Characteristics of Early Routine Renal Allograft Biopsies

Burdick, James F.; Beschorner, William E.; Smith, William J.; McGraw, Daniel J.; Bender, Walter L.; Williams, Gary M.; Solez, Kim

doi:10.1097/00007890-198412000-00026

Cited by 102 publications

(46 citation statements)

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“…Following transplantation, only a single study has described them in organ biopsies, but not formally demonstrated coexpression of CD4 and CD8 (37). In animal transplantation models, only one study has found such cells in the periphery associated with cyclosporin A treatment (38).…”

Section: Discussionmentioning

confidence: 99%

Isolation of Human CD4/CD8 Double-Positive, Graft-Versus-Host Disease–Protective, Minor Histocompatibility Antigen–Specific Regulatory T Cells and of a Novel HLA-DR7–Restricted HY-Specific CD4 Clone

Eljaafari

Yuruker

Ferrand

et al. 2013

The Journal of Immunology

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Minor histocompatibility (H) Ags are classically described as self-peptides derived from intracellular proteins that are expressed at the cell surface by MHC class I and class II molecules and that induce T cell alloresponses. We have isolated three different T cell populations from a skin biopsy of a patient suffering from acute graft-versus-host disease following sex-mismatched HLA-identical bone marrow transplantation. The first population was: 1) CD4+/CD8+ double-positive; 2) specific for an HLA class I–restricted autosomal Ag; 3) expressed a Tr1 profile with high levels of IL-10, but low IL-2 and IFN-γ; and 4) exerted regulatory function in the presence of recipient APCs. The second was CD8 positive, specific for an HLA class I–restricted autosomally encoded minor H Ag, but was only weakly cytotoxic. The third was CD4 single positive, specific for an HLA-DR7–restricted HY epitope and exerted both proliferative and cytotoxic functions. Identification of the peptide recognized by these latter cells revealed a new human HY epitope, TGKIINFIKFDTGNL, encoded by RPS4Y and restricted by HLA-DR7. In this paper, we show human CD4/CD8 double-positive, acute graft-versus-host disease–protective, minor H Ag–specific regulatory T cells and identify a novel HLA-DR7/ HY T cell epitope, encoded by RPS4Y, a potential new therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Isolation of Human CD4/CD8 Double-Positive, Graft-Versus-Host Disease–Protective, Minor Histocompatibility Antigen–Specific Regulatory T Cells and of a Novel HLA-DR7–Restricted HY-Specific CD4 Clone

Eljaafari

Yuruker

Ferrand

et al. 2013

The Journal of Immunology

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“…A rise in the serum creatinine, without other obvious cause, accompanied by a renal allograft biopsy demonstrating the appropriate histopathologic picture, is the most common presentation (4). However, Rush and his colleagues (5)(6)(7), and others (8)(9)(10)(11), have demonstrated the presence of subclinical acute tubulitis, i.e. histopathologic evidence of acute tubulitis in the presence of stable renal function.…”

Section: Introductionmentioning

confidence: 99%

An Analysis of Early Renal Transplant Protocol Biopsies – the High Incidence of Subclinical Tubulitis

Shapiro

Randhawa

Jordan

et al. 2001

American Journal of Transplantation

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To investigate the possibility that we have been underestimating the true incidence of acute rejection, we began to perform protocol biopsies after kidney transplantation. This analysis looks at the one-week biopsies. Between March 1 and October 1, 1999, 100 adult patients undergoing cadaveric kidney or kidney/pancreas transplantation, or living donor kidney transplantation, underwent 277 biopsies. We focused on the subset of biopsies in patients without delayed graft function (DGF) and with stable or improving renal function, who underwent a biopsy 8.2 ∫ 2.6 d (range 3-18 d) after transplantation (n Ω 28). Six (21%) patients with no DGF and with stable or improving renal function had borderline histopathology, and 7 (25%) had acute tubulitis on the one-week biopsy. Of the 277 kidney biopsies, there was one (0.4%) serious hemorrhagic complication, in a patient receiving low molecular weight heparin; she ultimately recovered and has normal renal function. Her biopsy showed Banff 1B tubulitis. In patients with stable or improving renal allograft function early after transplantation, subclinical tubulitis may be present in a substantial number of patients. This suggests that the true incidence of rejection may be higher than is clinically appreciated.

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“…The implementation of protocol biopsies for early diagnosis has proved to be difficult because of the cost and potential risk to the patients. Although histologic analysis of renal allografts currently is considered to be the best predictor of rejection, recent data suggest that cellular infiltrates are not invariably associated with allograft dysfunction (6,7), and in some instances, such infiltrates may be protective because of the potential action of regulatory T cells (7). In addition, delayed treatment to reverse the process may be costly and/or unsuccessful and even if successful may have a negative impact on long-term graft function and outcome.…”

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confidence: 99%

How Can We Measure Immunologic Tolerance in Humans?

Najafian

Albin²,

Newell³

2006

Journal of the American Society of Nephrology

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Prevention and treatment of allograft rejection in organ transplant recipients relies primarily on non-antigen-specific immunosuppression, with all its associated potential hazards and costs. Currently, the status of the recipient immune response is measured by monitoring pharmacologic drug levels and clinical/pathologic evaluation of graft function. Development of reliable assays that can measure accurately the status of the immune response not only would help clinicians customize the prescription of immunosuppressive drugs in individual patients but also may allow their complete withdrawal in some patients with immunologic tolerance. Furthermore, these assays would facilitate the safe evaluation of novel tolerogenic regimens. Achieving this goal has proved to be very difficult because it requires both a more in-depth understanding of complex mechanisms of tolerance and also identification of transplant patients with acquired tolerance to an allograft that can be studied. This review discusses the current understanding of tolerance mechanisms and outlines the unique and specific challenges in development of tolerance/monitoring assays in the field of transplantation. In addition, several of the most promising candidate assays are discussed in detail.

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Characteristics of Early Routine Renal Allograft Biopsies

Cited by 102 publications

References 0 publications

Isolation of Human CD4/CD8 Double-Positive, Graft-Versus-Host Disease–Protective, Minor Histocompatibility Antigen–Specific Regulatory T Cells and of a Novel HLA-DR7–Restricted HY-Specific CD4 Clone

Isolation of Human CD4/CD8 Double-Positive, Graft-Versus-Host Disease–Protective, Minor Histocompatibility Antigen–Specific Regulatory T Cells and of a Novel HLA-DR7–Restricted HY-Specific CD4 Clone

An Analysis of Early Renal Transplant Protocol Biopsies – the High Incidence of Subclinical Tubulitis

How Can We Measure Immunologic Tolerance in Humans?

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