An Insight Into the Immunologic Events and Risk Assessment in Renal Transplantation

Khan, Asif; Nasr, P.; El‐Charabaty, Elie; El‐Sayegh, Suzanne

doi:10.14740/jocmr2411w

Cited by 7 publications

(5 citation statements)

References 45 publications

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“…However, the modest improvement of long‐term graft survival over the last decades remains a major concern in the transplant community . Accordingly, novel noninvasive biomarkers that might be of predictive value for assessing long‐term graft survival are currently being intensively investigated . By implementing HLA matching in transplant allocation systems, the transplant field has been among the first to achieve translation of genetic information into improved clinical outcomes through personalized medicine .…”

Section: Introductionmentioning

confidence: 99%

Single Nucleotide Polymorphisms and Long-Term Clinical Outcome in Renal Transplant Patients: A Validation Study

Pihlstrøm

Mjøen

Mucha

et al. 2017

American Journal of Transplantation

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Genome-wide association studies (GWAS) are designed to investigate single nucleotide polymorphisms (SNPs) and the association with a clinical phenotype. A previous GWAS performed in 300 renal transplant recipients identified two SNPs (rs3811321 and rs6565887) associated with serum creatinine and clinical outcome. We sought to validate these findings. Genotyping of the two SNPs was performed using Taqman assays in 1638 Caucasians participating in the Assessment of LEscol in Renal Transplant (ALERT) study. Primary endpoint was death-censored graft loss, and secondary endpoint was all-cause mortality. Applying Cox regression, no crude association to graft loss was found for rs3811321 on chromosome 14 (hazard ratio [HR] 0.87, 95% CI 0.59-1.29, p = 0.50) or rs6565887 on chromosome 18 (HR 0.88, CI 0.62-1.25, p = 0.48). Multivariable adjustments did not change results, nor did evaluation of the number of risk alleles formed by the two SNPs. No association with mortality was detected. In conclusion, an impact of two SNPs on chromosomes 14 and 18 on death-censored graft survival or all-cause mortality was not confirmed. Our results emphasize the importance of validating findings from high-throughput genetics studies and call for large collaborative research initiatives in the field of transplantation outcomes.

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Section: Introductionmentioning

confidence: 99%

Single Nucleotide Polymorphisms and Long-Term Clinical Outcome in Renal Transplant Patients: A Validation Study

Pihlstrøm

Mjøen

Mucha

et al. 2017

American Journal of Transplantation

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“… 10 Immunosuppressants are usually used in clinical practice to reduce the risk of postoperative rejection. 11 However, long-term use of immunosuppressants can cause side effects, including inhibition of immune functions and adverse drug reactions.…”

Section: Introductionmentioning

confidence: 99%

“…They can bind to the mRNAs of their target genes in a sequence-specific manner, resulting in degradation of the mRNA or inhibition of translation; therefore, miRNAs have important roles in biological development, cell differentiation, cell apoptosis and tumor development. 12–14 Although studies have confirmed the roles of miRNAs in human organ transplantation, 11–13 there are few reports on miRNAs directly associated with corneal transplantation rejection. miR-466 and miR-184 are reported to be closely related with corneal lymphangiogenesis.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-122 ameliorates corneal allograft rejection through the downregulation of its target CPEB1

Wang

et al. 2017

Cell Death Discov.

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Transplant rejection is a major cause of corneal transplantation failure. MicroRNAs (miRNAs) are a family of small RNAs that regulates gene expression in a sequence-specific manner. miRNAs have recently been shown to have important roles in human organ transplantation, but reports of miRNAs directly associated with corneal transplantation rejection remain limited. To investigate the role of miRNAs during corneal allograft rejection, we established a mouse penetrating keratoplasty model and used microarrays to screen for differentially expressed miRNAs. Our results revealed that the expression of miR-122 was significantly decreased in the allogeneic group. Consistent with this result, the expression of cytoplasmic polyadenylation element-binding protein-1 (CPEB1), a direct target of miR-122, was significantly increased. Further analysis demonstrated that miR-122 inhibited inflammatory cytokine-induced apoptosis in corneal keratocytes through the downregulation of its target CPEB1. We also found that increased miR-122 expression significantly reduced the risk of corneal transplantation rejection. Thus, our results indicate that miR-122 is an important miRNA associated with corneal graft rejection and can be used as a therapeutic target for the prevention of immune rejection after keratoplasty.

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“…MicroRNAs (miRNA), a class of small ncRNAs of approximately 21-24 nucleotides (nt) in length [98,99], have been shown to play different roles in human organ transplantations [100,101]. However, there are only a few reports on miRNAs being directly associated with corneal transplant rejection.…”

Section: Non-coding Rnas In Lymphangiogenesismentioning

confidence: 99%

Role of Endogenous Regulators of Hem- And Lymphangiogenesis in Corneal Transplantation

Clahsen

Büttner

Hatami

et al. 2020

JCM

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Under normal conditions, the cornea, being the transparent "windscreen" of the eye, is free of both blood and lymphatic vessels. However, various diseases of the eye, like infections, can interfere with the balance between promoting and inhibiting factors, which leads to ingrowth of blood and lymphatic vessels. The newly formed lymphatic vessels increase the risk of graft rejection after subsequent corneal transplantation. Corneal transplantation is one of the most commonly performed transplantations worldwide, with more than 40,000 surgeries per year in Europe. To date, various anti-hem-and anti-lymphangiogenic treatment strategies have been developed specifically for the corneal vascular endothelial growth factor (VEGF) pathway. Currently, however, no treatment strategies are clinically available to specifically modulate lymphangiogenesis. In this review, we will give an overview about endogenous regulators of hem-and lymphangiogenesis and discuss potential new strategies for targeting pathological lymphangiogenesis. Furthermore, we will review recently identified modulators and demonstrate that the cornea is a suitable model for the identification of novel endogenous modulators of lymphangiogenesis. The identification of novel modulators of lymphangiogenesis and a better understanding of the signaling pathways involved will contribute to the development of new therapeutic targets for the treatment of pathological lymphangiogenesis. This, in turn, will improve graft rejection, not only for the cornea.

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An Insight Into the Immunologic Events and Risk Assessment in Renal Transplantation

Cited by 7 publications

References 45 publications

Single Nucleotide Polymorphisms and Long-Term Clinical Outcome in Renal Transplant Patients: A Validation Study

Single Nucleotide Polymorphisms and Long-Term Clinical Outcome in Renal Transplant Patients: A Validation Study

MicroRNA-122 ameliorates corneal allograft rejection through the downregulation of its target CPEB1

Role of Endogenous Regulators of Hem- And Lymphangiogenesis in Corneal Transplantation

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