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Blood Nov 2021
Topics: CD36 Antigens; Humans; Thrombocytopenia, Neonatal Alloimmune
PubMed: 34735001
DOI: 10.1182/blood.2021012454 -
Transplant International : Official... Jan 2020Chronic lung allograft dysfunction (CLAD) comprises both bronchiolitis obliterans syndrome and restrictive allograft syndrome as subtypes. After lung transplantation,... (Review)
Review
Chronic lung allograft dysfunction (CLAD) comprises both bronchiolitis obliterans syndrome and restrictive allograft syndrome as subtypes. After lung transplantation, CLAD remains a major limitation for long-term survival, and lung transplant recipients therefore have poorer outcomes compared with recipients of other solid organ transplants. Although the number of lung transplants continues to increase globally, the field demands detailed understanding of immunoregulatory mechanisms and more effective individualized therapies to combat CLAD. Emerging evidence suggests that CLAD is multifactorial and involves a complex, delicate interplay of multiple factors, including perioperative donor characteristics, inflammation induced immediately following transplant, post-transplant infection and interplay between allo- and autoimmunity directed to donor antigens. Recently, identification of stress-induced exosome release from the transplanted organ has emerged as an underlying mechanism in the development of chronic rejection and promises to prompt novel strategies for future therapeutic interventions. In this review, we will discuss recent studies and ongoing research into the mechanisms for the development of CLAD, with emphasis on immune responses to lung-associated self-antigens-that is, autoimmunity.
Topics: Autoantibodies; Autoimmunity; Bronchiolitis Obliterans; Graft Rejection; Humans; Lung; Lung Transplantation
PubMed: 31393646
DOI: 10.1111/tri.13487 -
Experimental Eye Research May 2022Despite constant exposure to various environmental stimuli, the ocular surface remains intact and uninflamed while maintaining the transparency of the cornea and its... (Review)
Review
Despite constant exposure to various environmental stimuli, the ocular surface remains intact and uninflamed while maintaining the transparency of the cornea and its visual function. This 'immune privilege' of the ocular surface is not simply a result of the physical barrier function of the mucosal lining but, more importantly, is actively maintained through a variety of immunoregulatory mechanisms that prevent the disruption of immune homeostasis. In this review, we focus on essential molecular and cellular players that promote immune quiescence in steady-state conditions and suppress inflammation in disease-states. Specifically, we examine the interactions between the ocular surface and its local draining lymphoid compartment, by encompassing the corneal epithelium, corneal nerves and cornea-resident myeloid cells, conjunctival goblet cells, and regulatory T cells (Treg) in the context of ocular surface autoimmune inflammation (dry eye disease) and alloimmunity (corneal transplantation). A better understanding of the immunoregulatory mechanisms will facilitate the development of novel, targeted immunomodulatory strategies for a broad range of ocular surface inflammatory disorders.
Topics: Conjunctiva; Cornea; Corneal Transplantation; Dry Eye Syndromes; Humans; Inflammation
PubMed: 35257715
DOI: 10.1016/j.exer.2022.109007 -
Blood Nov 2022
Topics: Humans; Pregnancy; Female; Mice; Animals; Thrombocytopenia, Neonatal Alloimmune; Fetus; Prenatal Care; Integrin beta3
PubMed: 36394907
DOI: 10.1182/blood.2022017937 -
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 -
Trends in Immunology Jun 2022Despite an ever-increasing appreciation of how protein-coding genes shape immune responses, the molecular underpinnings of immune regulation remain incompletely... (Review)
Review
Despite an ever-increasing appreciation of how protein-coding genes shape immune responses, the molecular underpinnings of immune regulation remain incompletely understood. This incomplete picture impedes the development of more precise therapeutics and diagnostics for immune-mediated diseases. Long noncoding RNAs (lncRNAs) are versatile cell- and context-specific regulators of gene expression and cellular function. The number of lncRNA genes rivals that of protein-coding genes; however, comparatively little is known about their function. Even though the functions of most lncRNA genes are unknown, multiple lncRNAs have recently emerged as important immune regulators. Therefore, further unlocking the role of lncRNAs in the mammalian immune system coupled with their tissue-specific expression might lead to more precise therapeutics and diagnostics for immune disorders in general.
Topics: Animals; Gene Expression Regulation; Humans; Immune System; Immune System Diseases; Mammals; RNA, Long Noncoding
PubMed: 35501219
DOI: 10.1016/j.it.2022.04.002 -
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 -
Transplant International : Official... 2022Different types of kidney transplantations are performed worldwide, including biologically diverse donor/recipient combinations, which entail distinct patient/graft...
Different types of kidney transplantations are performed worldwide, including biologically diverse donor/recipient combinations, which entail distinct patient/graft outcomes. Thus, proper immunological and non-immunological risk stratification should be considered, especially for patients included in interventional randomized clinical trials. This paper was prepared by a working group within the European Society for Organ Transplantation, which submitted a Broad Scientific Advice request to the European Medicines Agency (EMA) relating to clinical trial endpoints in kidney transplantation. After collaborative interactions, the EMA sent its final response in December 2020, highlighting the following: 1) transplantations performed between human leukocyte antigen (HLA)-identical donors and recipients carry significantly lower immunological risk than those from HLA-mismatched donors; 2) for the same allogeneic molecular HLA mismatch load, kidney grafts from living donors carry significantly lower immunological risk because they are better preserved and therefore less immunogenic than grafts from deceased donors; 3) single-antigen bead testing is the gold standard to establish the repertoire of serological sensitization and is used to define the presence of a recipient's circulating donor-specific antibodies (HLA-DSA); 4) molecular HLA mismatch analysis should help to further improve organ allocation compatibility and stratify immunological risk for primary alloimmune activation, but without consensus regarding which algorithm and cut-off to use it is difficult to integrate information into clinical practice/study design; 5) further clinical validation of other immune assays, such as those measuring anti-donor cellular memory (T/B cell ELISpot assays) and non-HLA-DSA, is needed; 6) routine clinical tests that reliably measure innate immune alloreactivity are lacking.
Topics: Graft Rejection; Graft Survival; HLA Antigens; Histocompatibility Testing; Humans; Kidney Transplantation; Living Donors; Risk Assessment; Tissue Donors
PubMed: 35669972
DOI: 10.3389/ti.2022.10138 -
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