Compositions and methods for diagnosing autoimmune aquaporinopathy
AssigneeThe Regents of the University of California
InventorsScott S. Zamvil, Sharon A. Sagan, Joseph J. Sabatino, Carson E. Moseley, Collin M. Spencer
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Abstract
Compositions, methods, and kits are provided for diagnosing autoimmune aquaporinopathy. In particular, cell-based assays are provided for detecting autoreactive T cells that bind to certain pathogenic T cell epitopes of aquaporins. The disclosed methods can be used for diagnosing aquaporinopathies, such as neuromyelitis optica spectrum disorder and Sjögren's syndrome.
Claims41
A method of detecting an autoreactive T cell associated with an autoimmune aquaporinopathy, the method comprising:
- a) contacting a population of CD4+ T cells with a natural antigen-presenting cell or an artificial antigen-presenting cell, wherein the natural antigen-presenting cell or the artificial antigen-presenting cell comprises a class II major histocompatibility complex of an I-Ab haplotype (MHC II I-Ab) presenting a peptide comprising a pathogenic T cell epitope of an aquaporin;
- and
- b) detecting binding of the autoreactive T cell, if present in the population of CD4+ T cells, to the pathogenic T cell epitope of the aquaporin or activation of the autoreactive T cell in response to the binding of the autoreactive T cell to the pathogenic T cell epitope of the aquaporin.
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A method of diagnosing and treating an autoimmune aquaporinopathy in a patient, the method comprising:
- a) obtaining a biological sample comprising a population of CD4+ T cells from the patient;
- b) contacting the population of CD4+ T cells with a natural antigen-presenting cell or an artificial antigen-presenting cell, wherein the natural antigen-presenting cell or the artificial antigen-presenting cell comprises a class II major histocompatibility complex of an I-Ab haplotype (MHC II I-Ab) presenting a peptide comprising a pathogenic T cell epitope of an aquaporin;
- c) detecting binding of the autoreactive T cell, if present in the population of CD4+ T cells, to the pathogenic T cell epitope of the aquaporin or activation of the autoreactive T cell in response to the binding of the autoreactive T cell to the pathogenic T cell epitope of the aquaporin, wherein said detecting the binding to the pathogenic T cell epitope or the activation of the autoreactive T cell in response to the binding of the autoreactive T cell to the pathogenic T cell epitope of the aquaporin indicates that the patient has the autoimmune aquaporinopathy;
- and
- d) treating the patient for the autoimmune aquaporinopathy if the patient is diagnosed as having the autoimmune aquaporinopathy based on said detecting the binding of the autoreactive T cell to the pathogenic T cell epitope of the aquaporin or the activation of the autoreactive T cell in response to the binding of the autoreactive T cell to the pathogenic T cell epitope of the aquaporin.
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An artificial antigen-presenting cell comprising a class II major histocompatibility complex of an I-Ab haplotype (MHC II I-Ab) bound to a peptide comprising a pathogenic T cell epitope of an aquaporin, wherein the peptide comprising the pathogenic T cell epitope is selected from:
- a peptide comprising or consisting of amino acids 133-149, 201-220, or 202-218 of aquaporin 4 (AQP4), wherein numbering of amino acid positions is relative to the reference amino acid sequence of SEQ ID NO:8;
- a peptide comprising or consisting of amino acids 174-190 of aquaporin 5 (AQP5), wherein numbering of amino acid positions is relative to the reference amino acid sequence of SEQ ID NO:9;
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- a peptide comprising or consisting of a sequence selected from the group consisting of SEQ ID NOS:
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A method of monitoring efficacy of a treatment of a patient for an autoimmune aquaporinopathy, the method comprising:
- obtaining a first biological sample comprising a first population of CD4+ T cells from the patient before the patient undergoes the treatment and a second biological sample comprising a second population of CD4+ T cells from the patient after the patient undergoes the treatment;
- contacting the first population of CD4+ T cells and the second population of CD4+ T cells with a natural antigen-presenting cell or an artificial antigen-presenting cell, wherein the natural antigen-presenting cell or the artificial antigen-presenting cell comprises a class II major histocompatibility complex of an I-Ab haplotype (MHC II I-Ab) presenting a peptide comprising a pathogenic T cell epitope of an aquaporin;
- measuring amounts of autoreactive T cells bound to the pathogenic T cell epitope of the aquaporin in the first population of CD4+ T cells and the second population of CD4+ T cells;
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- evaluating the efficacy of the treatment, wherein detection of increased amounts of the autoreactive T cells bound to the pathogenic T cell epitope of the aquaporin in the second population of CD4+ T cells compared to the first population of CD4+ T cells indicate that the patient is worsening or not responding to the treatment, and detection of decreased amounts of the autoreactive T cells bound to the pathogenic T cell epitope of the aquaporin in the second population of CD4+ T cells compared to the first population of CD4+ T cells indicate that the patient is improving;
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- altering the treatment if the patient is worsening or not responding to the treatment.
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Dependencies are inferred from the claim text.