Polynucleotide encoding autoantigens associated with endometriosis
AssigneeSiemens Medical Solutions Diagnostics
InventorsA. Said El Shami, Surendra Nath Menon, Cynthia K. French
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Abstract
This invention provides a polynucleotide encoding Repro-EN-1.0 and IB1, polypeptides associated with endometriosis. Auto-antibodies against Repro-EN-1.0 and IB1 have been found in subjects diagnosed with endometriosis. This invention also provides methods of using this polynucleotide and polypeptide.
Claims68
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
A composition consisting essentially of an antibody that specifically binds to Repro-EN-1.0 polypeptide (SEQ ID NO:2).
A composition consisting essentially of an antibody that specifically binds to IB1 polypeptide (SEQ ID NO:4).
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.
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.
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.
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.
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.
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.
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.
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.
A method for treating endometriosis in a subject comprising the step of inhibiting an immune response against Repro-EN-1.0 in the subject.
A method for treating endometriosis in a subject comprising the step of inhibiting an immune response against IB1 in the subject.
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.
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.
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.
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.
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.
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.
Dependencies are inferred from the claim text.