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  1. Article ; Online: Inverse Relationship Between Lipopolysaccharide Concentration and Monocyte and Dendritic Cells Inflammatory Response.

    Perros, Alexis J / Flower, Robert L / Dean, Melinda M

    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

    2020  Volume 40, Issue 7, Page(s) 349–356

    Abstract: Dendritic cells (DCs) and monocytes are key immunoregulatory cells that link the innate and adaptive immune response. However, understanding of human cell-specific responses to different doses of stimuli including lipopolysaccharide (LPS) is limited. ... ...

    Abstract Dendritic cells (DCs) and monocytes are key immunoregulatory cells that link the innate and adaptive immune response. However, understanding of human cell-specific responses to different doses of stimuli including lipopolysaccharide (LPS) is limited. This study investigated the monocyte and classical DC (cDC)-specific, as well as the overall inflammatory response after exposure to varying doses of LPS. Fresh peripheral whole blood (
    MeSH term(s) Cells, Cultured ; Cytokines/biosynthesis ; Cytokines/blood ; Cytokines/immunology ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dose-Response Relationship, Drug ; Humans ; Inflammation/immunology ; Lipopolysaccharides/pharmacology ; Monocytes/drug effects ; Monocytes/immunology
    Chemical Substances Cytokines ; Lipopolysaccharides
    Language English
    Publishing date 2020-05-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1226675-9
    ISSN 1557-7465 ; 1079-9907
    ISSN (online) 1557-7465
    ISSN 1079-9907
    DOI 10.1089/jir.2019.0244
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  2. Article ; Online: Intraoperative cell salvage: The impact on immune cell numbers.

    Roets, Michelle / Sturgess, David / Tran, Thu / Obeysekera, Maheshi / Perros, Alexis / Tung, John-Paul / Flower, Robert / van Zundert, Andre / Dean, Melinda

    PloS one

    2023  Volume 18, Issue 8, Page(s) e0289177

    Abstract: Background: Patient outcomes are influenced by many confounding factors peri-operatively, including the type of surgery, anaesthesia, transfusion, and immune competence. We have previously demonstrated (in-vitro) that compared to allogeneic blood ... ...

    Abstract Background: Patient outcomes are influenced by many confounding factors peri-operatively, including the type of surgery, anaesthesia, transfusion, and immune competence. We have previously demonstrated (in-vitro) that compared to allogeneic blood transfusion (ABT), intraoperative cell salvage (ICS) improves immune competence. The peri-operative immune response is complex. Altered or impaired immune responses may predispose patients to develop adverse outcomes (i.e., post-operative wound infection, pneumonia, urinary tract infection etc.) Surgical patients may develop infection, even without the confirmed presence of a definite microbiological pathogen. With all these factors in mind it is important to consider changes in immune cell numbers (and sub-populations) and functional capacity during peri-operative transfusion.
    Methods: In this TRIMICS-Cell (Transfusion Related Immune Modulation and Intraoperative Cell Salvage-Cell numbers) study (n = 17, October 2018-November 2019) we prioritized and analysed peri-operative changes in the number and proportions of immune cell populations and sub-populations (B cells (CD20+), NK (natural killer) cells (CD56+), monocytes (CD14+), T cells (total CD3+ and sub-populations: T helper cells (CD4+), cytotoxic T cells (CD8+), effector T cells (CD4+ CD127+), activated effector T cells (CD4+ CD25+ CD127+) and regulatory T cells (CD4+ CD25+ CD127-)), plasmacytoid dendritic cells (pDC; Lineage-, HLA-DR+, CD11c-, CD123+), classical dendritic cell (cDC) (Lineage-, HLA-DR+, CD11c+), and cDC activation (Lineage-, HLA-DR+, CD11c+), co-stimulatory/adhesion molecules and pDC (CD9+, CD38+, CD80+, CD83+, CD86+, CD123+). Firstly we analysed the whole cohort of study patients and secondly according to the relevant transfusion modality (i.e., three study groups: those who received no transfusion, received ICS only (ICS), or both ICS and allogeneic packed red blood cells (pRBC) (ICS&RBC)), during major orthopaedic surgery.
    Results: For the whole study cohort (all patients), changes in immune cell populations were significant: leucocytes and specifically neutrophils increased post-operatively, returning towards pre-operative numbers by 48h post-operatively (48h), and lymphocytes reduced post-operatively returning to pre-operative numbers by 48h. When considering transfusion modalities, there were no significant peri-operative changes in the no transfusion group for all immune cell populations studied (cell numbers and proportions (%)). Significant changes in cell population numbers (i.e., leucocytes, neutrophils and lymphocytes) were identified in both transfused groups (ICS and ICS&RBC). Considering all patients, changes in immune cell sub-populations (NK cells, monocytes, B cells, T cells and DCs) and functional characteristics (e.g., co-stimulation markers, adhesion, activation, and regulation) were significant peri-operatively and when considering transfusion modalities. Interestingly DC numbers and functional capacity were specifically altered following ICS compared to ICS&RBC and pDCs were relatively preserved post-operatively following ICS.
    Conclusion: A transient peri-operative alteration with recovery towards pre-operative numbers by 48h post-surgery was demonstrated for many immune cell populations and sub-populations throughout. Immune cell sub-populations and functional characteristics were similar peri-operatively in those who received no transfusion but changed significantly following ICS and ICS&RBC. Interesting changes that require future study are a post-operative monocyte increase in the ICS&RBC group, changes in cDC considering transfusion modalities, and possibly preserved pDC numbers post-operatively following ICS. Future studies to assess changes in immune cell sub-populations, especially during peri-operative transfusion, while considering post-operative adverse outcomes, is recommended.
    MeSH term(s) Humans ; Interleukin-3 Receptor alpha Subunit ; HLA-DR Antigens ; T-Lymphocytes, Regulatory ; Blood Transfusion ; Cell Count ; Dendritic Cells
    Chemical Substances Interleukin-3 Receptor alpha Subunit ; HLA-DR Antigens
    Language English
    Publishing date 2023-08-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0289177
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  3. Article ; Online: Soluble mediators in packed red blood cells augment lipopolysaccharide-induced monocyte interleukin-1β production.

