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  1. Article ; Online: Management of the sensitized pediatric renal transplant candidate.

    Puliyanda, Dechu P / Jordan, Stanley C

    Pediatric transplantation

    2024  Volume 28, Issue 2, Page(s) e14694

    Abstract: Kidney transplantation is the treatment of choice for patients with ESRD as it is associated with improved patient survival and better quality of life, especially in children. There are several barriers to a successful transplant including organ shortage, ...

    Abstract Kidney transplantation is the treatment of choice for patients with ESRD as it is associated with improved patient survival and better quality of life, especially in children. There are several barriers to a successful transplant including organ shortage, anatomic barriers, and immunologic barriers. One of the biggest immunologic barriers that precludes transplantation is sensitization, when patients have antibodies prior to transplantation, resulting in positive crossmatches with donor. 30%-40% of adult patients on the wait list are sensitized. There is a growing number of pediatric patients on the wait list who are sensitized. This poses a unique challenge to the pediatric transplant community. Therefore, attempts to perform desensitization to remove or suppress pathogenic HLA antibodies resulting in acceptable crossmatches, and ultimately a successful transplant, while reducing the risk of acute rejection, are much needed in these children. This review article aims to address the management of such patients both prior to transplantation, with strategies to overcome sensitization, and after transplantation with monitoring for allograft rejection and other complications.
    MeSH term(s) Adult ; Humans ; Child ; Kidney Transplantation/methods ; Quality of Life ; Immunoglobulins, Intravenous ; Desensitization, Immunologic/methods ; Histocompatibility Testing ; Antibodies ; Graft Rejection/prevention & control ; HLA Antigens
    Chemical Substances Immunoglobulins, Intravenous ; Antibodies ; HLA Antigens
    Language English
    Publishing date 2024-02-23
    Publishing country Denmark
    Document type Journal Article ; Review
    ZDB-ID 1390284-2
    ISSN 1399-3046 ; 1397-3142
    ISSN (online) 1399-3046
    ISSN 1397-3142
    DOI 10.1111/petr.14694
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    Zs.A 4947: Show issues Location:
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  2. Article: Assessment of IgM DSAs in Transplant Recipients: Relationship to De Novo IgG DSAs and Risk for Antibody Rejection.

    Zhang, Xiaohai / Jordan, Stanley C

    Transplantation direct

    2024  Volume 10, Issue 3, Page(s) e1583

    Abstract: Background: The presence of anti-HLA donor-specific antibodies (DSAs) is associated with antibody-mediated rejection (AMR) and inferior graft survival. However, recent data suggest that ~50% of AMR episodes are IgG DSA negative and possibly related to ... ...

    Abstract Background: The presence of anti-HLA donor-specific antibodies (DSAs) is associated with antibody-mediated rejection (AMR) and inferior graft survival. However, recent data suggest that ~50% of AMR episodes are IgG DSA negative and possibly related to non-HLA DSAs. After the initial activation of B cells to alloantigen, IgM is the first immunoglobulin produced. In addition, both IgM and IgG isotopes can activate the classic complement pathway and induce complement-dependent cytotoxicity to allograft targets. Current practices focus on the assessment of IgG DSAs with little concern for the assessment of IgM DSAs.
    Methods: Here, we examined anti-HLA IgM in a cohort of 22 patients who developed de novo IgG DSAs by a modified single-antigen bead-based test.
    Results: We found IgM HLA DSAs developed before IgG DSAs. The median time from the detection of IgM DSAs to the appearance of de novo IgG DSAs was 461 d. Most patients had IgM DSAs against the same HLA-DQ antigens, for which IgG de novo DSAs were also later detected. IgM DSAs were detected in patients with biopsies suspected of AMR.
    Conclusions: The detection of IgM DSAs could be an early indicator of alloimmune responses to allografts before IgG de novo DSAs appear.
    Language English
    Publishing date 2024-02-16
    Publishing country United States
    Document type Journal Article
    ISSN 2373-8731
    ISSN 2373-8731
    DOI 10.1097/TXD.0000000000001583
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  3. Article ; Online: Obinutuzumab for Desensitization: An Unexpected Benefit?

