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Cureus Aug 2023Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but fatal complication of blood transfusion that usually develops two to 30 days following a blood... (Review)
Review
Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but fatal complication of blood transfusion that usually develops two to 30 days following a blood transfusion giving rise to graft versus host disease (GVHD) clinical features that are consisting of fever, skin rash, jaundice, diarrhea, and pancytopenia. The disease is fulminant in most patients with a mortality rate of >90% of cases. The main aim of this review is to enhance awareness among medical practitioners about this fatal disease. Data were extracted manually from the main medical databases (Medline, Scopus, and Google Scholar) after the revision of selected articles and assessed for their contribution to the knowledge of TA-GVHD. TA-GVHD occurs when the viable donor T-cells in the blood or blood products attack the recipient's tissues which his/her immune system is incapable to destroy due to several reasons. The recipient's tissues that are usually involved in TA-GVHD include the liver, intestine, skin, lungs, and bone marrow. Any blood component either whole blood, packed red blood cells (RBCs), platelets, or fresh non-frozen plasma that contains viable T lymphocytes can cause TA-GVHD. Host immunodeficiency, transfusion of fresh blood, and partial human leukocyte antigen (HLA) matching between the donors and the recipients represent the major risk factors of TA-GVHD. Partial HLA matching includes immunocompetent recipients who receive blood from a first-degree relative also, seen in genetically homogenous populations because of high rates of consanguineous marriage. The diagnosis of TA-GVHD is mainly suspected based on clinical manifestations. However, a histopathological study of either skin or rectal biopsy is diagnostic. The treatment of TA-GVHD is generally not effective, unless the patient received emergency stem cell transplantation, while prevention via irradiation of blood or blood products represents the standard of care for this disease. In conclusion, medical practitioners should have a high index of suspicion for this disease. Moreover, future clinical trials targeting and comparing the outcomes of the different therapeutic options for TA-GVHD are required.
PubMed: 37753040
DOI: 10.7759/cureus.44148 -
Asian Journal of Transfusion Science 2023In many fields of clinical medicine and blood transfusion, the human leukocyte antigen (HLA) system is crucial. Alloimmunization happens as a result of an immune... (Review)
Review
In many fields of clinical medicine and blood transfusion, the human leukocyte antigen (HLA) system is crucial. Alloimmunization happens as a result of an immune response to foreign antigens encountered during blood transfusion. This gives rise to alloantibodies against red blood cells (RBCs), HLA, or human platelet antigen (HPA). HLA alloimmunization following allogeneic transfusion was shown to be a result of contaminating white blood cells (WBCs) present in the product. It is a common complication of transfusion therapy that leads to difficulties in clinical intolerance and refractoriness to platelet transfusion during patient management. Single-donor platelets, prophylactic HLA matching, leukoreduction, and irradiation of cellular blood products are some of the mechanisms to prevent HLA alloimmunization during a blood transfusion. Now, the best approach to reduce the occurrence of primary HLA alloimmunization is the removal of WBCs from the blood by filtration.
PubMed: 38274979
DOI: 10.4103/ajts.ajts_144_21 -
Haematologica Dec 2023Patients with severe aplastic anemia (SAA) are at high risk for morbidity and mortality due to severe infections. We aimed to characterize the role of granulocyte...
Patients with severe aplastic anemia (SAA) are at high risk for morbidity and mortality due to severe infections. We aimed to characterize the role of granulocyte transfusion (GT) in SAA. Primary outcomes were survival from first GT, including overall survival (OS) at last follow up, survival to discharge, and receipt of HSCT. Secondary outcomes included evaluation of clinical response at 7 and 30 days after GT initiation based on a clinical scoring system incorporating microbiological and radiographic response. Twenty-eight SAA patients underwent 30 GT courses with a per-dose median of 1.28 x 109 granulocyte cells/kilogram (range 0.45-4.52 x 109). OS from initial GT to median last follow up (551 days) was 50%, with 39% (11/28) alive at last follow up. Sixty-four percent (18/28) of all patients survived to hospital discharge. Patients with complete, partial, or stable response at 30 days had significantly improved OS compared to non-responders (p=0.0004). Eighty-six percent (18/21) of patients awaiting HSCT during GT underwent transplant and 62% (13/21) survived to post-HSCT discharge. Sex, type of infection, or percentage of days with absolute neutrophil count > 0.2x109/L during GT course were not predictive of survival (p=0.52, p=0.7, p=0.28). Nine of 28 (32%) patients developed new or increased human leukocyte antigen (HLA) alloimmunization during their GT course. GTs in SAA may impact survival in those with improvement or stabilization of their underlying infection. Alloimmunization can occur and OS in this population remains poor, but GTs may be a useful tool to bridge patients to curative treatment with HSCT.