    Chong, Fenny / Rooks, Kelly M / Flower, Robert L / Dean, Melinda M

    Vox sanguinis

    2020  Volume 115, Issue 7, Page(s) 562–569

    Abstract: Background and objectives: Soluble mediators in packed red-blood-cell (PRBC) units have been hypothesized as a mechanism associated with transfusion-related immune modulation. Soluble mediators including damage-associated molecular patterns (DAMPs) are ... ...

    Abstract Background and objectives: Soluble mediators in packed red-blood-cell (PRBC) units have been hypothesized as a mechanism associated with transfusion-related immune modulation. Soluble mediators including damage-associated molecular patterns (DAMPs) are known to activate inflammasomes. Inflammasome complexes maturate caspase-1 and interleukin (IL)-1β. We assessed whether PRBC supernatants (SN) modulated IL-1β driven inflammation and whether macrophage migration inhibitory factor (MIF) was a contributing factor.
    Materials and methods: Isolated monocytes were incubated with PRBC-SN in an in vitro transfusion model. Lipopolysaccharide (LPS) was added in parallel to model a bacterial infection. Separately, recombinant MIF was used in the model to assess its role in IL-1β driven inflammation. IL-1β and caspase-1 were quantified in the PRBC-SN and culture SN from the in vitro model.
    Results: PRBC-SN alone did not induce IL-1β production from monocytes. However, PRBC-SN alone increased caspase-1 production. LPS alone induced both IL-1β and caspase-1 production. PRBC-SN augmented LPS-driven IL-1β and caspase-1 production. Recombinant MIF did not modulate IL-1β production in our model.
    Conclusions: Soluble mediators in PRBC modulate monocyte IL-1β inflammation, which may be a contributing factor to adverse effects of transfusion associated with poor patient outcomes. While MIF was present in PRBC-SN, we found no evidence that MIF was responsible for IL-1β associated immune modulation.
    MeSH term(s) Caspase 1/metabolism ; Erythrocytes/drug effects ; Erythrocytes/metabolism ; Humans ; Inflammasomes/metabolism ; Interleukin-1beta/genetics ; Interleukin-1beta/metabolism ; Intramolecular Oxidoreductases/metabolism ; Lipopolysaccharides/pharmacology ; Macrophage Migration-Inhibitory Factors/metabolism ; Monocytes/metabolism
    Chemical Substances IL1B protein, human ; Inflammasomes ; Interleukin-1beta ; Lipopolysaccharides ; Macrophage Migration-Inhibitory Factors ; Caspase 1 (EC 3.4.22.36) ; Intramolecular Oxidoreductases (EC 5.3.-) ; MIF protein, human (EC 5.3.2.1)
    Language English
    Publishing date 2020-05-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 80313-3
    ISSN 1423-0410 ; 0042-9007
    ISSN (online) 1423-0410
    ISSN 0042-9007
    DOI 10.1111/vox.12915
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    Zs.A 74: Show issues Location:
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  4. Article ; Online: Human neutrophil antigen 3 genotype impacts neutrophil-mediated endothelial cell cytotoxicity in a two-event model of TRALI.

