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Methods of diagnosing rejection of a kidney allograft using genomic or proteomic expression profiling

A graft rejection, allogeneic technology, applied in the fields of biochemical equipment and methods, disease diagnosis, microbial determination/examination, etc., can solve the problem of not giving kidney transplant reviews and other issues

Inactive Publication Date: 2011-07-06
THE UNIV OF BRITISH COLUMBIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Neither Fiane nor Fildes gave comment on kidney transplants

Method used

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  • Methods of diagnosing rejection of a kidney allograft using genomic or proteomic expression profiling
  • Methods of diagnosing rejection of a kidney allograft using genomic or proteomic expression profiling
  • Methods of diagnosing rejection of a kidney allograft using genomic or proteomic expression profiling

Examples

Experimental program
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Effect test

preparation example Construction

[0109]For the preparation of monoclonal antibodies against biomarkers, any of the techniques provided for the production of antibody molecules can be used. Such techniques include, but are not limited to, hybridoma technology, triple hybridomas (e.g. Kohler and Milstein 1975, Nature 256:495-497; Gustafsson et al., 1991, Hum. Antibodies Hybridomas 2:26-32), human B- Cell hybridomas or EBV hybridomas eg (Kozbor et al., 1983, Immunology Today 4:72; Cole et al., 1985, in: Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Human or humanized 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., 1985, see: Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Techniques developed for the production of "chimeric antibodies" (Morrison et al., 1984, Proc. Natl. Acad. Sci. USA 81:6851-6855; Neu...

Embodiment approach

[0243] Nucleic acid profiling can also be used in combination with metabolite ("metabolomics") or proteomic profiling. Minor alterations in the subject's genome (eg, single nucleotide changes or polymorphisms) or genomic expression (eg, differential gene expression) may result in a rapid response 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 includes, for example, cholesterol, homocysteine, glucose, uric acid, malondialdehyde, and ketone bodies. Additional non-limiting examples of small molecule metabolites are listed in Table 3.

[0244] Table 3: Metabolites identified and quantified in NMR spectra of serum samples obtained from subject populations

[0245] Compound name ...

Embodiment 1

[0287] Example 1: Comparison of Biomarkers and Clinical Diagnosis

[0288] A total of 33 subjects were included in the study, including 11 patients with acute rejection within the first week post-transplant, and 22 patients without rejection for at least 6 months post-transplant. Thirty-three transplant patients were clinically stable 3 months after kidney transplantation. A total of 183 probe sets representing 160 genes were found to be statistically significant and consistently differentially expressed between AR and NR subjects (Table 2). exist Figure 10 The sequences represented by the probe sets are shown in . Samples from subjects with acute rejection within the first week post-transplant were clustered together and separated from samples from patients without rejection.

[0289] Using the set of nucleic acid markers listed in Table 5, the experimental subjects were classified into rejecters (AR) or non-rejectors (NR) ( Figure 1A -C).

[0290] In contrast, an inde...

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Abstract

A method of determining the acute allograft rejection status of a subject, the method comprising the steps of: determining the nucleic acid expression profile of one or more than one nucleic acid markers, or one or more than one proteomic markers in a biological sample from the subject; comparing the expression profile of the one or more than one nucleic acid markers to a control profile; and determining whether the expression level of the one or more than one nucleic acid markers is increased relative to the control profile, wherein the increase of the one or more than one nucleic acid markers is indicative of the acute rejection status of the subject.

Description

[0001] This application claims the benefit of priority to US Provisional Application 61 / 129,022, filed May 30, 2008, the contents of which are incorporated herein by reference. technical field [0002] The present invention relates to methods for diagnosing rejection of renal allografts using genomic expression profiling or 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 the survival and health of allograft recipients, it is important to identify allograft rejection as early and as precisely as possible And effective monitoring and adjustment of the dose of immunosuppressive drugs remains important for the continued survival of allograft recipients. [0004] Allograft rejection results from the recipient's immune response to nonself antigens expressed by the do...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68C40B30/00G01N33/483G01N33/53G01N33/543G01N33/68
CPCC12Q1/6883C12Q2600/158G01N2800/60C12Q2600/112G01N33/6842G01N2800/245C12Q2600/178Y10T436/143333G16B5/00
Inventor P·科欧文A·斯彻尔O·贡特尔R·巴尔肖R·恩格A·缪R·麦克马斯特B·麦克马纽斯G·科亨弗里尤A·梅里迪斯
Owner THE UNIV OF BRITISH COLUMBIA
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