PubMed: 38058170
DOI: 10.3324/haematol.2023.283826 -
Rheumatology (Oxford, England) Jan 2024Calprotectin (CLP) is a calcium-binding protein produced by neutrophils and monocytes in the course of inflammation. Today, the role of faecal CLP in chronic IBD is well... (Review)
Review
Calprotectin (CLP) is a calcium-binding protein produced by neutrophils and monocytes in the course of inflammation. Today, the role of faecal CLP in chronic IBD is well known, but in recent years attention has shifted towards circulating CLP. In fact, this molecule can be measured in different biological fluids: blood, saliva and urine, using different analytic methods that are described in this review. Furthermore, different data confirm the relevant role of serum CLP in autoimmune diseases. In this review we will highlight the correlation between high levels of circulating CLP and specific autoantibodies of major autoimmune pathologies paving the way to the employment of CLP measurement as useful biomarker for monitoring outcome in different pathologies.
Topics: Humans; Leukocyte L1 Antigen Complex; Inflammation; Biomarkers; Feces; Neutrophils; Inflammatory Bowel Diseases
PubMed: 37603715
DOI: 10.1093/rheumatology/kead405 -
Laboratory Investigation; a Journal of... Aug 2023In critically ill patients infected with SARS-CoV-2, early leukocyte recruitment to the respiratory system was found to be orchestrated by leukocyte trafficking...
In critically ill patients infected with SARS-CoV-2, early leukocyte recruitment to the respiratory system was found to be orchestrated by leukocyte trafficking molecules accompanied by massive secretion of proinflammatory cytokines and hypercoagulability. Our study aimed to explore the interplay between leukocyte activation and pulmonary endothelium in different disease stages of fatal COVID-19. Our study comprised 10 COVID-19 postmortem lung specimens and 20 control lung samples (5 acute respiratory distress syndrome, 2 viral pneumonia, 3 bacterial pneumonia, and 10 normal), which were stained for antigens representing the different steps of leukocyte migration: E-selectin, P-selectin, PSGL-1, ICAM1, VCAM1, and CD11b. Image analysis software QuPath was used for quantification of positive leukocytes (PSGL-1 and CD11b) and endothelium (E-selectin, P-selectin, ICAM1, VCAM1). Expression of IL-6 and IL-1β was quantified by RT-qPCR. Expression of P-selectin and PSGL-1 was strongly increased in the COVID-19 cohort compared with all control groups (COVID-19:Controls, 17:23, P < .0001; COVID-19:Controls, 2:75, P < .0001, respectively). Importantly, P-selectin was found in endothelial cells and associated with aggregates of activated platelets adherent to the endothelial surface in COVID-19 cases. In addition, PSGL-1 staining disclosed positive perivascular leukocyte cuffs, reflecting capillaritis. Moreover, CD11b showed a strongly increased positivity in COVID-19 compared with all controls (COVID-19:Controls, 2:89; P = .0002), indicating a proinflammatory immune microenvironment. Of note, CD11b exhibited distinct staining patterns at different stages of COVID-19 disease. Only in cases with very short disease course, high levels of IL-1β and IL-6 mRNA were observed in lung tissue. The striking upregulation of PSGL-1 and P-selectin reflects the activation of this receptor-ligand pair in COVID-19, increasing the efficiency of initial leukocyte recruitment, thus promoting tissue damage and immunothrombosis. Our results show that endothelial activation and unbalanced leukocyte migration play a central role in COVID-19 involving the P-selectin-PSGL-1 axis.
