Interferon alpha-induced pharmacodynamic markers

Abstract

The present invention encompasses type-I IFN and IFNα-induced PD marker expression profiles, kits, and methods for identifying such IFNα-induced PD marker expression profiles. The type-I IFN and IFNα-induced PD marker expression profiles may also be used in, for example, methods of treating patients having a type-I IFN or IFNα-mediated disorder, methods of monitoring disease progression of patients receiving treatment with a therapeutic agent that binds to and modulates IFNα activity, identifying patients as candidates to receive a therapeutic that binds to and neutralizes IFNα activity, and in diagnosing or providing a prognosis to patients having IFNα-induced disorders.

1 - 225 . (canceled) 
     
     
         226 . A method for treating myositis, comprising:
 administering MEDI-546 to a subject identified as having an increase in the mRNA of at least two genes chosen from
 interferon-induced protein 44 (IFI44), 
 interferon alpha-inducible protein 6 (IFI6), 
 radical S-adenosyl methionine domain containing 2 (RSAD2), 
 sterile alpha motif domain containing 9-like (SAMD9L), 
 interferon-inducible guanylate binding protein 1 (GBP1), 
 2′-5′-oligoadenylate synthetase 2 (OAS1), 
 XIAP associated factor-1 (BIRC4BP), and 
 SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2) 
   in a biological sample, thereby treating the myositis.   
     
     
         227 . The method of  claim 226 , wherein the increase in the mRNA of the at least two genes is an average increase in the mRNA for the at least two genes. 
     
     
         228 . The method of  claim 227 , wherein the average increase is a mean increase or median increase. 
     
     
         229 . The method of  claim 226 , wherein the at least two genes comprise IFI44 and RSAD2. 
     
     
         230 . The method of  claim 226 , wherein an increase in the mRNA of at least three genes chosen from IFI44, IFI6, RSAD2, SAMD9L, GBP1, OAS1, BIRC4BP and SRBAP2, has been detected in the sample. 
     
     
         231 . The method of  claim 230 , wherein the at least three genes comprise IFI44, IFI6 and RSAD2. 
     
     
         232 . The method of  claim 226 , wherein the sample is whole blood or blood serum. 
     
     
         233 . The method of  claim 226 , wherein the subject is in need of treatment of dermatomyositis (DM). 
     
     
         234 . The method of  claim 226 , wherein the subject is in need of treatment of polymyositis (PM). 
     
     
         235 . The method of  claim 226 , wherein the subject is in need of treatment of inclusion body myositis (IBM). 
     
     
         236 . The method of  claim 226 , which comprises detecting the mRNA of the at least two genes in the sample from the subject. 
     
     
         237 . The method of  claim 236 , comprising:
 (i) isolating RNA from the sample;   (ii) synthesizing cDNA from the RNA;   (iii) hybridizing the cDNA with oligonucleotides that hybridize to the polynucleotides, and   (iv) amplifying the cDNA and detecting the amplified products.