Claims
- 1. A recombinant polynucleotide comprising a nucleotide sequence encoding a polypeptide epitope of at least 5 amino acids of Repro-EN-1.0 (SEQ ID NO:2), wherein the epitope specifically binds to antibodies from subjects diagnosed with endometriosis.
- 2. The polynucleotide of claim 1 wherein the nucleotide sequence is selected from the Repro-EN-1.0 sequence of SEQ ID NO:1.
- 3. The polynucleotide of claim 1 wherein the nucleotide sequence is a native Repro-EN-1.0 nucleotide sequence.
- 4. The polynucleotide of claim 1 wherein the nucleotide sequence is identical to nucleotides 176 to 2755 of SEQ ID NO:1.
- 5. The polynucleotide of claim 1 further comprising an expression control sequence operatively linked to the nucleotide sequence.
- 6. A recombinant polynucleotide comprising a nucleotide sequence encoding a polypeptide epitope of at least 5 amino acids of IB1 (SEQ ID NO:4), wherein the epitope specifically binds to antibodies from subjects diagnosed with endometriosis.
- 7. The polynucleotide of claim 6 wherein the nucleotide sequence is selected from the IB1 sequence of SEQ ID NO:3.
- 8. The polynucleotide of claim 6 wherein the nucleotide sequence is a native IB1 nucleotide sequence.
- 9. The polynucleotide of claim 6 wherein the nucleotide sequence is identical to nucleotides 176 to 2986 of SEQ ID NO:3.
- 10. The polynucleotide of claim 6 further comprising an expression control sequence operatively linked to the nucleotide sequence.
- 11. A polynucleotide primer pair which amplifies a nucleotide sequence encoding a polypeptide epitope of at least 5 amino acids of Repro-EN-1.0, wherein the epitope specifically binds to antibodies from subjects diagnosed with endometriosis, the pair comprising:
1) a 3′ primer of at least 7 nucleotides that specifically hybridizes to a 3′ end of the nucleotide sequence or downstream from the sequence, and 2) a 5′ primer of at least 7 nucleotides that specifically hybridizes to the 3′ end of the complement of the nucleotide sequence or downstream from the complement of the sequence.
- 12. The polynucleotide primer pair of claim 11 wherein the 3′ primer has a sequence complementary to a nucleotide sequence selected from Repro-EN-1.0 cDNA (SEQ ID NO:1), and the 5′ primer has a sequence identical to nucleotide sequence selected from Repro-EN-1.0 cDNA (SEQ ID NO:1).
- 13. The polynucleotide primer pair of claim 11 wherein the pair of polynucleotides are peptide nucleic acids.
- 14. A polynucleotide primer pair which amplifies a nucleotide sequence encoding a polypeptide epitope of at least 5 amino acids of IB1, wherein the epitope specifically binds to antibodies from subjects diagnosed with endometriosis, the pair comprising:
1) a 3′ primer of at least 7 nucleotides that specifically hybridizes to a 3′ end of the nucleotide sequence or downstream from the sequence, and 2) a 5′ primer of at least 7 nucleotides that specifically hybridizes to the 3′ end of the complement of the nucleotide sequence or downstream from the complement of the sequence.
- 15. The polynucleotide primer pair of claim 14 wherein the 3′ primer has a sequence complementary to a nucleotide sequence selected from IB1 cDNA (SEQ ID NO:3), and the 5′ primer has a sequence identical to nucleotide sequence selected from IB1 cDNA (SEQ ID NO:3).
- 16. The polynucleotide primer pair of claim 14 wherein the pair of polynucleotides are peptide nucleic acids.
- 17. A recombinant cell comprising a recombinant polynucleotide comprising an expression control sequence operatively linked to a nucleotide sequence encoding a polypeptide epitope of at least 5 amino acids of Repro-EN-1.0 (SEQ ID NO:2), wherein the epitope specifically binds to antibodies from subjects diagnosed with endometriosis.
- 18. A method for detecting a target polynucleotide comprising a nucleotide sequence selected from Repro-EN-1.0 cDNA (SEQ ID NO:1) or its complement in a sample comprising the steps of:
(a) contacting the sample with a polynucleotide probe or primer comprising a sequence of at least 7 nucleotides that specifically hybridizes to the nucleotide sequence and (b) detecting whether the probe or primer has specifically hybridized to the target polynucleotide, whereby specific hybridization provides a detection of the target polynucleotide in the sample.
