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VITRO METHOD FOR THE PROGNOSIS OR PREDICTION OF THE RESPONSE IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH AGENTS THAT RECOGNIZE THE CD20 MEMBRANE RECEPTOR IN B LYMPHOCYTES

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اقرأ أكثر حفظ في قائمتي
  • Publication Date:
    September 6, 2012
  • معلومة اضافية
    • Document Number:
      20120225790
    • Appl. No:
      13/380665
    • Application Filed:
      June 09, 2010
    • نبذة مختصرة :
      An in vitro method for the prognosis or prediction of response in patients with rheumatoid arthritis to treatment with agents recognising the B-lymphocyte CD20 membrane receptor. The method of the invention comprises an assay in a blood sample from these patients and measuring, before starting the treatment, the transcriptional expression level (mRNA) of at least one of the genes selected from the group: ARG1, CPD, TRAF1, C1QA, LRRN3, HLA-DQA1, NLK, TLR4, LOC89944, TOM1L1, BACH, NCALD, EIF2C2, NFIC, PCDHB7, FLJ32770, ARID3A, C14ORF9, CSNK1E, BCAS1, TEAD2, C6orfl45 and SNTA1; and the comparison of this expression level to the expression values previously obtained in patients who responded and who did not respond to the treatment.
    • Inventors:
      Juliá Cano, Antonio (Barcelona, ES); Marsal Barril, Sara (Barcelona, ES)
    • Assignees:
      Fundacio Institut de Recerca de L'Hospital Universitari Vall D'Hebron (Barcelona, ES)
    • Claim:
      1. An in vitro method for the prognosis or prediction of the response to treatment with agents recognising the B-lymphocyte CD20 membrane receptor in patients with rheumatoid arthritis, comprising determining in a blood cell sample from these patients, the expression level of at least one, of any combination thereof or of all genes selected from the group: ARG1, CPD, TRAF1, C1QA, LRRN3, HLA-DQA1, NLK, TLR4, LOC89944, TOM1L1, BACH, NCALD, EIF2C2, NFIC, PCDHB7, FLJ32770, ARID3A, C14orf9, CSNK1E, BCAS1, TEAD2, C6orf145 and SNTA1; and comparing this expression level with the expression values obtained in patients responding to the treatment and those not responding to it.
    • Claim:
      2. An in vitro method according to claim 1, characterised in that the determination of the expression level of genes ARG1, CPD, TRAF1, C1QA, LRRN3, HLA-DQA1 and NLK is performed in whole blood samples.
    • Claim:
      3. A method according to claim 1, characterised in that the prognosis is performed according to the expression value obtained from the ARG1/TRAF1 ratio, without needing to compare the ratio value with the expression values obtained from patients responding to the treatment and those not responding to it, where a positive ARG1/TRAF1 ratio directly predicts that the patients will not respond to treatment and a negative ARG1/TRAF1 directly predicts that the patients will respond to treatment.
    • Claim:
      4. An in vitro method according to claim 1, characterised in that the determination of the expression level of genes TLR4, LOC89944, TOM1L1, BACH, NCALD, EIF2C2, NFIC, PCDHB7 and FLJ32770 is performed in CD4+T cells.
    • Claim:
      5. An in vitro method according to claim 1, characterised in that the determination of the expression level of genes ARID3A, C140RF9, CSNK1E, BCAS1, TEAD2, C6orf145 and SNTA1 is performed in B cells.
    • Claim:
      6. An in vitro method according to claim 1, comprising the determination of the expression level of the following set of genes: ARG1, TRAF1, TLR4 and ARID3A.
    • Claim:
      7. An in vitro method according to claim 1, characterised in that the genes TRAF1, LRRN3 and NLK are over-expressed in whole blood, the set of genes TLR4, TOM1L1, PCDHB7 and FLJ32770 are over-expressed in CD4+T cells and the set of genes C14ORF9, CSNK1E, BCAS1, TEAD2, C6orf145 and SNTA1 are over-expressed in B cells in responders before starting treatment.
    • Claim:
      8. An in vitro method according to claim 1, characterised in that the genes ARG1, CPD, C1QA and HLA-DQA1 are under-expressed in whole blood, the set of genes LOC89944, BACH, NCALD, EIF2C2 and NFIC is under-expressed in CD4+T cells and the ARID3A gene is under-expressed in B cells in patients responding before the start of treatment.
    • Claim:
      9. A method according to claim 1, characterised in that the gene expression level is determined by quantitation of mRNA levels in the blood cell sample.
    • Claim:
      10. An in vitro method according to claim 1, characterised in that the agent recognising the B-lymphocyte CD20 membrane receptor is rituximab.
    • Current U.S. Class:
      506/9
    • Current International Class:
      40; 12
    • الرقم المعرف:
      edspap.20120225790