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  1. Article ; Online: Virtual crossmatching for deceased donor transplantation: one size does not fit all.

    Pinelli, David F / Tambur, Anat R

    Kidney international

    2020  Volume 97, Issue 4, Page(s) 659–662

    MeSH term(s) Blood Grouping and Crossmatching ; Humans ; Tissue Donors
    Language English
    Publishing date 2020-03-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2020.02.001
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    Zs.A 797: Show issues Location:
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  2. Article ; Online: Understanding the impact of HLA molecular mismatch in solid organ transplantation: Are we there yet?

    Jackson, Annette M / Pinelli, David F

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2020  Volume 21, Issue 1, Page(s) 9–10

    MeSH term(s) Cohort Studies ; Histocompatibility ; Humans ; Organ Transplantation ; Tacrolimus ; United States
    Chemical Substances Tacrolimus (WM0HAQ4WNM)
    Language English
    Publishing date 2020-11-18
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.16376
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  3. Article ; Online: Novel insights into anti-CD40/CD154 immunotherapy in transplant tolerance.

    Pinelli, David F / Ford, Mandy L

    Immunotherapy

    2015  Volume 7, Issue 4, Page(s) 399–410

    Abstract: Since the discovery of the CD40-CD154 costimulatory pathway and its critical role in the adaptive immune response, there has been considerable interest in therapeutically targeting this interaction with monoclonal antibodies in transplantation. ... ...

    Abstract Since the discovery of the CD40-CD154 costimulatory pathway and its critical role in the adaptive immune response, there has been considerable interest in therapeutically targeting this interaction with monoclonal antibodies in transplantation. Unfortunately, initial promise in animal models gave way to disappointment in clinical trials following a number of thromboembolic complications. However, recent mechanistic studies have identified the mechanism of these adverse events, as well as detailed a myriad of interactions between CD40 and CD154 on a wide variety of immune cell types and the critical role of this pathway in generating both humoral and cell-mediated alloreactive responses. This has led to resurgence in interest and the potential resurrection of anti-CD154 and anti-CD40 antibodies as clinically viable therapeutic options.
    MeSH term(s) Animals ; Antibodies, Monoclonal/therapeutic use ; CD40 Antigens/immunology ; CD40 Antigens/metabolism ; CD40 Ligand/immunology ; CD40 Ligand/metabolism ; Clinical Trials as Topic ; Disease Models, Animal ; Graft Rejection/etiology ; Graft Rejection/prevention & control ; Humans ; Immunotherapy/methods ; Lymphocyte Activation/drug effects ; Organ Transplantation ; Receptor Cross-Talk/drug effects ; Receptors, Antigen, T-Cell/metabolism ; Signal Transduction/drug effects ; Transplantation Tolerance/drug effects
    Chemical Substances Antibodies, Monoclonal ; CD40 Antigens ; Receptors, Antigen, T-Cell ; CD40 Ligand (147205-72-9)
    Language English
    Publishing date 2015
    Publishing country England
    Document type Journal Article ; Review
    ISSN 1750-7448
    ISSN (online) 1750-7448
    DOI 10.2217/imt.15.1
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  4. Article ; Online: Memory T cell-mediated rejection is mitigated by FcγRIIB expression on CD8

    Morris, Anna B / Pinelli, David F / Liu, Danya / Wagener, Maylene / Ford, Mandy L

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2020  Volume 20, Issue 8, Page(s) 2206–2215

    Abstract: Donor-reactive memory T cells generated via heterologous immunity represent a potent barrier to long-term graft survival following transplantation because of their increased precursor frequency, rapid effector function, altered trafficking patterns, and ... ...

