Genes and genes combinations predictive of early response or non response of subjects suffering from inflammatory disease to cytokine targeting drugs (cytd)

A kit for the in vitro diagnosis of a CyTD responding or non responding phenotype, comprising at least one reagent for the determination of an expression profile comprising or consisting of:

• (i) the gene MAPK14;
• or the genes MAPK14 and S100A9;
• or the genes MAPK14 and GNLY;
• or the 61 genes of Table 2,
• (ii) the gene S100A9;
• or the genes S100A9, IL2RB, and CASP5;
• or the genes S100A9, IL2RB, KLRK1, HCK, and GNLY;
• or the genes S100A9, IL2RB, KLRK1, HCK, GNLY, CTSZ, ARF5, and UTP14C, or
• (iii) Equivalent Expression Profile of anyone of the expression profiles of (i) and (ii),
• and optionally one or more housekeeping gene(s).

A nucleic acid microarray comprising nucleic acids specific for:

• (i) the gene MAPK14;
• or the genes MAPK14 and S100A9;
• or the genes MAPK14 and GNLY;
• or the 61 genes of Table 2,
• (ii) the gene S100A9;
• or the genes S100A9, IL2RB, and CASP5;
• or the genes S100A9, IL2RB, KLRK1, HCK, and GNLY;
• or the genes S100A9, IL2RB, KLRK1, HCK, GNLY, CTSZ, ARF5, and UTP14C, or
• (iii) Equivalent Expression Profile of anyone of the expression profiles of (i) and (ii),
• and optionally one or more housekeeping gene(s).

A method for designing a CyTD treatment for a subject suffering from an inflammatory disease, said method comprising:

• (a) determining from a biological sample of said subject an expression profile comprising or consisting of:
• (i) the gene MAPK14;
• or the genes MAPK14 and S100A9;
• or the genes MAPK14 and GNLY;
• or the 61 genes of Table 2,
• (ii) the gene S100A9;
• or the genes S100A9, IL2RB, and CASP5;
• or the genes S100A9, IL2RB, KLRK1, HCK, and GNLY;
• or the genes S100A9, IL2RB, KLRK1, HCK, GNLY, CTSZ, ARF5, and UTP14C, or
• (iii) Equivalent Expression Profile of anyone of the expression profiles of (i) and (ii),
• and optionally one or more housekeeping gene(s)
• (b) comparing the obtained expression profile with at least one reference expression profile,
• (c) determining the responding or non-responding phenotype of said subject from said comparison, and
• (d) designing a dose of CyTD treatment according to the said identified responding or non-responding phenotype.

A method for adapting the CyTD treatment of a subject suffering from an inflammatory disease, said method comprising:

• (a) determining from a biological sample of said subject an expression profile comprising or consisting of:
• (i) the gene MAPK14;
• or the genes MAPK14 and S100A9;
• or the genes MAPK14 and GNLY;
• or the 61 genes of Table 2,
• (ii) the gene S100A9;
• or the genes S100A9, IL2RB, and CASP5;
• or the genes S100A9, IL2RB, KLRK1, HCK, and GNLY;
• or the genes S100A9, IL2RB, KLRK1, HCK, GNLY, CTSZ, ARF5, and UTP14C, or
• (iii) Equivalent Expression Profile of anyone of the expression profiles of (i) and (ii),
• and optionally one or more housekeeping gene(s),
• (b) comparing the obtained expression profile with at least one reference expression profile,
• (c) determining the responding or non-responding phenotype of said subject from said comparison, and
• (d) adapting the CyTD treatment.

A method of treatment of an RA-suffering subject, comprising the steps of:

• (a) administering a therapeutic dose of a disease-modifying anti-rheumatic drug (DMARD) to the said subject suffering from RA,
• (b) determining from a biological sample of a RA-suffering subject an expression profile comprising or consisting of:
• (i) the gene MAPK14;
• or the genes MAPK14 and S100A9;
• or the genes MAPK14 and GNLY;
• or the 61 genes of Table 2,
• (ii) the gene S100A9;
• or the genes S100A9, IL2RB, and CASP5;
• or the genes S100A9, IL2RB, KLRK1, HCK, and GNLY;
• or the genes S100A9, IL2RB, KLRK1, HCK, GNLY, CTSZ, ARF5, and UTP14C, or
• (iii) Equivalent Expression Profile of anyone of the expression profiles of (i) and (ii),
• and optionally one or more housekeeping gene(s)
• (c) comparing the obtained expression profile with at least one reference expression profile,
• (d) determining the responding or non-responding phenotype of said RA-suffering subject from said comparison,
• (e) determining a dose of CyTD, and
• (f) administering the said dose of CyTD.

A method of treatment of a subject suffering from an inflammatory disease, comprising the steps of:

• (a) determining from a biological sample of said subject an expression profile comprising or consisting of:
• (i) the gene MAPK14;
• or the genes MAPK14 and S100A9;
• or the genes MAPK14 and GNLY;
• or the 61 genes of Table 2,
• (ii) the gene S100A9;
• or the genes S100A9, IL2RB, and CASP5;
• or the genes S100A9, IL2RB, KLRK1, HCK, and GNLY;
• or the genes S100A9, IL2RB, KLRK1, HCK, GNLY, CTSZ, ARF5, and UTP14C, or
• (iii) Equivalent Expression Profile of anyone of the expression profiles of (i) and (ii),
• and optionally one or more housekeeping gene(s),
• (b) comparing the obtained expression profile with at least one reference expression profile,
• (c) determining the responding or non-responding phenotype of said subject from said comparison,
• (d) determining a dose of CyTD, and
• (e) administering the said dose of CyTD.