Methods and compositions for diagnosing or monitoring auto immune and chronic inflammatory diseases

• US 20040009479A1
• Filed: 04/24/2002
• Published: 01/15/2004
• Est. Priority Date: 06/08/2001
• Status: Active Grant

• Current Assignee: CareDx, Inc.
• Original Assignee: Expression Diagnostics, Inc.
• Inventors: Woodward, Robert, Ly, Ngoc, Wohlgemuth, Jay, Fry, Kirk
• Granted Patent: US 6,905,827 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Methods of diagnosing or monitoring an autoimmune or chronic inflammatory disease, particularly SLE in a patient by detecting the expression level of one or more genes or surrogates derived therefrom in the patient are described. Diagnostic oligonucleotides for diagnosing or monitoring chronic inflammatory disease, particularly SLE infection and kits or systems containing the same are also described.

Claims

1. A method of diagnosing or monitoring an autoimmune or chronic inflammatory disease in a patient, comprising detecting the expression level of one or more genes or surrogates derived therefrom in said patient to diagnose or monitor said autoimmune or chronic inflammatory disease in said patient wherein said genes comprise a nucleotide sequence selected from the group consisting of SEQ ID NO:

41;

SEQ ID NO;

328;

SEQ ID NO;

668;

SEQ ID NO;

855;

SEQ ID NO;

981;

SEQ ID NO;

1001;

SEQ ID NO;

1003;

SEQ ID NO;

1025;

SEQ ID NO;

1035;

SEQ ID NO;

1227;

SEQ ID NO;

1341;

SEQ ID NO;

1390;

SEQ ID NO;

1436;

SEQ ID NO;

1535;

SEQ ID NO;

1750;

SEQ ID NO;

2102;

SEQ ID NO;

2331;

SEQ ID NO;

2386;

SEQ ID NO;

2412;

SEQ ID NO;

2560;

SEQ ID NO;

2648;

SEQ ID NO;

2895, SEQ ID NO;

3249;

SEQ ID NO;

3305;

SEQ ID NO;

3541;

SEQ ID NO;

3692;

SEQ ID NO;

3701;

SEQ ID NO;

3741;

SEQ ID NO;

3825;

SEQ ID NO;

3827;

SEQ ID NO;

3832;

SEQ ID NO;

4149;

SEQ ID NO;

4400;

SEQ ID NO;

4601;

SEQ ID NO;

4604;

SEQ ID NO;

4631;

SEQ ID NO;

4637;

SEQ ID NO;

5067;

SEQ ID NO;

5074;

SEQ ID NO;

5468;

SEQ ID NO;

5531;

SEQ ID NO;

5607;

SEQ ID NO;

6382;

SEQ ID NO;

6956;

SEQ ID NO;

7238;

SEQ ID NO;

7330;

SEQ ID NO;

7641;

SEQ ID NO;

8015 and SEQ ID NO;

8095.

2. The method of claim 1 wherein said chronic inflammatory disease is systemic lupus erythematosis (SLE).

3. The method of claim 1 wherein said expression level is detecting by measuring the RNA level expressed by said gene.

4. The method of claim 3 further including isolating RNA from said patient prior to detecting the RNA level expressed by said gene.

5. The method of claim 4 wherein said RNA level is detected by PCR.

6. The method of claim 4 wherein said RNA level is detected by hybridization.

7. The method of claim 4 wherein said RNA level is detected by hybridization to an oligonucleotide.

8. The method of claim 7 wherein said oligonucleotide has a nucleotide sequence consisting of SEQ ID NO:

4637.

9. The method of claim 8 wherein the nucleotide sequence comprises DNA, RNA, cDNA, PNA, genomic DNA, or synthetic oligonucleotides.