    Abstract Donor-reactive memory T cells generated via heterologous immunity represent a potent barrier to long-term graft survival following transplantation because of their increased precursor frequency, rapid effector function, altered trafficking patterns, and reduced reliance on costimulation signals for activation. Thus, the identification of pathways that control memory T cell survival and secondary recall potential may provide new opportunities for therapeutic intervention. Here, we discovered that donor-specific effector/memory CD8
    MeSH term(s) Animals ; CD8-Positive T-Lymphocytes ; Graft Rejection/etiology ; Graft Survival ; Humans ; Immunologic Memory ; Mice ; Mice, Inbred C57BL
    Keywords covid19
    Language English
    Publishing date 2020-03-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.15837
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  5. Article ; Online: Impact of SIRPα polymorphism on transplant outcomes in HLA-identical living donor kidney transplantation.

    Garcia-Sanchez, Cynthia / Casillas-Abundis, M Aurora / Pinelli, David F / Tambur, Anat R / Hod-Dvorai, Reut

    Clinical transplantation

    2021  Volume 35, Issue 9, Page(s) e14406

    Abstract: Signal-regulatory protein α (SIRPα), a polymorphic inhibitory membrane-bound receptor, and its ligand CD47 have recently been implicated in the modulation of innate immune allorecognition in murine models. Here, we investigate the potential impact of ... ...

    Abstract Signal-regulatory protein α (SIRPα), a polymorphic inhibitory membrane-bound receptor, and its ligand CD47 have recently been implicated in the modulation of innate immune allorecognition in murine models. Here, we investigate the potential impact of SIRPα donor-recipient mismatches on graft outcomes in human kidney transplantation. To eliminate the specific role of HLA-matching in alloresponse, we genotyped the two most common variants of SIRPα in a cohort of 55 HLA-identical, biologically-related, donor-recipient pairs. 69% of pairs were SIRPα identical. No significant differences were found between donor-recipient SIRPα-mismatch status and T cell-mediated rejection/borderline changes (25.8% vs. 25%) or slow graft function (15.8% vs. 17.6%). A trend towards more graft failure (GF) (23.5% vs. 5.3%, P = .06), interstitial inflammation (50% vs. 23%, P = .06) and significant changes in peritubular capillaritis (ptc) (25% vs. 0%, P = .02) were observed in the SIRPα-mismatched group. Unexpectedly, graft-versus-host (GVH) SIRPα-mismatched pairs exhibited higher rates of GF and tubulitis (38% vs. 5%, P = .031 and .61 ± .88 vs. 0, P = .019; respectively). Whether the higher prevalence of ptc in SIRPα-mismatched recipients and the higher rates of GF in GVH SIRPα-mismatched pairs represent a potential role for SIRPα in linking innate immunity and alloimmune rejection requires further investigation in larger cohorts.
    MeSH term(s) Animals ; Antigens, Differentiation/genetics ; Graft Rejection/epidemiology ; Graft Rejection/etiology ; Graft Survival ; HLA Antigens/genetics ; Hematopoietic Stem Cell Transplantation ; Histocompatibility ; Histocompatibility Testing ; Humans ; Kidney Transplantation ; Living Donors ; Mice ; Receptors, Immunologic/genetics
    Chemical Substances Antigens, Differentiation ; HLA Antigens ; Receptors, Immunologic ; SIRPA protein, human
    Language English
    Publishing date 2021-07-11
    Publishing country Denmark
    Document type Journal Article
    ZDB-ID 639001-8
    ISSN 1399-0012 ; 0902-0063
    ISSN (online) 1399-0012
    ISSN 0902-0063
    DOI 10.1111/ctr.14406
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    Zs.A 2204: Show issues Location:
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  6. Article: HLA Epitopes - Are We Ready for Clinical Prime Time? Historic Perspective and Future Needs.

    Dvorai, Reut H / Pinelli, David F / Tambur, Anat R

    Clinical transplants

    2016  Volume 32, Page(s) 63–71

    Abstract: A significant barrier to long-term transplant success is the development of de novo donor-specific human leukocyte antigen (HLA) antibodies. The best approach to minimize the risk of developing such antibodies is an HLA identical transplant, but the ... ...

