing results reinforce a need of new innovative treatment strategies. Potential candidates may be the interference with interleukin-6 to modulate B cell alloimmunity, or innovative compounds that specifically target antibody-producing plasma cells, such as antibodies against CD38. Given the phenotypic heterogeneity of ABMR, the design of adequate systematic trials to assess the safety and efficiency of such therapies, however, is challenging. Several trials are currently being conducted, and new developments will hopefully provide us with effective ways to counteract the deleterious impact of antibody-mediated graft injury. Meanwhile, the weight of evidence would suggest that, when approaching using existing treatments for established antibody-mediated rejection, "less may be more".
Topics: Allografts; Animals; Antibodies, Monoclonal, Humanized; Bortezomib; Graft Rejection; Graft Survival; Histocompatibility; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Isoantibodies; Kidney Transplantation; Proteasome Inhibitors; Randomized Controlled Trials as Topic; Rituximab; Transplantation, Homologous
PubMed: 30955215
DOI: 10.1111/tri.13436 -
Journal of Clinical Laboratory Analysis Jul 2021Platelet transfusion refractoriness (PTR) remains a difficult problem in patients requiring long-term platelet supportive care. However, there are little data on the...
BACKGROUND
Platelet transfusion refractoriness (PTR) remains a difficult problem in patients requiring long-term platelet supportive care. However, there are little data on the frequency of platelet antibodies in multiply transfused Chinese patients. Moreover, the relationship between peripheral regulatory T cells (Tregs) and PTR remains unclear.
METHODS
We retrospectively studied the frequency of alloimmunization against platelet antigens in patients receiving multiple transfusions between 2013 and 2017. Monoclonal antibody solid-phase platelet antibody test (MASPAT) kits were used to screen for platelet antibodies before each platelet transfusion. Peripheral Tregs and CD4 CD25 CD127 T cells were detected by flow cytometry, while transforming growth factor-beta (TGF-β) and interleukin (IL)-17 cytokines were detected by enzyme-linked immunosorbent assay.
RESULTS
A total of 399 patients who met the inclusion criteria were enrolled for the analysis of platelet antibodies and refractoriness. Among these patients, 10 (2.5%) were positive for platelet antibodies before transfusion and 47 (11.8%) became antibody-positive during the study period. The number of alloimmunized patients was significantly higher in patients with hematological disease as compared with other disease groups (p < 0.05). Refractoriness and alloimmunization occurred in 77 (19.3%) and 22 (28.6%) patients, respectively. There were no significant differences in CD4 , CD8 , and CD4 CD25 CD127 T cell numbers and plasma levels of TGF-β1 and IL-17 between patients with PTR and the control group.
CONCLUSIONS
Refractoriness was common in patients undergoing multiple platelet transfusions (19.3%), with alloimmunization observed in 28.6% of patients. However, Tregs in peripheral blood may not play a key role in PTR.
Topics: Adolescent; Adult; Aged; Antibodies; Cytokines; Female; Humans; Immunization; Lymphocyte Subsets; Male; Middle Aged; Platelet Transfusion; T-Lymphocytes, Regulatory; Young Adult
PubMed: 34125970
DOI: 10.1002/jcla.23864 -
Transfusion Medicine Reviews Oct 2020Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially serious bleeding condition in the fetus/newborn. FNAIT is usually considered as the... (Review)
Review
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially serious bleeding condition in the fetus/newborn. FNAIT is usually considered as the platelet counterpart of hemolytic disease of the fetus and newborn. In FNAIT, maternal alloantibodies against paternally inherited platelet antigens traverse the placenta and cause thrombocytopenia in the fetus/newborn. The most common and most serious cases of FNAIT among white people are caused by alloantibodies against the human platelet antigen 1a (HPA-1a), which is absent in 2.3% of women. Today, there is no screening for FNAIT, and for this reason, FNAIT is not suspected until an otherwise healthy child, born at term, presents with thrombocytopenia. Clinical management of subsequent pregnancies at risk of FNAIT is mostly based on the obstetric history. During the last 5 decades, hemolytic disease of the fetus and newborn caused by antibodies against RhD has successfully been prevented by administration of hyperimmune anti-D IgG drug products to RhD-negative women after delivery of an RhD-positive child. Similarly, a hyperimmune anti-HPA-1a IgG (NAITgam) is under development for the prevention of HPA-1a immunization and FNAIT. If NAITgam becomes licensed for FNAIT prophylaxis and national health authorities decide to include FNAIT screening in their antenatal health care programs, it will be necessary to improve today's tools for assessing the risk of FNAIT. Although the primary risk factor for HPA-1a immunization is platelet type HPA-1bb, not all HPA-1a-negative women develop anti-HPA-1a. The women who are HLA-DRB3:01:01 negative (72%) only rarely develop anti-HPA-1a, and for those few who become HPA-1a immunized, it is quite rare to have a child with severe thrombocytopenia. Determination of fetal HPA-1 type is important because 15% of HPA-1a-negative women will carry an HPA-1a-negative fetus and therefore not be at risk of FNAIT. The severity of FNAIT seems to be associated with the level of anti-HPA-1a. Hence, in Norway, for example, an Ab threshold of 3 IU/mL is used to distinguish between low- and high-risk pregnancies. The current review will discuss to what extent these analyses, as well as determination of subtypes of anti-HPA-1a (anti-β3, anti-αIIbβ3, and anti-αvβ3) and Fc core fucosylation of anti-HPA-1a IgG, can be used as risk stratification tools.
Topics: Antigens, Human Platelet; Biomarkers; Female; HLA-DRB3 Chains; Humans; Infant, Newborn; Integrin beta3; Isoantibodies; Pregnancy; Prenatal Care; Risk Assessment; Thrombocytopenia, Neonatal Alloimmune
PubMed: 33039264
DOI: 10.1016/j.tmrv.2020.09.004