- 19. The method of claim 18 wherein the polynucleotide probe or primer is a peptide nucleic acid.
- 20. A recombinant cell comprising a recombinant polynucleotide comprising an expression control sequence operatively linked to a nucleotide sequence encoding a polypeptide epitope of at least 5 amino acids of IB1 (SEQ ID NO:4), wherein the epitope specifically binds to antibodies from subjects diagnosed with endometriosis.
- 21. A method for detecting a target polynucleotide comprising a nucleotide sequence selected from IB1 cDNA (SEQ ID NO:3) or its complement in a sample comprising the steps of:
(a) contacting the sample with a polynucleotide probe or primer comprising a sequence of at least 7 nucleotides that specifically hybridizes to the nucleotide sequence and (b) detecting whether the probe or primer has specifically hybridized to the target polynucleotide, whereby specific hybridization provides a detection of the target polynucleotide in the sample.
- 22. The method of claim 21 wherein the polynucleotide probe or primer is a peptide nucleic acid.
- 23. A purified, recombinant Repro-EN-1.0 polypeptide whose amino acid sequence is identical to that of SEQ ID NO:2, or an allelic variant of SEQ ID NO:2.
- 24. A purified, recombinant IB1 polypeptide whose amino acid sequence is identical to that of SEQ ID NO:4, or an allelic variant of SEQ ID NO:4.
- 25. A purified polypeptide comprising an epitope of at least 5 amino acids of Repro-EN-1.0 (SEQ ID NO:2), wherein the epitope specifically binds to antibodies from subjects diagnosed with endometriosis.
- 26. A purified polypeptide comprising an epitope of at least 5 amino acids of IB1 (SEQ ID NO:4), wherein the epitope specifically binds to antibodies from subjects diagnosed with endometriosis.
- 27. A composition consisting essentially of an antibody that specifically binds to Repro-EN-1.0 polypeptide (SEQ ID NO:2).
- 28. The composition of claim 27 wherein the antibodies are monoclonal antibodies.
- 29. A composition consisting essentially of an antibody that specifically binds to IB1 polypeptide (SEQ ID NO:4).
- 30. The composition of claim 27 wherein the antibodies are monoclonal antibodies.
- 31. A method for detecting a Repro-EN-1.0 polypeptide in a sample, comprising the steps of:
(a) contacting the sample with an antibody that specifically binds to the Repro-EN-1.0 polypeptide and (b) detecting specific binding between the antibody and Repro-EN-1.0 polypeptide, whereby specific binding provides a detection of Repro-EN-1.0 polypeptide in the sample.
- 32. A method for detecting a IB1 polypeptide in a sample, comprising the steps of:
(a) contacting the sample with an antibody that specifically binds to the IB1 polypeptide and (b) detecting specific binding between the antibody and IB1 polypeptide, whereby specific binding provides a detection of IB1 polypeptide in the sample.
- 33. A method for diagnosing endometriosis in a subject comprising the steps of:
(a) detecting a test amount of an antibody that specifically binds to Repro-EN-1.0 polypeptide in a sample from the subject; and (b) comparing the test amount with a normal range of the antibody in a control sample from a subject who does not suffer from endometriosis, whereby a test amount above the normal range provides a positive indication in the diagnosis of endometriosis.
- 34. The method of claim 33 wherein the sample comprises blood serum.
- 35. The method of claim 33 wherein the antibody is an IgE immunoglobulin.
- 36. The method of claim 33 wherein the antibody is an IgG immunoglobulin.
- 37. The method of claim 33 wherein the antibody is an IgG4 immunoglobulin.
- 38. The method of claim 33 wherein the step of detecting comprises capturing the antibody from the sample with an immobilized Repro-EN-1.0 or a peptide comprising an epitope of Repro-EN-1.0 and detecting captured antibody.
- 39. The method of claim 33 wherein the step of detecting comprises capturing the antibody from the sample with an immobilized anti-immunoglobulin antibody and detecting captured antibody.
- 40. The method of claim 38 wherein the step of detecting captured antibody comprises contacting the captured antibody with a detectable antibody that specifically binds immunoglobulins and detecting binding between the captured antibody and the detectable antibody.