    Abstract A significant barrier to long-term transplant success is the development of de novo donor-specific human leukocyte antigen (HLA) antibodies. The best approach to minimize the risk of developing such antibodies is an HLA identical transplant, but the likelihood of finding such an organ is very low. The alternative is to identify "permissible mismatches" - HLA antigen mismatches that are less likely to induce an immune response. In the past few years, it has become clear that matching at the "epitope level" is the likely solution; however, we are still struggling with how to define HLA epitopes. Herein, we provide a short review of the development of the epitope concept within the HLA field, with the hope that it sheds light on present knowledge. We follow with our personal opinion on where the future is leading us.
    MeSH term(s) Antibodies ; Epitopes ; HLA Antigens ; Histocompatibility Testing ; Humans ; Tissue Donors
    Chemical Substances Antibodies ; Epitopes ; HLA Antigens
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article
    ZDB-ID 607631-2
    ISSN 0890-9016
    ISSN 0890-9016
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  7. Article ; Online: Corrigendum to 'Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report' [American Journal of Transplantation 23 (2023) 133-149].

    Tambur, Anat R / Bestard, Oriol / Campbell, Patricia / Chong, Anita S / Crespo, Marta / Ford, Mandy L / Gebel, Howard M / Heidt, Sebastiaan / Hickey, Michelle / Jackson, Annette / Kosmoliaptsis, Vasilis / Lefaucheur, Carmen / Louis, Kevin / Mannon, Roslyn B / Mengel, Michael / Morris, Anna / Pinelli, David F / Reed, Elaine F / Schinstock, Carrie /
    Taupin, Jean-Luc / Valenzuela, Nicole / Wiebe, Chris / Nickerson, Peter

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2023  Volume 23, Issue 5, Page(s) 694

    Language English
    Publishing date 2023-03-13
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1016/j.ajt.2023.03.002
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  8. Article ; Online: The quest to decipher HLA immunogenicity: Telling friend from foe.

    Tambur, Anat R / McDowell, Hannah / Hod-Dvorai, Reut / Abundis, Maria A C / Pinelli, David F

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2019  Volume 19, Issue 10, Page(s) 2910–2925

    Abstract: Molecular mismatch load analysis was recently introduced as a means for performing risk stratification following organ transplantation. However, although good correlation was demonstrated between molecular mismatch load and generation of de novo donor- ... ...

    Abstract Molecular mismatch load analysis was recently introduced as a means for performing risk stratification following organ transplantation. However, although good correlation was demonstrated between molecular mismatch load and generation of de novo donor-specific HLA antibody (DSA), quite a few exceptions exist, and the underlying factors that define HLA immunogenicity remain unclear. Herein, we present a new paradigm to interrogate differences between molecular mismatches that lead to the generation of de novo DSA and those that do not (the 2MM1DSA cohort). Specifically, patients transplanted across 2 HLA-DQ mismatches, who formed de novo DSA only to one mismatch (foe) but not the other (friend), provide a unique environment in which patient-specific factors that affect the immune response other than immunogenicity, such as infection and immunosuppression, can be controlled for. It further permits focusing on mismatches uniquely exhibited by the de novo DSA allele, rather than mismatches shared by both DSA and non-DSA alleles. This concept paper illustrates several examples, highlights the need for center-specific or population-specific cutoff values for posttransplant risk stratification, and mostly argues that if there is no direct correlation between molecular mismatch load and immunogenicity, then molecular mismatch load must not be adopted as an approach for equitable organ allocation.
    MeSH term(s) Amino Acid Sequence ; Epitope Mapping ; Epitopes/immunology ; Female ; Follow-Up Studies ; Graft Rejection/diagnosis ; Graft Rejection/etiology ; Graft Rejection/pathology ; Graft Survival/immunology ; HLA Antigens/chemistry ; HLA Antigens/immunology ; Histocompatibility/immunology ; Humans ; Isoantibodies/adverse effects ; Kidney Failure, Chronic/immunology ; Kidney Failure, Chronic/surgery ; Kidney Transplantation/adverse effects ; Male ; Middle Aged ; Models, Molecular ; Prognosis ; Protein Conformation ; Risk Factors ; Sequence Homology
    Chemical Substances Epitopes ; HLA Antigens ; Isoantibodies
    Language English
    Publishing date 2019-07-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.15489
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  9. Article ; Online: Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report.

