Methods of diagnosing chronic cardiac allograft rejection

A graft rejection, allogeneic technique, applied in the field of diagnosing chronic cardiac allograft rejection, can solve the problems of little practicality, no success, difficult tissue evaluation, etc.

Inactive Publication Date: 2011-04-27
THE UNIV OF BRITISH COLUMBIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] Attempts have been made to reduce the number of biopsies and invasive surveillance techniques per patient, but have generally been unsuccessful, in part due to the difficulty of pinpointing the site of rejection initiation or progression, and also due to the difficulty of assessment organization
Non-invasive surveillance techniques have been investigated and may provide adequate negative predictions of allograft rejection, but may have less practical utility in the clinical setting (Mehra et al., supra)

Method used

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  • Methods of diagnosing chronic cardiac allograft rejection
  • Methods of diagnosing chronic cardiac allograft rejection
  • Methods of diagnosing chronic cardiac allograft rejection

Examples

Experimental program
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preparation example Construction

[0095] Regarding the preparation of monoclonal antibodies against biomarkers, any technique for the production of antibody molecules by continuous cell lines in culture can be used. Such techniques include, but are not limited to, the hybridoma technique originally developed by Kohler and Milstein (1975, Nature 256:495-497), the tripleoma technique (Gustafsson et al., 1991, Hum. Antibodies Hybridomas 2:26- 32), human B-cell hybridoma technology (Kozbor et al., 1983, Immunology Today 4:72) and EBV hybridoma technology for producing human monoclonal antibodies (Cole et al., 1985, see: Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Human antibodies can be used and can be obtained by using human hybridomas (Cote et al., 1983, Proc. Natl. Acad. Sci. USA 80:2026-2030) or by in vitro transformation of human B cells with EBV virus (Cole et al. et al., 1985, in: Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Techniques developed f...

Embodiment approach

[0202] T cell atlas of alloreactivity, metabolomics

[0203] T-cell profiling and / or metabolite ("metabolomics") profiling of alloreactivity can be used in combination with genomic and / or proteomic profiling. Small changes in the subject's genome (such as single base changes or polymorphisms) or small changes in genome expression (such as differential gene expression) may lead to rapid responses in the subject's small molecule metabolite profile. Small-molecule metabolites can also respond rapidly to environmental changes, with significant metabolite changes occurring within seconds to minutes of environmental change—conversely, changes in protein or gene expression may take hours or days to manifest. The list of clinical variables indicates several metabolites that can be used to monitor eg cardiovascular disease, obesity or metabolic syndrome - examples include cholesterol, homocysteine, glucose, uric acid, malondialdehyde and ketone bodies. Additional non-limiting examples...

Embodiment 1

[0252] After normalization and pre-screening, 25,215 probe sets remained and were included in the subsequent analysis using training cohort samples (step 2). Using robust testing, a total of 106 probe sets were identified with FDR Figure 4 ). In addition, overexpression analysis was performed to see the types of biological and molecular processes involved in differentially expressed genes and compared to other genes present on the microarray. Significantly enriched Gene Ontology (GO) terms were identified, those with p-values ​​< 0.05 have been summarized in Table 5.

[0253] Table 5. Statistically significant Gene Ontology terms identified by enrichment analysis of genomic expression profiles (FatiGo). P-value <0.05. The displayed GO terms (biological process and molecular function) are between GO levels 3 and 5.

[0254] process or response

Gene Ontology Terms (GO Terms)

immune response

GO: 0006955

response to biological stimuli

GO: 000...

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Abstract

The present invention relates to methods of diagnosing chronic rejection of a cardiac allograft using genomic expression profiling, proteomic expression profiling, or a combination of genomic and proteomic expression profiling.

Description

[0001] This application claims the benefit of priority of US Provisional Application 61 / 071,056, filed April 10, 2008, and US 61 / 157,166, filed March 3, 2009, both of which are incorporated herein by reference. technical field [0002] The present invention relates to methods for diagnosing chronic rejection of cardiac allografts using genomic expression profiling, proteomic expression profiling, or a combination of genomic and proteomic expression profiling. Background technique [0003] Transplantation is considered the mainstay of therapy for patients with organ failure at the end of life. Although the availability of immunosuppressants such as cyclosporine and tacrolimus has improved allograft recipient survival and health, it is important to identify allograft rejection and Effective monitoring and adjustment of the dose of immunosuppressive drugs remains important for the continued survival of allograft recipients. [0004] Rejection of an allograft is often described...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68C40B30/00C40B30/04G01N33/483G01N33/53G01N33/543G01N33/68
CPCG01N33/6848C12Q1/6883G01N33/6893C12Q2600/158G01N33/6842G01N2800/245G01N33/505G01N2800/32
Inventor B·麦克马努斯Z·霍兰德D·林R·巴尔肖R·麦克马斯特P·科欧文G·科赫恩弗罗伊J·威尔森-麦克马努斯R·恩格
Owner THE UNIV OF BRITISH COLUMBIA
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