    Chiaretti, Sara / Burton, Mark / Hassel, Penny / Radenkovic, Filip / Devikashri, Nilam / Sultana, Annette J / Temple, Fergal T / Dean, Melinda M / Tung, John-Paul

    Blood transfusion = Trasfusione del sangue

    2022  Volume 20, Issue 6, Page(s) 465–474

    Abstract: Background: Antibodies against human neutrophil antigen (HNA)-3a are associated with severe cases of transfusion-related acute lung injury (TRALI). The HNA-3 system is located on choline transporter-like 2 (CTL-2) protein. CTL-2 is encoded by the gene ... ...

    Abstract Background: Antibodies against human neutrophil antigen (HNA)-3a are associated with severe cases of transfusion-related acute lung injury (TRALI). The HNA-3 system is located on choline transporter-like 2 (CTL-2) protein. CTL-2 is encoded by the gene SLC44A2 and a single-nucleotide polymorphism c.461G>A results in two antigens: HNA-3a and HNA-3b. Three HNA-3 genotypes/ phenotypes exist: HNA-3aa, HNA-3bb, and HNA-3ab. Two different pathways of anti-HNA-3a TRALI have been described: a two-hit neutrophil-dependent pathway and a one-hit neutrophil-independent pathway. However, it is not clear whether HNA-3ab heterozygous patients have a lower risk of anti-HNA-3a-mediated TRALI compared to HNA-3aa homozygous patients.
    Materials and methods: Healthy volunteers were genotyped for HNA-3 by real-time polymerase chain reaction, and phenotyped for HNA-3a by granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT) against two donor sera containing anti-HNA-3a antibodies. The two sera were also used in in vitro models of human pulmonary microvascular endothelial cell (HLMVEC) cytotoxicity to investigate pathways of TRALI development.
    Results: For both anti-HNA-3a sera, GIFT results matched the genotype, with a lower GIFT ratio for HNA-3ab neutrophils compared to HNA-3aa neutrophils, whereas GAT results showed no difference in agglutination. HLMVEC cytotoxicity was not observed in a one-hit neutrophil-independent model but was observed in a two-hit neutrophil-dependent model. Differences in cytotoxicity were observed between the two anti-HNA-3a sera used. Consistent with reduced HNA-3a antigen density as measured by GIFT, HNA-3ab neutrophils mediated less HLMVEC cytotoxicity than HNA-3aa neutrophils.
    Conclusion: HNA-3 genotype and HNA-3a antigen expression impacted the severity of anti-HNA-3a-mediated HLMVEC cytotoxicity in a two-hit neutrophil-dependent model of TRALI. Different HNA-3a antibodies might also impact the magnitude of HLMVEC cytotoxicity.
    Language English
    Publishing date 2022-05-19
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2135732-8
    ISSN 2385-2070 ; 0041-1787 ; 1723-2007
    ISSN (online) 2385-2070
    ISSN 0041-1787 ; 1723-2007
    DOI 10.2450/2022.0013-22
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    Zs.A 798: Show issues Location:
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  5. Article ; Online: Transfusion-related acute lung injury (TRALI): Potential pathways of development, strategies for prevention and treatment, and future research directions.

    Tung, John-Paul / Chiaretti, Sara / Dean, Melinda M / Sultana, Annette J / Reade, Michael C / Fung, Yoke Lin

    Blood reviews

    2022  Volume 53, Page(s) 100926

    Abstract: Transfusion-related acute lung injury (TRALI) can occur during or after a transfusion, and remains a leading cause of transfusion-associated morbidity and mortality. TRALI is caused by the transfusion of either anti-leukocyte antibodies or biological ... ...

