Molecular Diagnosis of Renal-Allograft Rejection: Correlation with Histopathologic Evaluation and Antirejection-Therapy Resistance

Desvaux, Dominique; Schwarzinger, Michaël; Pastural, Myriam; Baron, Christophe; Abtahi, Maryam Sadat; Berrehar, François; Lim, Annick; Lang, Philippe; Gouvello, Sabine Le

doi:10.1097/01.tp.0000133530.26680.dc

Cited by 47 publications

(37 citation statements)

References 25 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Upregulation of intragraft granzyme B and perforin also has been seen, again supporting the role of the cytotoxic T cell in allograft rejection (63). This observation also has been confirmed using real-time technology with high sensitivity (90%) and specificity (74%) for granzyme B as well as FasL (64). Moreover, the presence of enhanced expression of FasL more often was associated with therapeutic resistance to treatment.…”

Section: What More Can the Biopsy Tell Us?supporting

confidence: 56%

Beyond Histology

Mannon¹,

Kirk²

2006

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Kidney biopsy is the gold standard procedure for the assessment of allograft dysfunction. The differential diagnosis for both acute and chronic dysfunction can encompass a number of different causes, and a biopsy frequently can suggest a specific cause. However, many of these causes are difficult to distinguish on morphologic basis alone, and the information that is obtained from a biopsy is limited with regard to functional and prognostic importance. Additional methods therefore are needed to guide the diagnosis and the treatment of allograft dysfunction, and numerous methods have been studied. Potential markers include protein and gene expression profiles in the peripheral blood, the urine, and the graft itself, all compartments that are relevant to the alloimmune response. Recent comprehensive sequencing of the human genome has led to an unprecedented opportunity to develop these genetic and proteomic techniques, and ongoing evaluations of potential tests have led to an improved understanding of the complexity of immune responses. The future challenge for promising tests is validation in larger patient populations to facilitate their addition to the diagnostic armamentarium.

show abstract

Section: What More Can the Biopsy Tell Us?supporting

confidence: 56%

Beyond Histology

Mannon¹,

Kirk²

2006

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…We previously demonstrated that the activity levels of the cytotoxic molecules Granzyme B (GB) and Fas ligand and the regulatory T cell (Treg) marker Foxp3, from the intragraft infiltrate of biopsies with BL changes, are intermediate, between those associated with TCMR and absence of rejection. 6,7 We also quantified the Foxp3/GB ratio to determine the relative proportions of alloaggressive and graft-protecting T cells. T cell infiltrate from biopsies with BL changes had a significantly higher ratio than in grade IA acute rejection biopsies, although the distribution of both markers was heterogeneous in all groups.…”

mentioning

confidence: 99%

Intragraft Levels of Foxp3 mRNA Predict Progression in Renal Transplants with Borderline Change

Mansour

Homs²,

Desvaux³

et al. 2008

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

“…This indicates that the presence of cytotoxic lymphocytes within an allograft is not necessarily harmful. Several studies have already shown comparable results employing biopsy material or urine [5,6,8,9,10,11,12], commonly demonstrating CTL-associated gene expression in kidneys without rejection. Nevertheless, levels of perforin and granzyme B increased with Banff rejection grades.…”

Section: Discussionmentioning

confidence: 70%

“…Recent studies emphasized the importance of T lymphocytes, but also of B cells in rejection and immunologic injury [1,2,3,4]. Detection of cytotoxic T cell transcripts, such as granzyme B, perforin or granulysin, in RNA extracts from transplanted kidneys, urine or peripheral blood allowed reliable diagnoses of acute rejection episodes [5,6,7,8,9,10,11], even at the subclinical level [12]. Furthermore, inflammatory proteins involved in fibrogenesis or cellular senescence were reported to be activated in chronically deteriorating transplants [13,14,15].…”

Section: Introductionmentioning

confidence: 99%

Local Expression of C-Reactive Protein Is Associated with Deteriorating Graft Function in Acute and Chronic Failure of Kidney Transplants

Jabs¹,

Meier²,

Lamprecht

et al. 2010

Nephron Clin Pract

View full text Add to dashboard Cite

Background: C-reactive protein (CRP) is a key molecule in inflammation and tissue homeostasis and is produced locally by renal tubular epithelial cells. Its significance of expression in contrast to expression of cytotoxic T cell (CTL) markers remains to be elucidated. Methods: By means of real-time PCR, we determined mRNA levels of CRP in 66 renal allograft biopsies with acute allograft failure and in 34 biopsies with chronic dysfunction. Results were compared to expression of CTL components (perforin, granzyme B) and were correlated with histologic diagnoses and outcome. Results: CTL markers were found in most biopsies, and thus were not specific for particular histologies, although expression levels increased significantly with Banff rejection grades. Expression of CRP was highly specific for rejection episodes in acute failure (p < 0.0001) as well as for transplant glomerulopathy or de novo/recurrent glomerulonephritis in chronic failure (p < 0.005). Finally, the presence of CRP expression in renal allografts was associated with a deteriorating 1-year graft function in acute (p < 0.01) as well as chronic allograft dysfunction (p = 0.077). Conclusions: Our data suggest local CRP expression of kidney transplants as an indicator for pathologic entities associated with unfavorable outcomes in the early and late course of kidney transplants.

show abstract

Molecular Diagnosis of Renal-Allograft Rejection: Correlation with Histopathologic Evaluation and Antirejection-Therapy Resistance

Cited by 47 publications

References 25 publications

Beyond Histology

Beyond Histology

Intragraft Levels of Foxp3 mRNA Predict Progression in Renal Transplants with Borderline Change

Local Expression of C-Reactive Protein Is Associated with Deteriorating Graft Function in Acute and Chronic Failure of Kidney Transplants

Contact Info

Product

Resources

About