Topics: Humans; P-Selectin; Blood Platelets; Endothelial Cells; Interleukin-6; COVID-19; SARS-CoV-2; Leukocytes; Endothelium
PubMed: 37224922
DOI: 10.1016/j.labinv.2023.100179 -
Frontiers in Immunology 2023Immune checkpoint blockade is a compelling approach in tumor immunotherapy. Blocking inhibitory pathways in T cells has demonstrated clinical efficacy in different types... (Review)
Review
Immune checkpoint blockade is a compelling approach in tumor immunotherapy. Blocking inhibitory pathways in T cells has demonstrated clinical efficacy in different types of cancer and may hold potential to also stimulate innate immune responses. A novel emerging potential target for immune checkpoint therapy is leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1). LILRB1 belongs to the superfamily of leukocyte immunoglobulin-like receptors and exerts inhibitory functions. The receptor is expressed by a variety of immune cells including macrophages as well as certain cytotoxic lymphocytes and contributes to the regulation of different immune responses by interaction with classical as well as non-classical human leukocyte antigen (HLA) class I molecules. LILRB1 has gained increasing attention as it has been demonstrated to function as a phagocytosis checkpoint on macrophages by recognizing HLA class I, which represents a 'Don't Eat Me!' signal that impairs phagocytic uptake of cancer cells, similar to CD47. The specific blockade of the HLA class I:LILRB1 axis may provide an option to promote phagocytosis by macrophages and also to enhance cytotoxic functions of T cells and natural killer (NK) cells. Currently, LILRB1 specific antibodies are in different stages of pre-clinical and clinical development. In this review, we introduce LILRB1 and highlight the features that make this immune checkpoint a promising target for cancer immunotherapy.
Topics: Humans; Leukocyte Immunoglobulin-like Receptor B1; Neoplasms; Macrophages; Antineoplastic Agents; Histocompatibility Antigens Class I; Killer Cells, Natural; Immunoglobulins; Antigens, CD
PubMed: 37781391
DOI: 10.3389/fimmu.2023.1240275 -
Frontiers in Cellular and Infection... 2023The impact of COVID-19 on the world is still ongoing, and it is currently under regular management. Although most infected people have flu-like symptoms and can cure...
BACKGROUND
The impact of COVID-19 on the world is still ongoing, and it is currently under regular management. Although most infected people have flu-like symptoms and can cure themselves, coexisting pathogens in COVID-19 patients should not be taken lightly. The present study sought to investigate the coexisting pathogens in SARS-CoV-2 infected patients and identify the variety and abundance of dangerous microbes to guide treatment strategies with a better understanding of the untested factors.
METHODS
We extracted total DNA and RNA in COVID-19 patient specimens from nasopharyngeal swabs to construct a metagenomic library and utilize Next Generation Sequencing (NGS) to discover chief bacteria, fungi, and viruses in the body of patients. High-throughput sequencing data from Illumina Hiseq 4000 were analyzed using Krona taxonomic methodology for species diversity.
RESULTS
We studied 56 samples to detect SARS-CoV-2 and other pathogens and analyzed the species diversity and community composition of these samples after sequencing. Our results showed some threatening pathogens such as , , , and some previously reported pathogens. SARS-CoV-2 combined with bacterial infection is more common. The results of heat map analysis showed that the abundance of bacteria was mostly more than 1000 and that of viruses was generally less than 500. The pathogens most likely to cause SARS-CoV-2 coinfection or superinfection include , , , , and .
CONCLUSIONS
The current coinfection and superinfection status is not optimistic. Bacteria are the major threat group that increases the risk of complications and death in COVID-19 patients and attention should be paid to the use and control of antibiotics. Our study investigated the main types of respiratory pathogens prone to coexisting or superinfection in COVID-19 patients, which is valuable for identifying and treating SARS-CoV-2.
Topics: Humans; COVID-19; SARS-CoV-2; Coinfection; Superinfection; Viruses; Bacteria; Streptococcus pneumoniae; Klebsiella pneumoniae; Nasopharynx
PubMed: 37424777
DOI: 10.3389/fcimb.2023.1140548 -
Immunological platelet transfusion refractoriness: current insights from mechanisms to therapeutics.Platelets Dec 2024Although there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue... (Review)
Review
Although there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue that may lead to various severe adverse events. The burden of supplying platelets is worsened by rising market demand and limited donor pools of compatible platelets. Antibodies against platelet antigens are known to activate platelets through FcγR-dependent or complement-activated channels, thereby rapidly eliminating foreign platelets. Recently, other mechanisms of platelet clearance have been reported. The current treatment strategy for PTR is to select appropriate and compatible platelets; however, this necessitates a sizable donor pool and technical assistance for costly testing. Consolidation of these mechanisms should be of critical significance in providing insight to establish novel therapeutics to target immunological platelet refractoriness. Therefore, the purposes of this review were to explore the modulation of the immune system over the activation and elimination of allogeneic platelets and to summarize the development of alternative approaches for treating and avoiding alloimmunization to human leukocyte antigen or human platelet antigen in PTR.