    Abstract Transfusion-related acute lung injury (TRALI) can occur during or after a transfusion, and remains a leading cause of transfusion-associated morbidity and mortality. TRALI is caused by the transfusion of either anti-leukocyte antibodies or biological response modifiers (BRMs). Experimental evidence suggests at least six different pathways that antibody-mediated TRALI might follow: (i) two hit neutrophil activation; (ii) monocyte and neutrophil dependent; (iii) endothelial cell, neutrophil Fc receptor, platelet and neutrophil extracellular trap dependent; (iv) direct monocyte activation; (v) direct endothelial cell activation; and (vi) endothelial cell, complement and monocyte dependent. Two of these pathways (i and v) also apply to BRM-mediated TRALI. Different antibodies or BRMs might initiate different pathways. Even though six pathways are described, these might not be distinct, and might instead be interlinked or proceed concurrently. The different pathways converge upon reactive oxygen species release which damages pulmonary endothelium, precipitating fluid leakage and the clinical symptoms of TRALI. Additional pathways to the six described are likely to also contribute to TRALI pathogenesis, and this requires further investigation. This review also discusses evidence of protective mechanisms and their implications for clinical TRALI treatment. Finally, it suggests directions for future research to support the translation of these findings into strategies to prevent and treat clinical TRALI.
    MeSH term(s) Antibodies ; Blood Transfusion ; Humans ; Immunologic Factors ; Neutrophil Activation ; Neutrophils ; Transfusion Reaction ; Transfusion-Related Acute Lung Injury/etiology ; Transfusion-Related Acute Lung Injury/prevention & control
    Chemical Substances Antibodies ; Immunologic Factors
    Language English
    Publishing date 2022-01-05
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 639015-8
    ISSN 1532-1681 ; 0268-960X
    ISSN (online) 1532-1681
    ISSN 0268-960X
    DOI 10.1016/j.blre.2021.100926
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  6. Article ; Online: Packed Red Blood Cell Transfusion Modulates Myeloid Dendritic Cell Activation and Inflammatory Response In Vitro.

    Ki, Katrina K / Faddy, Helen M / Flower, Robert L / Dean, Melinda M

    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

    2018  Volume 38, Issue 3, Page(s) 111–121

    Abstract: Transfusion of packed red blood cells (PRBCs) modulates patients' immune responses and clinical outcomes; however, the underpinning mechanism(s) remain unknown. The potential for PRBC to modulate myeloid dendritic cells (mDC) and blood DC antigen 3 was ... ...

    Abstract Transfusion of packed red blood cells (PRBCs) modulates patients' immune responses and clinical outcomes; however, the underpinning mechanism(s) remain unknown. The potential for PRBC to modulate myeloid dendritic cells (mDC) and blood DC antigen 3 was assessed using an in vitro transfusion model. In parallel, to model processes activated by viral or bacterial infection, toll-like receptor agonists polyinosinic:polycytidylic acid or lipopolysaccharide were added. Exposure to PRBC upregulated expression of CD83 and downregulated CD40 and CD80 on both DC subsets, and it suppressed production of interleukin (IL)-6, IL-8, IL-12, tumor necrosis factor-α, and interferon-gamma-inducible protein-10 by these cells. Similar effects were observed when modeling processes activated by concurrent infection. Furthermore, exposure to PRBC at date of expiry was associated with more pronounced effects in all assays. Our study suggests PRBC have an impact on recipient DC function, which may result in failure to establish an appropriate immune response, particularly in patients with underlying infection.
    MeSH term(s) Cytokines/blood ; Cytokines/immunology ; Dendritic Cells/immunology ; Erythrocyte Transfusion ; Erythrocytes/immunology ; Humans ; Inflammation/blood ; Inflammation/immunology
    Chemical Substances Cytokines
    Language English
    Publishing date 2018-03-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1226675-9
    ISSN 1557-7465 ; 1079-9907
    ISSN (online) 1557-7465
    ISSN 1079-9907
    DOI 10.1089/jir.2017.0099
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    Zs.A 1748: Show issues Location:
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  7. Article ; Online: Platelet concentrates modulate myeloid dendritic cell immune responses.

