Gene Expression Changes Are Associated With Loss of Kidney Graft Function and Interstitial Fibrosis and Tubular Atrophy: Diagnosis Versus Prediction

Scian, Mariano J.; Maluf, Daniel G.; Archer, Kellie J.; Suh, Jihee L.; Massey, David; Fassnacht, Ryan; Whitehill, B. C.; Sharma, Amit; King, Anne; Gehr, Todd W.B.; Cotterell, Adrian; Posner, Marc P.; Mas, Valeria R.

doi:10.1097/tp.0b013e3182094a5a

Cited by 30 publications

(34 citation statements)

References 41 publications

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“…[24][25][26][27]38 miR-142-3p expression has also been associated with tubular atrophy and interstitial fibrosis of renal transplants. 22 Moreover, miR-142-3p was overexpressed in B lymphocytes from the blood of operationally tolerant patients, and this analysis performed in peripheral blood does not exclude a different expression profile within the graft itself. In addition, we did not find any correlation between miR-142-3p expression and posttransplantation time and did find miR-142-3p expression to be stable over time ( Figure 2C); these results indicate that miR-142-3p is independent of post-transplantation time.…”

Section: Discussionmentioning

confidence: 99%

“…18 Numerous studies have reported on the differential expression of miRNA in physiologic disorders or diseases, 19,20 and miRNA has been found to be modulated in biopsy specimens from kidney transplant recipients. [21][22][23] In this study, we investigated whether miRNA is modulated in the blood of patients with operational tolerance compared with a cohort of patients with stable graft function under classic immunosuppression.…”

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confidence: 99%

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Upregulation of miR-142-3p in Peripheral Blood Mononuclear Cells of Operationally Tolerant Patients with a Renal Transplant

Danger

Pallier²,

Giral³

et al. 2012

Journal of the American Society of Nephrology

105

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Achieving drug-free tolerance or successfully using only small doses of immunosuppression is a major goal in organ transplantation. To investigate the potential mechanisms by which some kidney transplant recipients can achieve operational tolerance, we compared the expression profiles of microRNA in peripheral blood mononuclear cells of operationally tolerant patients with those of stable patients treated with conventional immunosuppression. B cells from operationally tolerant patients overexpressed miR-142-3p. The expression of miR-142-3p was stable over time and was not modulated by immunosuppression. In Raji B cells, overexpression of miR-142-3p modulated nearly 1000 genes related to the immune response of B cells, including potential miR-142-3p targets and molecules previously identified in the blood of operationally tolerant patients. Furthermore, our results suggested that a negative feedback loop involving TGF-b signaling and miR-142-3p expression in B cells may contribute to the maintenance of tolerance. In summary, miR-142-3p expression in peripheral blood mononuclear cells correlates with operational tolerance. Whether upregulation of miR-142-3p modulates inflammatory responses to promote tolerance or is a result of this tolerance state requires further study.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Upregulation of miR-142-3p in Peripheral Blood Mononuclear Cells of Operationally Tolerant Patients with a Renal Transplant

Danger

Pallier²,

Giral³

et al. 2012

Journal of the American Society of Nephrology

105

View full text Add to dashboard Cite

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“…Scian et al demonstrated that genes upregulated in IFTA are primarily involved in pathways related to T-cell activation, NK cell-mediated cytotoxicity, and programmed cell death [24] . To date, there is no corroborating evidence for NK or NKT cells being the cause of IFTA after kidney transplantation.…”

Section: Discussionmentioning

confidence: 99%

Interpreting CD56+ and CD163+ Infiltrates in Early versus Late Renal Transplant Biopsies

Shin

Kim²,

Cho³

et al. 2015

Am J Nephrol

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Background: CD56+ and CD163+ cell infiltration in human kidney transplant biopsies have not been fully evaluated. Methods: We investigated the association of CD56+ and CD163+ cell infiltration with human kidney transplant biopsies with antibody- or T-cell-mediated rejection (TCMR) and other histologic lesions. One hundred and seventy four clinically indicated transplant biopsies were included in this analysis. Immunohistochemical staining for C4d, CD56 and CD163 was performed. Results: One hundred and seventy four indication biopsies were divided into early (≤1 year posttransplant; n = 49) and late (>1 year posttransplant; n = 125) biopsies. High numbers of CD56+ cells were uncommon in early biopsies except for those with antibody-mediated rejection (AMR) only. On the other hand, high numbers of CD56+ cells were observed in late biopsies diagnosed as TCMR only, AMR only, and TCMR combined with AMR. In early biopsies, both CD56+ and CD163+ infiltrates correlated strongly with interstitial inflammation, tubulitis, and peritubular capillaritis (ptc) scores. The ci and ct scores, however, were correlated only with the number of CD56+ cells. In late biopsies, on the other hand, the number of CD56+ infiltrates was correlated only with ptc, while the number of CD163+ infiltrates was weakly correlated with any histologic lesion. Multivariable analyses showed that chronic active AMR and the number of CD56+ cells/10 HPF were independently associated with death-censored graft failure post-biopsy. The number of CD163+ cells was not correlated with any pathologic lesion and post-biopsy graft failure. CD56+ infiltrates were also associated with interstitial fibrosis and tubular atrophy. Conclusions: Intragraft CD56+ cell infiltrates were significantly associated with AMR and subsequent poor clinical outcomes.

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“…Renal biopsy tissue can also be used for unbiased approaches such as microarray analyses, which may yield diagnostic molecular signatures (213,(369)(370)(371)(372)(373)(374). This ''molecular microscope'' has been shown to improve the diagnosis of rejection but also to reflect molecular alterations in fibrosis (375)(376)(377)(378).…”

Section: Diagnosis Of Renal Fibrosismentioning

confidence: 99%

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Floege

2015

American Journal of Transplantation

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Gene Expression Changes Are Associated With Loss of Kidney Graft Function and Interstitial Fibrosis and Tubular Atrophy: Diagnosis Versus Prediction

Abstract: An IF/TA gene expression signature was identified, and it was useful for diagnosis but not prediction. However, gene expression profiles at 3 months might predict IF/TA progression.

Cited by 30 publications

References 41 publications

Upregulation of miR-142-3p in Peripheral Blood Mononuclear Cells of Operationally Tolerant Patients with a Renal Transplant

Upregulation of miR-142-3p in Peripheral Blood Mononuclear Cells of Operationally Tolerant Patients with a Renal Transplant

Interpreting CD56+ and CD163+ Infiltrates in Early versus Late Renal Transplant Biopsies

Renal Allograft Fibrosis: Biology and Therapeutic Targets

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