- 41. The method of claim 39 wherein the step of detecting captured antibody comprises contacting the captured antibody with Repro-EN-1.0 or a polypeptide comprising an epitope of Repro-EN-1.0 and detecting binding between the captured antibody and the Repro-EN-1.0 or polypeptide.
- 42. A method for diagnosing endometriosis in a subject comprising the steps of:
(a) detecting a test amount of an antibody that specifically binds to IB1 polypeptide in a sample from the subject; and (b) comparing the test amount with a normal range of the antibody in a control sample from a subject who does not suffer from endometriosis, whereby a test amount above the normal range provides a positive indication in the diagnosis of endometriosis.
- 43. The method of claim 42 wherein the sample comprises blood serum.
- 44. The method of claim 42 wherein the antibody is an IgE immunoglobulin.
- 45. The method of claim 42 wherein the antibody is an IgG immunoglobulin.
- 46. The method of claim 42 wherein the antibody is an IgG4 immunoglobulin.
- 47. The method of claim 42 wherein the step of detecting comprises capturing the antibody from the sample with an immobilized IB1 or a peptide comprising an epitope of IB1 and detecting captured antibody.
- 48. The method of claim 46 wherein the step of detecting comprises capturing the antibody from the sample with an immobilized anti-immunoglobulin antibody and detecting captured antibody.
- 49. The method of claim 47 wherein the step of detecting captured antibody comprises contacting the captured antibody with a detectable antibody that specifically binds immunoglobulins and detecting binding between the captured antibody and the detectable antibody.
- 50. The method of claim 48 wherein the step of detecting captured antibody comprises contacting the captured antibody with IB1 or a polypeptide comprising an epitope of IB1 and detecting binding between the captured antibody and the IB1 or polypeptide.
- 51. A method for use in following the progress of endometriosis in a subject comprising the steps of:
(a) detecting first and second amounts of an antibody that specifically binds Repro-EN-1.0 polypeptide in samples from the subject at a first and a second time, respectively; and (b) comparing the first and second amounts, whereby an increase between the first and second amounts indicates progression of the endometriosis and a decrease between the first and second amounts indicates remission of the endometriosis.
- 52. A method for use in following the progress of endometriosis in a subject comprising the steps of:
(a) detecting first and second amounts of an antibody that specifically binds IB1 polypeptide in samples from the subject at a first and a second time, respectively; and (b) comparing the first and second amounts, whereby an increase between the first and second amounts indicates progression of the endometriosis and a decrease between the first and second amounts indicates remission of the endometriosis.
- 53. An isolated MHC-peptide complex comprising:
at least a portion of an MHC Class I molecule or an MHC Class II molecule, wherein the portion comprises a binding site that specifically binds a peptide having an amino acid binding motif specific to the molecule, and wherein the portion engages in CD4-mediated or CD8-mediated binding to T cells, and a peptide of at least 8 amino acids in a sequence selected from the amino acid sequence of Repro-EN-1.0 (SEQ ID NO:2), wherein the peptide comprises the amino acid binding motif and comprises an epitope that specifically binds to a T cell receptor; wherein the complex specifically binds a T cell having a T cell receptor that specifically binds to the epitope, and wherein specific binding induces anergy in the T cell.
- 54. An isolated MHC-peptide complex comprising:
at least a portion of an MHC Class I molecule or an MHC Class II molecule, wherein the portion comprises a binding site that specifically binds a peptide having an amino acid binding motif specific to the molecule, and wherein the portion engages in CD4-mediated or CD8-mediated binding to T cells, and a peptide of at least 8 amino acids in a sequence selected from the amino acid sequence of IB1 (SEQ ID NO:4), wherein the peptide comprises the amino acid binding motif and comprises an epitope that specifically binds to a T cell receptor; wherein the complex specifically binds a T cell having a T cell receptor that specifically binds to the epitope, and wherein specific binding induces anergy in the T cell.
- 55. A method for treating endometriosis in a subject comprising the step of inhibiting an immune response against Repro-EN-1.0 in the subject.
- 56. The method of claim 55 comprising administering to the subject an immunosuppressant in an amount effective to inhibit the immune response.
- 57. The method of claim 55 comprising administering to the subject an isolated MHC-peptide complex of claim 54 in an amount effective to inhibit the immune response.