    Ki, Katrina K / Faddy, Helen M / Flower, Robert L / Dean, Melinda M

    Platelets

    2017  Volume 29, Issue 4, Page(s) 373–382

    Abstract: Platelet transfusion has been reported to modulate the recipients' immune system. To date, the precise mechanism(s) driving poor patient outcomes (e.g., increased rate of mortality, morbidity, infectious complications and prolonged hospital stays) ... ...

    Abstract Platelet transfusion has been reported to modulate the recipients' immune system. To date, the precise mechanism(s) driving poor patient outcomes (e.g., increased rate of mortality, morbidity, infectious complications and prolonged hospital stays) following platelet transfusion are largely undefined. To determine the potential for platelet concentrates (PC) to modulate responses of crucial immune regulatory cells, a human in vitro whole blood model of transfusion was established. Maturation and activation of human myeloid dendritic cells (mDC) and the specialized subset blood DC antigen (BDCA)3
    MeSH term(s) Blood Platelets/metabolism ; Dendritic Cells/immunology ; Humans ; Platelet Transfusion/methods
    Language English
    Publishing date 2017-05-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 1034283-7
    ISSN 1369-1635 ; 0953-7104
    ISSN (online) 1369-1635
    ISSN 0953-7104
    DOI 10.1080/09537104.2017.1306045
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    Zs.A 2888: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  8. Article ; Online: Understanding occult hepatitis C infection.

    An, Timothy / Dean, Melinda / Flower, Robert / Tatzenko, Tayla / Chan, Hiu Tat / Kiely, Philip / Faddy, Helen M

    Transfusion

    2020  Volume 60, Issue 9, Page(s) 2144–2152

    Abstract: Background: Occult hepatitis C infection (OCI) is a type of hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells (PBMCs) and the absence of HCV RNA in serum.: Study design and ... ...

    Abstract Background: Occult hepatitis C infection (OCI) is a type of hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells (PBMCs) and the absence of HCV RNA in serum.
    Study design and methods: A literature review was conducted to identify articles that characterized OCI as a disease, including its epidemiology, mode of transmission, pattern of infection, progression, and treatment.
    Results: OCI patients experience a milder degree of inflammatory and cirrhotic changes than patients with chronic hepatitis C. OCI is transmissible parenterally both in vivo and in vitro, however the duration and outcome of OCI remains unclear. OCI is most consistently found in patients with previous hepatitis C disease and hemodialysis patients. Beyond the at-risk populations, OCI has also been demonstrated among healthy individuals and blood donors.
    Conclusions: This review summarises our current understanding of OCI and suggests areas for further research to improve our understanding of this phenomenon, including a better understanding of its epidemiology and full clinical course. The current understanding of OCI and its clinical implications remain limited. Further standardized detection methods, ongoing surveillance, and investigation of its potential transmissions are required.
    MeSH term(s) Blood Donors ; Hepacivirus/metabolism ; Hepatitis C, Chronic/blood ; Hepatitis C, Chronic/pathology ; Hepatitis C, Chronic/therapy ; Hepatocytes/metabolism ; Hepatocytes/pathology ; Hepatocytes/virology ; Humans ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/pathology ; Leukocytes, Mononuclear/virology ; RNA, Viral/blood ; Renal Dialysis ; Risk Factors
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2020-08-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.16006
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    Zs.A 284: Show issues Location:
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  9. Article ; Online: Incorporation of fluorescein conjugated function-spacer-lipid constructs into the red blood cell membrane facilitates detection of labeled cells for the duration of ex-vivo storage.

    Ki, Katrina K / Flower, Robert L / Faddy, Helen M / Dean, Melinda M

    Journal of immunological methods

    2016  Volume 429, Page(s) 66–70

    Abstract: The contribution of ex-vivo storage duration of packed red blood cells (PRBC) to patient outcomes and transfusion-related immunomodulation (TRIM) remains a broadly debated area in transfusion medicine. Kode™ Technology with fluorescein conjugated ... ...