    Tambur, Anat R / Bestard, Oriol / Campbell, Patricia / Chong, Anita S / Barrio, Martha Crespo / Ford, Mandy L / Gebel, Howard M / Heidt, Sebastiaan / Hickey, Michelle / Jackson, Annette / Kosmoliaptsis, Vasilis / Lefaucheur, Carmen / Louis, Kevin / Mannon, Roslyn B / Mengel, Michael / Morris, Anna / Pinelli, David F / Reed, Elaine F / Schinstock, Carrie /
    Taupin, Jean-Luc / Valenzuela, Nicole / Wiebe, Chris / Nickerson, Peter

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2023  Volume 23, Issue 1, Page(s) 133–149

    Abstract: The Sensitization in Transplantation: Assessment of Risk workgroup is a collaborative effort of the American Society of Transplantation and the American Society of Histocompatibility and Immunogenetics that aims at providing recommendations for clinical ... ...

    Abstract The Sensitization in Transplantation: Assessment of Risk workgroup is a collaborative effort of the American Society of Transplantation and the American Society of Histocompatibility and Immunogenetics that aims at providing recommendations for clinical testing, highlights gaps in current knowledge, and proposes areas for further research to enhance histocompatibility testing in support of solid organ transplantation. This report provides updates on topics discussed by the previous Sensitization in Transplantation: Assessment of Risk working groups and introduces 2 areas of exploration: non-human leukocyte antigen antibodies and utilization of human leukocyte antigen antibody testing measurement to evaluate the efficacy of antibody-removal therapies.
    MeSH term(s) Organ Transplantation/adverse effects ; Risk Factors ; Histocompatibility ; Histocompatibility Testing ; Group Processes ; Graft Rejection/etiology ; Isoantibodies
    Chemical Substances Isoantibodies
    Language English
    Publishing date 2023-01-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1016/j.ajt.2022.11.009
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  10. Article ; Online: Signaling through the Inhibitory Fc Receptor FcγRIIB Induces CD8

    Morris, Anna B / Farley, Clara R / Pinelli, David F / Adams, Layne E / Cragg, Mark S / Boss, Jeremy M / Scharer, Christopher D / Fribourg, Miguel / Cravedi, Paolo / Heeger, Peter S / Ford, Mandy L

    Immunity

    2020  Volume 52, Issue 1, Page(s) 136–150.e6

    Abstract: ... Effector ... ...

    Abstract Effector CD8
    MeSH term(s) Adult ; Aged ; Animals ; Apoptosis/immunology ; CD8-Positive T-Lymphocytes/immunology ; Caspase 3/immunology ; Caspase 7/immunology ; Cell Line, Tumor ; Female ; Fibrinogen/genetics ; Fibrinogen/immunology ; Graft Rejection/immunology ; Humans ; Immunoglobulin G/immunology ; Immunosuppression Therapy ; Male ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Receptors, IgG/genetics ; Receptors, IgG/immunology ; Young Adult
    Chemical Substances FCGR2B protein, human ; FGL2 protein, human ; Immunoglobulin G ; Receptors, IgG ; Fibrinogen (9001-32-5) ; CASP3 protein, human (EC 3.4.22.-) ; CASP7 protein, human (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-) ; Caspase 7 (EC 3.4.22.-)
    Language English
    Publishing date 2020-01-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2019.12.006
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