Novel gene associated with rheumatoid arthritis
It is disclosed that novel polypeptides which has enhanced expression levels in the synovial tissues of human chronic rheumatoid arthritis (RA) patients compared with the synovial tissues of human osteoarthritis (OA) patients, polynucleotides encoding the polypeptides, vectors comprising the polynucleotides, transformant cells comprising the vectors and an antibody against the polypeptide. It is also disclosed that polynucleotides specifically hybridizing with the polynucleotides and having at least 15 nucleotides, a detection method which is useful for RA diagnosis, and a detection kit which is useful for RA diagnosis.
1 . (1) A polypeptide comprising an amino acid sequence represented by SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8 or SEQ ID NO:10 and having enhanced expression in chronic rheumatoid arthritis patients or
(2) a polypeptide comprising an amino acid sequence represented by SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8 or SEQ ID NO:10 in which 1 to 10 amino acids are substituted, deleted and/or inserted and having enhanced expression in chronic rheumatoid arthritis patients.
2 . A polypeptide consisting of an amino acid sequence represented by SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8 or SEQ ID NO:10.
3 . A polynucleotide encoding the polypeptide according to claim 1 or 2 .
4 . An expression vector comprising the polynucleotide according to claim 3 .
5 . A cell transformed with the expression vector according to claim 4 .
6 . A antibody which binds to a polypeptide comprising an amino acid sequence represented by SEQ ID NO:4 and having enhanced expression in chronic rheumatoid arthritis patients, a polypeptide comprising an amino acid sequence represented by SEQ ID NO:4 in which 1 to 10 amino acids are substituted, deleted and/or inserted and having enhanced expression in chronic rheumatoid arthritis patients or a polypeptide consisting of an amino acid sequence represented by SEQ ID NO:4.
7 . A polynucleotide which specifically hybridizes to a polynucleotide represented by SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7 or SEQ ID NO:9 and has at least 15 nucleotides.
8 . A method for detecting rheumatoid arthritis comprising
1) a step of assaying the expression level of a gene in a synovial biopsy sample of a test subject, said gene comprising
i) the nucleotide sequence according to claim 3 or
ii) a polynucleotide sequence encoding a polypeptide comprising an amino acid sequence represented by SEQ ID NO:12 and having enhanced expression in chronic rheumatoid arthritis patients, a polypeptide comprising an amino acid sequence represented by SEQ ID NO:12 in which 1 to 10 amino acids are substituted, deleted and/or inserted and having enhanced expression in chronic rheumatoid arthritis patients, or a polypeptide consisting of an amino acid sequence represented by SEQ ID NO:12; and
(2) a step of comparing the expression level of the gene with the expression levels thereof in a synovial biopsy sample in a normal subject or a patient with non-chronic rheumatoid arthritis.
9 . A kit for detecting chronic rheumatoid arthritis comprising forward and reverse primers designed for enabling specific amplification of a gene represented by
1) the polynucleotide according to claim 3 or
2) a polynucleotide encoding a polypeptide comprising an amino acid sequence represented by SEQ ID NO:12 and having enhanced expression in chronic rheumatoid arthritis patients, a polypeptide comprising an amino acid sequence represented by SEQ ID NO:12 in which 1 to 10 amino acids are substituted, deleted and/or inserted and having enhanced expression in chronic rheumatoid arthritis patients, or a polypeptide consisting of an amino acid sequence represented by SEQ ID NO:12.