    Abstract The contribution of ex-vivo storage duration of packed red blood cells (PRBC) to patient outcomes and transfusion-related immunomodulation (TRIM) remains a broadly debated area in transfusion medicine. Kode™ Technology with fluorescein conjugated function-spacer-lipid (FSL-FLRO4) constructs is a tool that can aid in-vitro visualization and tracking of red blood cells (RBC) during routine storage. FSL-FLRO4 is incorporated into the RBC membrane without altering cell function. In this study, we explore the suitability of this technology to label clinical grade PRBC and to determine if the label would be retained during ex-vivo storage. Firstly, to confirm feasibility and assess the limit of detection of FSL-FLRO4 on PRBC at date of expiry (42 days post-collection), we tracked the binding of FSL-FLRO4 on PRBC at weekly intervals during routine storage. Over the time course, all cells remained labelled with FSL-FLRO4, although a decrease in the intensity of labelling was observed (P<0.0001). We then further investigated differences in FSL-FLRO4 labelling during RBC storage by labelling separated light-young and dense-old RBC from the same PRBC unit. There were no differences in the capacity of FSL-FLRO4 to label these different RBC subsets. Together, these data demonstrate that FSL-FLRO4 is a suitable reagent for labelling PRBC at any point during routine storage. This technology will facilitate the development of immunoassays and transfusion models focused on addressing the mechanisms involved in TRIM.
    MeSH term(s) Blood Preservation ; Cell Separation/methods ; Erythrocyte Membrane/chemistry ; Erythrocyte Membrane/immunology ; Erythrocyte Transfusion ; Fluorescein/analysis ; Fluorescein/chemistry ; Humans ; Immunoassay ; Lipids/chemistry ; Lipids/immunology ; Time Factors
    Chemical Substances Lipids ; Fluorescein (TPY09G7XIR)
    Language English
    Publishing date 2016-02
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120142-6
    ISSN 1872-7905 ; 0022-1759
    ISSN (online) 1872-7905
    ISSN 0022-1759
    DOI 10.1016/j.jim.2016.01.003
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    Zs.A 795: Show issues Location:
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  10. Article ; Online: Genetic Variants Within the Erythroid Transcription Factor, KLF1, and Reduction of the Expression of Lutheran and Other Blood Group Antigens: Review of the In(Lu) Phenotype.

    Fraser, Nicole S / Knauth, Christine M / Moussa, Assia / Dean, Melinda M / Hyland, Catherine A / Perkins, Andrew C / Flower, Robert L / Schoeman, Elizna M

    Transfusion medicine reviews

    2019  Volume 33, Issue 2, Page(s) 111–117

    Abstract: Erythroid-specific Krüppel-like factor 1, or KLF1, is an integral transcriptional activator for erythropoiesis. Genetic variants within KLF1 can result in a range of erythropoietic clinical phenotypes from benign to significant. The In(Lu) phenotype ... ...

    Abstract Erythroid-specific Krüppel-like factor 1, or KLF1, is an integral transcriptional activator for erythropoiesis. Genetic variants within KLF1 can result in a range of erythropoietic clinical phenotypes from benign to significant. The In(Lu) phenotype refers to changes in the quantitative expression of blood group-associated red cell surface molecules due to KLF1 variants which are otherwise clinically benign. These clinically benign KLF1 variants are associated with a reduced expression of 1 or more red cell membrane proteins/carbohydrates that carry blood group antigens for the LU (Lutheran), IN (Indian), P1PK, LW (Landsteiner-Wiener), KN (Knops), OK, RAPH, and I blood group systems. This is of significance during routine serologic blood typing when expression falls below the test sensitivity and therefore impacts on the ability to accurately detect the presence of affected blood group antigens. This is of clinical importance because the transfusion requirements for individuals with the In(Lu) phenotype differ from those of individuals that have a true Lu
    MeSH term(s) Blood Group Antigens/genetics ; Blood Transfusion ; Genotype ; Humans ; Kruppel-Like Transcription Factors/genetics ; Lutheran Blood-Group System/genetics ; Mutation ; Phenotype ; Polymorphism, Genetic ; Sequence Analysis, DNA
    Chemical Substances Blood Group Antigens ; Kruppel-Like Transcription Factors ; Lutheran Blood-Group System ; erythroid Kruppel-like factor
    Language English
    Publishing date 2019-02-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 639107-2
    ISSN 1532-9496 ; 0887-7963
    ISSN (online) 1532-9496
    ISSN 0887-7963
    DOI 10.1016/j.tmrv.2019.01.004
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