    Jordan, Stanley C

    Transplantation

    2021  Volume 106, Issue 2, Page(s) 245–247

    MeSH term(s) Antibodies, Monoclonal, Humanized/adverse effects ; Rituximab
    Chemical Substances Antibodies, Monoclonal, Humanized ; Rituximab (4F4X42SYQ6) ; obinutuzumab (O43472U9X8)
    Language English
    Publishing date 2021-02-08
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000003687
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  4. Article ; Online: Immune response to non-HLA antigens and renal allograft loss.

    Jordan, Stanley C

    Lancet (London, England)

    2019  Volume 393, Issue 10174, Page(s) 854–856

    MeSH term(s) Allografts ; Kidney Transplantation ; Prospective Studies ; Tissue Donors ; Transplantation, Homologous
    Language English
    Publishing date 2019-02-14
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(18)33186-6
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  5. Article ; Online: Donor-derived cell-free DNA in kidney transplantation: evolving concepts and potential limitations.

    Huang, Edmund / Jordan, Stanley C

    Kidney international

    2022  Volume 101, Issue 4, Page(s) 676–677

    Abstract: Bu et al. report that elevated donor-derived cell-free DNA detected on serial measurements performed for both surveillance and assessment of kidney allograft dysfunction was associated with rejection, future de novo donor-specific antibodies, and decline ...

    Abstract Bu et al. report that elevated donor-derived cell-free DNA detected on serial measurements performed for both surveillance and assessment of kidney allograft dysfunction was associated with rejection, future de novo donor-specific antibodies, and decline in estimated glomerular filtration rate. Their data suggest that donor-derived cell-free DNA may be a useful indicator of kidney allograft health. In this commentary, we discuss the expanding role of donor-derived cell-free DNA for allograft surveillance and highlight potential limitations.
    MeSH term(s) Cell-Free Nucleic Acids ; Glomerular Filtration Rate ; Graft Rejection/epidemiology ; Graft Rejection/genetics ; Graft Rejection/prevention & control ; Humans ; Kidney Transplantation/adverse effects ; Tissue Donors
    Chemical Substances Cell-Free Nucleic Acids
    Language English
    Publishing date 2022-03-21
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2022.01.012
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    Zs.A 797: Show issues Location:
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  6. Article ; Online: Novel therapies for treatment of antibody-mediated rejection of the kidney.

    Sethi, Supreet / Jordan, Stanley C

    Current opinion in organ transplantation

    2022  Volume 28, Issue 1, Page(s) 29–35

    Abstract: Purpose of review: We aim to discuss current literature on novel therapies for antibody-mediated rejection (AMR) in kidney transplantation with a focus on chronic AMR.: Recent findings: IL-6/IL-6 receptor blockers appear promising in the treatment of ...

    Abstract Purpose of review: We aim to discuss current literature on novel therapies for antibody-mediated rejection (AMR) in kidney transplantation with a focus on chronic AMR.
    Recent findings: IL-6/IL-6 receptor blockers appear promising in the treatment of chronic AMR. Blocking this pathway was shown to reduce human leucocyte antigen-antibodies, improve histologic inflammation and increase T-regulatory cells. Based on experience in desensitization, IgG degrading endopeptidase, imlifidase, could be effective in AMR. There have been case reports describing the successful use of plasma cell/natural killer-cell-directed anti-CD38 antibody in the treatment of AMR. Off-target effects have been noted and strategies to mitigate these will be needed when using these agents. Complement inhibitors could be an effective add-on strategy to antibody-depleting therapies but their role in AMR needs to be better defined. Combining proteasome inhibitors and costimulation blockers has shown encouraging results in the prevention of AMR in animal models and is now being investigated in humans. Other novel strategies such as Fc neonatal receptor blockers which inhibit the recycling of pathogenic IgG and bispecific antibodies against B-cell maturation antigen/CD3+ T cells warrant further investigation.
    Summary: There are now a number of emerging therapies with varied targets and mechanism(s) of action that hold promise in the management of AMR and improving allograft survival.
    MeSH term(s) Animals ; Infant, Newborn ; Humans ; Graft Rejection/drug therapy ; Graft Rejection/prevention & control ; Immunosuppressive Agents/therapeutic use ; Kidney Transplantation/adverse effects ; Kidney ; Immunoglobulin G ; Isoantibodies
    Chemical Substances Immunosuppressive Agents ; Immunoglobulin G ; Isoantibodies
    Language English
    Publishing date 2022-11-24
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 1390429-2
    ISSN 1531-7013 ; 1087-2418
    ISSN (online) 1531-7013
    ISSN 1087-2418
    DOI 10.1097/MOT.0000000000001037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5609: Show issues Location:
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  7. Article ; Online: Advances in desensitization for human leukocyte antigen incompatible kidney transplantation.

