Analysis of the Major Histocompatibility Complex in Graft Rejection Revisited by Gene Expression Profiles

Christopher, Kenneth B.; Liang, Yurong; Mueller, Thomas; DeFina, Rachel; He, Hongzhen; Haley, Kathleen J.; Exley, Mark A.; Perkins, David L.

doi:10.1097/01.tp.0000128626.13712.88

Cited by 7 publications

(4 citation statements)

References 28 publications

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“…Some studies demonstrated increase in the number of MHC class II-positive cells in the transplanted organs after prolonged ischemic time, [9][10][11][12][13] which is similar to our results using skin model, and it seems that the apparent mechanism of rejection of the allo-transplanted vascularized skin graft by the recipient is similar to those in other reported organs. Increased expression of MHC antigens is induced by inflammatory cytokines such as interferon-g and tumor necrotizing factor-a which would be generated in the damaged tissue.…”

Section: Discussionsupporting

confidence: 93%

“…8 Others have shown that prolonged ischemia of the organs was associated with increased expression of major histocompatibility antigens. [9][10][11][12][13] However, most of the studies failed to show the correlation between ischemic time and extent of rejection of transplanted organs. 1,6 One of the reasons for the difficulty of showing the correlation between ischemic time and extent of rejection of transplants could have originated from the usage of internal organs which are invisible from the outside of the body, and this made it difficult to observe the macroscopic change and to take specimens for microscopic examinations at proper time.…”

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confidence: 94%

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Prolonged ischemia increases severity of rejection in skin flap allotransplantation in rats

et al. 2010

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To investigate the relationship between ischemic time and rejection against allotransplants, vascularized cutaneous flaps from the groin of Brown Norway rats were transplanted to Lewis rats. The ischemic time was set at 1 hour and 6 hours for comparison. Cycrosporine A was used as the immunosuppressant. The results showed more severe rejection in the 6 hours ischemic time group in vivo, and in vitro examination using mixed lymphocyte reaction assay also demonstrated a greater antidonor response in 6 hours-ischemic group than that in 1 hour-group. Immunohistochemical study demonstrated more MHC class II antigen expression in 6 hours-ischemic group than in 1 hour-group. These results suggest that longer ischemic time induces more severe rejection against allo-transplanted tissue compared with the shorter one through an upregulation of MHC class II antigen. It is expected that these findings contribute to the studies for investigating the mechanism of rejection against the allo-transplants.

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Section: Discussionsupporting

confidence: 93%

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confidence: 94%

Prolonged ischemia increases severity of rejection in skin flap allotransplantation in rats

et al. 2010

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“…In addition to their pro‐inflammatory activity, both TNF‐α and IFN‐γ, play a role in HLA‐A and ‐B molecule processing, which leads to a rise in the levels of these antigens (45, 46). Furthermore, it has been shown that HLA‐DR mismatches stimulate IFN‐γ production (47). Unlike the well‐known advantages of HLA matching on transplantation (48, 49), a significant effect was not observed in our patients, probably due to a sample‐size restraint.…”

Section: Discussionmentioning

confidence: 99%

Influence of cytokine and intercellular adhesion molecule‐1 gene polymorphisms on acute rejection in pediatric renal transplantation

Mendoza-Carrera

S²,

Angulo³

et al. 2008

Pediatric Transplantation

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Immune response regulation by cytokines is a key to understanding AGR. The influence of the functional polymorphisms in genes coding for TNF-alpha (-308G > A), IL-10 (-819C > T, and -1082A > G), IFN-gamma [(CA)n], TGF-beta1 (+869T > C), and iCAM-1 (R241G and E469K), in addition to HLA and gender matching on the presentation of AGR in 51 pediatric renal recipients during a 36-month post-transplantation follow-up were analyzed. Also, donors and a control group were genotyped. All groups were within Hardy-Weinberg equilibrium for all polymorphisms except IL-10-819C > T and TNF-alpha (p < 0.005 and p < 0.01, respectively) in recipients. Transplants with gender mismatch showed a higher risk for AGR than those between individuals with gender match (OR, 4.227; p = 0.010). Recipients with a high-production compared with low-production TNF-alpha allele experienced earlier AGR (p = 0.030), and those with high-production alleles of both TNF-alpha and IFN-gamma showed a further increased risk (OR = 11.129, p = 0.024). These findings support the notion that a single genotype cannot by itself explain an event as complex as AGR. The sum or combination of different specific alleles of these genes could better account for the immune response to an allograft.

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“…To address these limitations, the effects of various interventions on grafted organs in mouse and rat models have been assessed using expression microarrays. The overall dynamics of gene expression after cardiac transplant in mice (48)(49)(50)(51) and rats (52, 53) have been assessed. A collection of cytotoxic T-lymphocyte-associated transcripts leading to the development of tubulitis was found in mouse kidney allografts (54).…”

Section: Microarray Gene Expression Analysis Of Nonhuman Transplant Mmentioning

confidence: 99%

Novel Insights into Lung Transplant Rejection by Microarray Analysis

Lande

Patil

Li³

et al. 2007

Proceedings of the American Thoracic Society

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Gene expression microarrays can estimate the prevalence of mRNA for thousands of genes in a small sample of cells or tissue. Organ transplant researchers are increasingly using microarrays to identify specific patterns of gene expression that predict and characterize acute and chronic rejection, and to improve our understanding of the mechanisms underlying organ allograft dysfunction. We used microarrays to assess gene expression in bronchoalveolar lavage cell samples from lung transplant recipients with and without acute rejection on simultaneous lung biopsies. These studies showed increased expression during acute rejection of genes involved in inflammation, apoptosis, and T-cell activation and proliferation. We also studied gene expression during the evolution of airway obliteration in a murine heterotopic tracheal transplant model of chronic rejection. These studies demonstrated specific patterns of gene expression at defined time points after transplantation in allografts, whereas gene expression in isografts reverted back to that of native tracheas within 2 wk after transplantation. These studies demonstrate the potential power of microarrays to identify biomarkers of acute and chronic lung rejection. The application of new genetic, genomic, and proteomic technologies is in its infancy, and the microarray-based studies described here are clearly only the beginning of their application to lung transplantation. The massive amount of data generated per tissue or cell sample has spawned an outpouring of invention in the bioinformatics field, which is developing methodologies to turn data into meaningful and reproducible clinical and mechanistic inferences. Keywords: allograft rejection; lung transplantation; microarrayLung and heart-lung transplants, introduced into clinical practice in 1981, have now been performed in over 20,000 individuals worldwide for whom effective medical therapy was not available (1). These procedures have been highly beneficial for many recipients, with 2-yr survival rates of approximately 70% and dramatic improvements in quality of life. Despite these remarkable successes, problems remain, and long-term survival rates for lung transplant recipients are considerably lower than those observed in kidney, heart, and liver recipients. This is due, in large part, to the development of chronic allograft rejection despite administration of immunosuppressive medications.

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Analysis of the Major Histocompatibility Complex in Graft Rejection Revisited by Gene Expression Profiles

Abstract: The study provides novel insights into the role of classical and non-classical MHC molecules in graft rejection.

Cited by 7 publications

References 28 publications

Prolonged ischemia increases severity of rejection in skin flap allotransplantation in rats

Prolonged ischemia increases severity of rejection in skin flap allotransplantation in rats

Influence of cytokine and intercellular adhesion molecule‐1 gene polymorphisms on acute rejection in pediatric renal transplantation

Novel Insights into Lung Transplant Rejection by Microarray Analysis

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