Diagnosis of autoimmune disease
Methods and compositions for diagnosing and treating autoimmune disease, e.g., acute disseminated encephalomyelitis (ADEM), are described.
1. A method of detecting the presence of autoantibodies to myelin oligodendrocyte glycoprotein (MOG) in a subject, the method comprising:
obtaining a sample comprising serum or CSF from the subject;
contacting the sample with a multimeric polypeptide, wherein the multimeric polypeptide comprises two or more fusion polypeptides comprising
(i) a first portion comprising an antigenic extracellular domain of MOG comprising the sequence RISPGKNATGMEVGWYRS (SEQ ID NO:24); and
(ii) a second portion comprising a multimerizing domain linked to the first portion, optionally via a linker,
under conditions that allow binding of the multimeric polypeptide to antibodies present in the sample, if any, to thereby form multimeric polypeptide/antibody complexes; and
detecting the presence of said multimeric polypeptide/antibody complexes in the sample, wherein the presence of multimeric polypeptide/antibody complexes in the sample indicates the presence of autoantibodies to MOG in the subject.
2. The method of claim 1 , further comprising selecting or rejecting the subject for inclusion in a clinical trial based upon the presence or absence of MOG autoantibodies in the sample.
3. A method of detecting the presence of antibodies to myelin oligodendrocyte glycoprotein (MOG) in a sample, the method comprising:
contacting the sample with a tetrameric polypeptide,
wherein the tetrameric polypeptide comprises four fusion polypeptides comprising
(i) a first portion comprising an antigenic extracellular domain of MOG comprising the sequence RISPGKNATGMEVGWYRS (SEQ ID NO:24); and
(ii) a second portion comprising a multimerizing domain linked to the first portion, optionally via a linker,
under conditions that allow binding of the tetrameric polypeptide to antibodies present in the sample, if any, to form tetrameric polypeptide/antibody complexes; and
detecting the presence of tetrameric polypeptide/antibody complexes in the sample, thereby detecting the presence of the antibody in the sample.
4. The method of claim 1 , wherein the multimerizing domain comprises streptavidin.
5. The method of claim 1 , wherein the multimeric polypeptide further comprises a linker.
6. The method of claim 1 , wherein the multimeric polypeptide is a tetramer.
7. The method of claim 3 , wherein the multimerizing domain comprises streptavidin.
8. The method of claim 3 , wherein the multimeric polypeptide further comprises a linker.
9. A method of detecting the presence of autoantibodies to myelin oligodendrocyte glycoprotein (MOG) in a subject, the method comprising:
obtaining a sample comprising serum or CSF from the subject;
contacting the sample with a multimeric polypeptide, wherein the multimeric polypeptide comprises two or more fusion polypeptides comprising
(i) a first portion comprising an antigenic extracellular domain of MOG comprising amino acids 27-146 of SEQ ID NO:2; and
(ii) a second portion comprising a multimerizing domain linked to the first portion, optionally via a linker,
under conditions that allow binding of the multimeric polypeptide to antibodies present in the sample, if any, to thereby form multimeric polypeptide/antibody complexes; and
detecting the presence of said multimeric polypeptide/antibody complexes in the sample, wherein the presence of multimeric polypeptide/antibody complexes in the sample indicates the presence of autoantibodies to MOG in the subject.
10. A method of detecting the presence of antibodies to myelin oligodendrocyte glycoprotein (MOG) in a sample, the method comprising:
contacting the sample with a tetrameric polypeptide,
wherein the tetrameric polypeptide comprises four fusion polypeptides comprising
(i) a first portion comprising an antigenic extracellular domain of MOG comprising amino acids 27-146 of SEQ ID NO: 2; and
(ii) a second portion comprising a multimerizing domain linked to the first portion, optionally via a linker,
under conditions that allow binding of the tetrameric polypeptide to antibodies present in the sample, if any, to form tetrameric polypeptide/antibody complexes; and
detecting the presence of tetrameric polypeptide/antibody complexes in the sample,
thereby detecting the presence of the antibody in the sample.
11. The method of claim 9 , wherein the multimerizing domain comprises streptavidin.
12. The method of claim 9 , wherein the multimeric polypeptide further comprises a linker.
13. The method of claim 9 , wherein the multimeric polypeptide is a tetramer.
14. The method of claim 10 , wherein the multimerizing domain comprises streptavidin.
15. The method of claim 10 , wherein the multimeric polypeptide further comprises a linker.