    Vo, Ashley / Ammerman, Noriko / Jordan, Stanley C

    Current opinion in organ transplantation

    2023  Volume 29, Issue 2, Page(s) 104–120

    Abstract: Purpose of review: Human leukocyte antigen (HLA) sensitization is a major barrier to kidney transplantation induced by exposure to alloantigens through pregnancy, blood product exposure and previous transplantations. Desensitization strategies are ... ...

    Abstract Purpose of review: Human leukocyte antigen (HLA) sensitization is a major barrier to kidney transplantation induced by exposure to alloantigens through pregnancy, blood product exposure and previous transplantations. Desensitization strategies are undertaken to improve the chances of finding compatible organ offers. Standard approaches to desensitization include the use of plasmapheresis/low dose intravenous immunoglobulin (IVIG) or high dose IVIG plus anti-CD20. However, current methods to reduce HLA antibodies are not always successful, especially in those with calculated panel reactive antibody 99-100%.
    Recent findings: Newer desensitization strategies such as imlifidase [immunoglobulin G (IgG) endopeptidase] rapidly inactivates IgG molecules and creates an "antibody-free zone", representing an important advancement in desensitization. However, pathogenic antibodies rebound, increasing allograft injury that is not addressed by imlifidase. Here, use of anti-IL-6R (tocilizumab) or anti-interleukin-6 (clazakizumab) could offer long-term control of B-memory and plasma cell DSA responses to limit graft injury. Agents aimed at long-lived plasma cells (anti-CD38 and anti-BCMAxCD3) could reduce or eliminate HLA-producing plasma cells from marrow niches. Other agents such as complement inhibitors and novel agents inhibiting the Fc neonatal receptor (FcRn) mediated IgG recycling will likely find important roles in desensitization.
    Summary: Use of these agents alone or in combination will likely improve the efficacy and durability of desensitization therapies, improving access to kidney transplantation for immunologically disadvantaged patients.
    MeSH term(s) Infant, Newborn ; Humans ; Kidney Transplantation/adverse effects ; Immunoglobulins, Intravenous/therapeutic use ; Graft Rejection/prevention & control ; Immunosuppressive Agents/adverse effects ; Antibodies ; HLA Antigens ; Desensitization, Immunologic
    Chemical Substances Immunoglobulins, Intravenous ; Immunosuppressive Agents ; Antibodies ; HLA Antigens
    Language English
    Publishing date 2023-12-13
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 1390429-2
    ISSN 1531-7013 ; 1087-2418
    ISSN (online) 1531-7013
    ISSN 1087-2418
    DOI 10.1097/MOT.0000000000001131
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  8. Article ; Online: Reply to Olivera and Mallat.

    Jordan, Stanley C / Huang, Edmund

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2020  Volume 73, Issue 1, Page(s) e272–e273

    Language English
    Publishing date 2020-09-04
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciaa1287
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  9. Article ; Online: Tocilizumab for Covid-19 - The Ongoing Search for Effective Therapies.

    Huang, Edmund / Jordan, Stanley C

    The New England journal of medicine

    2020  Volume 383, Issue 24, Page(s) 2387–2388

    MeSH term(s) Antibodies, Monoclonal, Humanized/therapeutic use ; COVID-19/drug therapy ; Humans ; Pandemics ; SARS-CoV-2
    Chemical Substances Antibodies, Monoclonal, Humanized ; tocilizumab (I031V2H011)
    Language English
    Publishing date 2020-12-18
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMe2032071
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  10. Article ; Online: Obinutuzumab in Kidney Transplantation: Effect on B-cell Counts and Crossmatch Tests.

    Zhang, Xiaohai / Li, Fang / Jordan, Stanley C

    Transplantation

    2021  Volume 105, Issue 11, Page(s) e272–e273

    MeSH term(s) Antibodies, Monoclonal, Humanized ; Cell Count ; Graft Survival ; Histocompatibility Testing ; Kidney Transplantation/adverse effects
    Chemical Substances Antibodies, Monoclonal, Humanized ; obinutuzumab (O43472U9X8)
    Language English
    Publishing date 2021-10-28
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000003849
    Database MEDical Literature Analysis and Retrieval System OnLINE

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