Renal expression of CD44 correlates with acute renal allograft rejection

Rouschop, Kasper M.A.; Roelofs, Joris J. T. H.; Sylva, Marc; Rowshani, Ajda T.; Berge, Ineke J. M. ten; Weening, Jan J.; Florquin, Sandrine

doi:10.1038/sj.ki.5001711

Cited by 29 publications

(22 citation statements)

References 42 publications

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“…The abundance of CXCL9 in urine [24] and that of soluble CD44 in plasma [25] have previously been shown to increase in renal AR compared with STA. In addition, macrophage surface PECAM1 can distinguish lung transplant rejection [41] but is not diagnostic in mouse models of cardiac transplant rejection [42].…”

Section: Discussionmentioning

confidence: 97%

“…For example, in renal transplant rejection, significantly increased protein concentrations of VEGF have been observed in serum and urine [21], [22], [23]. Increases in the following other entities have also been observed: CXCL9 in urine [24], soluble CD44 in plasma [25], ADL in serum [26], and TNF-alpha in serum [27]. HLA class I (ABC) protein levels were recently found to be elevated on the surfaces of peripheral blood CD3+/CD8+ T lymphocytes in AR at 14 and 21 days after renal transplantation [28].…”

Section: Introductionmentioning

confidence: 99%

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Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-Organ Transplant Rejection and Other Conditions

Chen

Sigdel

et al. 2010

PLoS Comput Biol

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Serum proteins are routinely used to diagnose diseases, but are hard to find due to low sensitivity in screening the serum proteome. Public repositories of microarray data, such as the Gene Expression Omnibus (GEO), contain RNA expression profiles for more than 16,000 biological conditions, covering more than 30% of United States mortality. We hypothesized that genes coding for serum- and urine-detectable proteins, and showing differential expression of RNA in disease-damaged tissues would make ideal diagnostic protein biomarkers for those diseases. We showed that predicted protein biomarkers are significantly enriched for known diagnostic protein biomarkers in 22 diseases, with enrichment significantly higher in diseases for which at least three datasets are available. We then used this strategy to search for new biomarkers indicating acute rejection (AR) across different types of transplanted solid organs. We integrated three biopsy-based microarray studies of AR from pediatric renal, adult renal and adult cardiac transplantation and identified 45 genes upregulated in all three. From this set, we chose 10 proteins for serum ELISA assays in 39 renal transplant patients, and discovered three that were significantly higher in AR. Interestingly, all three proteins were also significantly higher during AR in the 63 cardiac transplant recipients studied. Our best marker, serum PECAM1, identified renal AR with 89% sensitivity and 75% specificity, and also showed increased expression in AR by immunohistochemistry in renal, hepatic and cardiac transplant biopsies. Our results demonstrate that integrating gene expression microarray measurements from disease samples and even publicly-available data sets can be a powerful, fast, and cost-effective strategy for the discovery of new diagnostic serum protein biomarkers.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-Organ Transplant Rejection and Other Conditions

Chen

Sigdel

et al. 2010

PLoS Comput Biol

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“…OPN is a multifunctional bone regulatory protein that is upregulated by phos and acts as a potent macrophage-chemotactic stimulant (25). In an animal model, a high-phos diet was shown to upregulate OPN expression in renal tubules (29), and kidney transplant patients with rejection were found to have significantly enhanced OPN expression in tissue biopsy (30,31).…”

Section: Discussionmentioning

confidence: 99%

Donor Phosphorus Levels and Recipient Outcomes in Living-Donor Kidney Transplantation

Chang¹,

Saha²,

Gomes³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives In living-donor kidney transplantation, various donor factors, including gender, age, and baseline kidney function, predict allograft function and recipient outcomes after transplantation. Because higher phosphorus is predictive of vascular injury in healthy adults, the effect of donor phosphorus levels on recipient renal function after transplantation was investigated.Design, setting, participants, and measurements Phosphorus levels in 241 living donors were analyzed from a 7-year period, and recipient renal function and acute rejection at 1 year posttransplantation were examined controlling for other influencing factors, including multiple donor variables, HLA matching, and acute rejection.Results Female and African-American donors had significantly higher phosphorus levels predonation. By multivariable analysis, higher donor phosphorus correlated with higher recipient serum creatinine (slope ϭ 0.087, 95% confidence interval [CI]: 0.004 to 0.169, P ϭ 0.041) and lower recipient estimated GFR (slope ϭ Ϫ4.321, 95% CI: Ϫ8.165 to Ϫ0.476, P ϭ 0.028) at 12 months. Higher donor phosphorus also displayed an independent correlation with biopsy-proven acute rejection and delayed or slow graft function after transplantation. ConclusionsIn a cohort of living kidney donors, higher donor phosphorus correlated with female gender and African-American ethnicity and was an independent risk factor for early allograft dysfunction after living-donor kidney transplantation.

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“…Numerous studies have described the renal accumulation of CD44, an adhesion molecule involved in cell differentiation, and its main ligand, Hyaluronan (HA), a matrix glycosaminoglycan, in various renal diseases such as ischemia-reperfusion, lithiasis, or renal allograft rejection [8][9][10][11][12][13]. CD44 is a glycoprotein involved in cell-cell and cellmatrix interactions, in particular cell migration and tissue repair.…”

Section: Introductionmentioning

confidence: 99%

CD44-Positive Cells and Hyaluronan are a Hallmark of a Rat Model of Aristolochic Acid Nephropathy

et al. 2013

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Background: Aristolochic acid (AA) Nephropathy (AAN) is characterized by tubulointerstitial injury leading to fibrosis and tubular atrophy. Defective regeneration of tubular cells was hypothesized as a mechanism leading to Proximal Tubular Epithelial Cell (PTEC) atrophy. Here, we examined the distribution of CD44, an adhesion molecule involved in differentiation, and its main ligand, Hyaluronan (HA), in an experimental AAN model.

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Renal expression of CD44 correlates with acute renal allograft rejection

Cited by 29 publications

References 42 publications

Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-Organ Transplant Rejection and Other Conditions

Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-Organ Transplant Rejection and Other Conditions

Donor Phosphorus Levels and Recipient Outcomes in Living-Donor Kidney Transplantation

CD44-Positive Cells and Hyaluronan are a Hallmark of a Rat Model of Aristolochic Acid Nephropathy

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