Topics: Humans; Platelet Transfusion; Blood Platelets; Thrombocytopenia; Antigens, Human Platelet; HLA Antigens
PubMed: 38314765
DOI: 10.1080/09537104.2024.2306983 -
Haematologica Oct 2023β-thalassemia is an inherited anemia characterized by ineffective erythropoiesis. Blood transfusions are required for survival in transfusion-dependent β-thalassemia...
β-thalassemia is an inherited anemia characterized by ineffective erythropoiesis. Blood transfusions are required for survival in transfusion-dependent β-thalassemia and are also occasionally needed in patients with non-transfusion-dependent β-thalassemia. Patients with transfusion-dependent b-thalassemia often have elevated transferrin saturation (TSAT) and non-transferrin-bound iron (NTBI) levels, which can lead to organ iron overload, oxidative stress, and vascular damage. Vamifeport is an oral ferroportin inhibitor that was previously shown to ameliorate anemia, ineffective erythropoiesis, and dysregulated iron homeostasis in the Hbbth3/+ mouse model of β-thalassemia, under non-transfused conditions. Our study aimed to assess the effects of oral vamifeport on iron-related parameters (including plasma NTBI levels) and ineffective erythropoiesis following blood transfusions in Hbbth3/+ mice. A single dose of vamifeport prevented the transient transfusion-mediated NTBI increase in Hbbth3/+ mice. Compared with vehicle treatment, vamifeport significantly increased hemoglobin levels and red blood cell counts in transfused mice. Vamifeport treatment also significantly improved ineffective erythropoiesis in the spleens of Hbbth3/+ mice, with additive effects observed when treatment was combined with repeated transfusions. Vamifeport corrected leukocyte counts and significantly improved iron-related parameters (serum transferrin, TSAT and erythropoietin levels) versus vehicle treatment in Hbbth3/+ mice, irrespective of transfusion status. In summary, vamifeport prevented transfusion-mediated NTBI formation in Hbbth3/+ mice. When given alone or combined with blood transfusions, vamifeport also ameliorated anemia, ineffective erythropoiesis, and dysregulated iron homeostasis. Administering vamifeport together with repeated blood transfusions additively ameliorated anemia and ineffective erythropoiesis in this mouse model, providing preclinical proof-of-concept for the efficacy of combining vamifeport with blood transfusions in β-thalassemia.
Topics: Humans; Mice; Animals; beta-Thalassemia; Erythropoiesis; Iron; Thalassemia; Transferrin; Iron Overload; Blood Transfusion
PubMed: 37165842
DOI: 10.3324/haematol.2022.282328 -
Platelets Dec 2023Platelet transfusion refractoriness (PTR) is an intractable issue in hematological patients, which increases bleeding risks and hospitalization costs to a great extent.... (Review)
Review
Exploration of risk factors of platelet transfusion refractoriness and its impact on the prognosis of hematopoietic stem cell transplantation: a retrospective study of patients with hematological diseases.
Platelet transfusion refractoriness (PTR) is an intractable issue in hematological patients, which increases bleeding risks and hospitalization costs to a great extent. We reviewed 108 patients with hematological diseases including acute leukemia, myelodysplastic syndrome, aplastic anemia, and others who received allogeneic hematopoietic stem cell transplantation (HSCT) from January 2019 through December 2020. After multivariable logistic regression, we found that splenomegaly (odds ratio [OR] = 26.98, < .001) and JAK mutation (OR = 17.32, = .024) were independent risk factors for PTR. During the period of transplantation, patients in the PTR group had a significantly higher platelet transfusion demand, which was reflected in the increased number of platelet transfusions (10.23 ± 6.696 vs. 5.06 ± 1.904, < .001). After multivariate adjustment, PTR turned out to be independently associated with worse overall survival (hazard ratio = 2.794, 95% confidence interval = 1.083-7.207, = .034). In conclusion, we found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases. A history of PTR prior to allo-HSCT indicates a poor prognosis.
Topics: Humans; Retrospective Studies; Platelet Transfusion; Splenomegaly; Hematopoietic Stem Cell Transplantation; Prognosis; Myelodysplastic Syndromes; Risk Factors
PubMed: 37409458
DOI: 10.1080/09537104.2023.2229905