10. The method of claim 1 wherein said expression is detecting by measuring protein levels of said gene.

11. A diagnostic oligonucleotide for diagnosing or monitoring an autoimmune or chronic inflammatory disease in a patient wherein the oligonucleotide comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:

41;

SEQ ID NO;

328;

SEQ ID NO;

668;

SEQ ID NO;

855;

SEQ ID NO;

981;

SEQ ID NO;

1001;

SEQ ID NO;

1003;

SEQ ID NO;

1025;

SEQ ID NO;

1035;

SEQ ID NO;

1227;

SEQ ID NO;

1341;

SEQ ID NO;

1390;

SEQ ID NO;

1436;

SEQ ID NO;

1535;

SEQ ID NO;

1750;

SEQ ID NO;

2102;

SEQ ID NO;

2331;

SEQ ID NO;

2386;

SEQ ID NO;

2412;

SEQ ID NO;

2560;

SEQ ID NO;

2648;

SEQ ID NO;

2895, SEQ ID NO;

3249;

SEQ ID NO;

3305;

SEQ ID NO;

3541;

SEQ ID NO;

3692;

SEQ ID NO;

3701;

SEQ ID NO;

3741;

SEQ ID NO;

3825;

SEQ ID NO;

3827;

SEQ ID NO;

3832;

SEQ ID NO;

4149;

SEQ ID NO;

4400;

SEQ ID NO;

4601;

SEQ ID NO;

4604;

SEQ ID NO;

4631;

SEQ ID NO;

4637;

SEQ ID NO;

5067;

SEQ ID NO;

5074;

SEQ ID NO;

5468;

SEQ ID NO;

5531;

SEQ ID NO;

5607;

SEQ ID NO;

6382;

SEQ ID NO;

6956;

SEQ ID NO;

7238;

SEQ ID NO;

7330;

SEQ ID NO;

7641;

SEQ ID NO;

8015 and SEQ ID NO;

8095.

12. The diagnostic oligonucleotide of claim 111, wherein said chronic inflammatory disease is systemic lupus erythematosis (SLE).

13. The diagnostic oligonucleotide of claim 12, wherein the nucleotide sequence comprises DNA, cDNA, PNA, genomic DNA, or synthetic oligonucleotides.

14. A system or kit for diagnosing or monitoring chronic inflammatory disease in a patient comprising an isolated nucleic acid wherein said isolated nucleic acid detects the expression level of a gene wherein said gene comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:

41;

SEQ ID NO;

328;

SEQ ID NO;

668;

SEQ ID NO;

855;

SEQ ID NO;

981;

SEQ ID NO;

1001;

SEQ ID NO;

1003;

SEQ ID NO;

1025;

SEQ ID NO;

1035;

SEQ ID NO;

1227;

SEQ ID NO;

1341;

SEQ ID NO;

1390;

SEQ ID NO;

1436;

SEQ ID NO;

1535;

SEQ ID NO;

1750;

SEQ ID NO;

2102;

SEQ ID NO;

2331;

SEQ ID NO;

2386;

SEQ ID NO;

2412;

SEQ ID NO;

2560;

SEQ ID NO;

2648;

SEQ ID NO;

2895, SEQ ID NO;

3249;

SEQ ID NO;

3305;

SEQ ID NO;

3541;

SEQ ID NO;

3692;

SEQ ID NO;

3701;

SEQ ID NO;

3741;

SEQ ID NO;

3825;

SEQ ID NO;

3827;

SEQ ID NO;

3832;

SEQ ID NO;

4149;

SEQ ID NO;

4400;

SEQ ID NO;

4601;

SEQ ID NO;

4604;

SEQ ID NO;

4631;

SEQ ID NO;

4637;

SEQ ID NO;

5067;

SEQ ID NO;

5074;

SEQ ID NO;

5468;

SEQ ID NO;

5531;

SEQ ID NO;

5607;

SEQ ID NO;

6382;

SEQ ID NO;

6956;

SEQ ID NO;

7238;

SEQ ID NO;

7330;

SEQ ID NO;

7641;

SEQ ID NO;

8015 and SEQ ID NO;

8095.

15. The kit of claim 14 wherein said chronic inflammatory disease is systemic lupus erythematosis (SLE).

16. The system of claim 14 wherein the nucleic acid is synthetic DNA, genomic DNA, RNA, PNA or cDNA.

17. The system of claim 14 wherein the isolated DNA molecule is immobilized on an array.

18. The system of claim 17 wherein the array is selected from the group consisting of a chip array, a plate array, a bead array, a pin array, a membrane array, a solid surface array, a liquid array, an oligonucleotide array, polynucleotide array or a cDNA array, a microtiter plate, a membrane and a chip.

19. The system of claim 14 wherein and said isolated nucleic acid is at least 14 nucleotides in length.