SINGLE NUCLEOTIDE POLYMORPHISMS (SNP) AND ASSOCIATION WITH RESISTANCE TO IMMUNE TOLERANCE INDUCTION

• US 20140286971A1
• Filed: 04/03/2014
• Published: 09/25/2014
• Est. Priority Date: 04/18/2008
• Status: Abandoned Application

• Current Assignee: University of Tennessee Research Foundation (University of Teesside)
• Original Assignee: University of Tennessee Research Foundation (University of Teesside)
• Inventors: Postlethwaite, Arnold E., Gu, Weikuan
• Application Number:
  US14/243,998
• Publication Number:
  US 20140286971A1
• Time in Patent Office: Days
• US Class Current: 424/184.1
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

This application discloses methods, systems and kits for correlating the presence or absence of certain nucleic acid sequences within a population with the ability to create immune tolerance in that same population. Tolerance can be induced by solo or repeated administration of antigen, including soluble antigens administered either intravenously or sublingually. This application also discloses methods for detecting variants. In addition the application addresses the use or avoidance of non steroidal anti inflammatory drugs in therapy.

Claims

1. A method for screening for susceptibility to immune tolerance development, comprising screening for at least one SNP.

2. A method of claim 1, wherein said method of screening comprises FISH.

3. The method of claim 1, wherein said method of screening comprises use of a DNA array.

4. The method of claim 1, wherein said method of screening comprises hybridizing a polynucleotide probe.

5. The method of claim 4, wherein said method is selected from the group consisting of:

allele-specific probe hybridization, allele-specific primer extension, allele-specific amplification, sequencing, 5′

nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis, and single-stranded conformation polymorphism.

6. The method of claim 1, wherein said method comprises correlating the presence or absence of the at least one SNP with ability of a host to develop immune tolerance as a result of administration of one or more antigens to the host.

7. The method of claim 6, wherein said host is a human.

8. The method of claim 6, wherein said at least one or more therapeutic agents comprises at least one antigen.

9. The method of claim 8, wherein said at least one antigen is a collagen.

10. The method of claim 8, wherein said collagen is selected from the group types consisting of:

I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII and XXVIII.

11. A method of screening for susceptibility of a host to immune tolerance development, said method comprising:

a. obtaining a sample from said host comprising nucleic acid;

b. isolating nucleic acid from said sample;

c. assaying said sample for the presence or absence of at least one SNP, wherein the presence or absence of the at least one SNP is indicative of an increased susceptibility to develop immune tolerance.

12. The method of claim 11, wherein said host is human.

13. The method of claim 11, wherein said sample is selected from the group comprising:

whole blood, blood plasma, urine, tears, semen, saliva, buccal mucosa, interstitial fluid, lymph fluid, meningeal fluid, amniotic fluid, glandular fluid, sputum, feces, perspiration, mucous, vaginal secretion, cerebrospinal fluid, hair, skin, fecal material, wound exudate, wound homogenate, and wound fluid.

14. The method of claim 11, wherein said immune tolerance is induced by administration of at least one antigen to the host.

15. The method of claim 14, wherein said at least one or more antigens is a collagen.

16. The method of claim 15, wherein said collagen is selected from the group types consisting of:

I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII and XXVIII.

17. The method of claim 11, wherein said immune tolerance developed is to a sclerotic disease.

18. The method of claim 17, wherein said sclerotic disease is systemic sclerosis.

19. The method of claim 11, wherein said method further comprises at least one computer program for use with at least one computer system, wherein said computer program includes a plurality of instructions comprising:

a. at least one instruction for aiding in identification of the presence or absence of said at least one SNP;

b. at least one instruction for associating the presence or absence of said at least one SNP with at least one disease state; and

c. at least one instruction for correlating the presence or absence of said at least one SNP with a score indicating susceptibility of a host to develop immune tolerance.

20. The method of claim 19, wherein said computer program further generates a report comprising the results of the plurality of instructions.

21. The method of claim 20, wherein said report is transmitted over a network.

22. The method of claim 20, wherein said report is transmitted through an on-line portal.

23. The method of claim 20, wherein said report is transmitted by paper or e-mail.

24. The method of claim 20, wherein said report is transmitted in a secure manner.

25. The method of claim 20, wherein said report is stored in a database.

26. A method of administering at least one therapeutic agent, the method comprising

a. genotyping one or more SNP(s) in the nucleic acid of a host,

b. correlating the one or more SNP(s) with one or more diseases or disorders,

c. using a mathematical algorithm to determine probability that said host will respond positively or negatively to administration of at least one therapeutic agent, and

d. administrating or not administrating a therapeutic agent to the host based on the results of said mathematical algorithm.

27. A method for conducting a clinical trial in which one or more antigen(s) are evaluated, said method comprising:

a. genotyping one or more SNP(s) relating to one or more diseases or disorders;

b. analyzing the genotyping results;

c. determining a course of action based on the results of said genotyping, wherein said course of action comprises

i. including individual in the clinical trial based on the results of said genotyping having indicated that said individuals are likely to respond to said one or more antigen(s), and/or

ii. excluding individuals from participating in the clinical trial based on the results of said genotyping having indicated that said individuals are not likely to respond to said one or more antigen(s).

28. A method for identifying an individual who has an altered risk for developing an autoimmune disease, comprising detecting a single nucleotide polymorphism (SNP) in SEQ ID NO:

1 in said individual'"'"'s nucleic acids, wherein the presence of the SNP is correlated with an altered risk for autoimmune disease.