- 58. The method of claim 55 comprising administering to the subject an anti-idiotypic antibody that specifically binds to an antigen binding site of an antibody that specifically binds to Repro-EN-1.0 in an amount effective to inhibit the immune response.
- 59. A method for treating endometriosis in a subject comprising the step of inhibiting an immune response against IB1 in the subject.
- 60. The method of claim 59 comprising administering to the subject an immunosuppressant in an amount effective to inhibit the immune response.
- 61. The method of claim 59 comprising administering to the subject an isolated MHC-peptide complex of claim 58 in an amount effective to inhibit the immune response.
- 62. The method of claim 59 comprising administering to the subject an anti-idiotypic antibody that specifically binds to an antigen binding site of an antibody that specifically binds to IB1 in an amount effective to inhibit the immune response.
- 63. A screening method for determining whether a compound increases or decreases the expression of Repro-EN-1.0 in a cell comprising contacting the cell with the compound and determining whether the production of Repro-EN-1.0 mRNA or polypeptide are increased or decreased.
- 64. A screening method for determining whether a compound increases or decreases the expression of IB1 in a cell comprising contacting the cell with the compound and determining whether the production of IB1 mRNA or polypeptide are increased or decreased.
- 65. A method of detecting a chromosomal translocation of a Repro-EN-1.0 gene comprising the steps of:
a) hybridizing a labeled polynucleotide probe that specifically hybridizes with the Repro-EN-1.0 nucleotide sequence of SEQ ID NO:1 or its complement, to a chromosome spread from a cell sample to determine the pattern of hybridization and b) determining whether the pattern of hybridization differs from a normal pattern; whereby a difference in the pattern represents a translocation.
- 66. A method of detecting a chromosomal translocation of a IB1 gene comprising the steps of:
a) hybridizing a labeled polynucleotide probe that specifically hybridizes with the IB1 nucleotide sequence of SEQ ID NO:3 or its complement, to a chromosome spread from a cell sample to determine the pattern of hybridization and b) determining whether the pattern of hybridization differs from a normal pattern; whereby a difference in the pattern represents a translocation.
- 67. A method of detecting polymorphic forms of Repro-EN-1.0 comprising the steps of:
a) determining the identity of a nucleotide or amino acid at a selected position within the sequence of a test Repro-EN-1.0 gene or polypeptide; b) determining the identity of the nucleotide or amino acid at the corresponding position of native Repro-EN-1.0 (SEQ ID NO:1 or 2) gene or polypeptide; and c) comparing the identity from the test gene or polynucleotide with the identity of the native gene or polypeptide, whereby a difference in identity indicates that the test polynucleotide is a polymorphic form of Repro-EN-1.0.
- 68. A method of detecting polymorphic forms of IB1 comprising the steps of:
a) determining the identity of a nucleotide or amino acid at a selected position within the sequence of a test IB1 gene or polypeptide; b) determining the identity of the nucleotide or amino acid at the corresponding position of native IB1 (SEQ ID NO:3 or 4) gene or polypeptide; and c) comparing the identity from the test gene or polynucleotide with the identity of the native gene or polypeptide, whereby a difference in identity indicates that the test polynucleotide is a polymorphic form of IB1.
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is related to co-pending application of Schneider et al., “Diagnosis Of Autoimmune Disease By Detecting IgE or IgG4 Autoantibodies Against Autoantigens,” attorney docket no. 018002-001200, filed on even date herewith, the content of which is incorporated herein by reference in its entirety.
[0002] This application is a continuation in part of U.S. patent application Ser. No. 09/359,084 filed Jul. 22, 1999, which, in turn, is a continuation of Provisional Patent Application Serial No. 60/094,930, filed Jul. 31, 1998.
FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0003] Certain work described herein was supported by SBIR grant no. 1R43 HD 33022-01A2 between the United States Department of Health and Human Services and Reprogen, Inc. The Government may have certain rights in this invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60094930 |
Jul 1998 |
US |
Divisions (1)
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Number |
Date |
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Parent |
09447399 |
Nov 1999 |
US |
Child |
10172573 |
Jun 2002 |
US |
Continuation in Parts (1)
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Number |
Date |
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Parent |
09359084 |
Jul 1999 |
US |
Child |
09447399 |
Nov 1999 |
US |