Use of soluble cd164 in inflammatory and/or autoimmune disorders

Abstract

The present invention relates to novel therapeutic uses of soluble proteins comprising the extracellular region of humans CD164, in particular for treating inflammatory and/or autoimmune disorders.

1 - 23 . (canceled)  
     
     
         24 . A method of treating inflammatory and/or autoimmune diseases comprising the administration of a composition comprising a soluble protein comprising a sequence having at least 85% of homology with the mature form of the extracellular domain of human CD 164 (SEQ ID NO: 1).  
     
     
         25 . The method according to  claim 24 , wherein said soluble protein is chosen from: 
 a) SEQ ID NO: 1; or    b) SEQ ID NO: 1 fused to the signal sequence of human CD164.    
     
     
         26 . The method according to  claim 24 , wherein said soluble protein is an active mutein or an isoform of SEQ ID NO: 1.  
     
     
         27 . The method according to  claim 26 , wherein said soluble protein is chosen from: 
 a) MGC-24 (SEQ ID NO: 6); or    b) the mature form of the extracellular domain of any of the following human CD 164 isoforms: CD164-delta 4 (SEQ ID NO: 4), CD164-delta 5 (SEQ ID NO: 5).    
     
     
         28 . The method according to  claim 24 , wherein said soluble protein is glycosylated.  
     
     
         29 . The method according to  claim 28 , wherein said soluble protein is glycosylated at any of the positions as set forth in SEQ ID NO: 1.  
     
     
         30 . The method according to  claim 24 , wherein said soluble protein is phosphorylated.  
     
     
         31 . The method according to  claim 30 , wherein said soluble protein is phosphorylated at any of the positions as set forth in SEQ ID NO: 1.  
     
     
         32 . The method according to  claim 24 , wherein said soluble protein is myristoylated.  
     
     
         33 . The method according to  claim 32 , wherein said soluble protein is myristoylated at any of the positions as set forth in SEQ ID NO: 1.  
     
     
         34 . The method according to  claim 24 , wherein said soluble protein is a soluble fusion protein.  
     
     
         35 . The method according to  claim 34 , wherein said soluble fusion protein comprises a signal sequence.  
     
     
         36 . The method according to  claim 34 , wherein said soluble fusion protein contains a Histidine tag.  
     
     
         37 . The method according to  claim 36 , wherein said soluble fusion protein is SEQ ID NO: 2.  
     
     
         38 . The method according to  claim 34 , wherein said soluble fusion protein comprises an Fc region of an immunoglobulin.  
     
     
         39 . The method according to  claim 24 , wherein said soluble protein is an active derivative, a proteolysis-resistant modified form, a conjugate, a complex, a fraction, a precursor, and/or a salt.  
     
     
         40 . The method according to  claim 24 , wherein said inflammatory and/or autoimmune disease is selected from the group consisting of: multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, osteoarthritis, spondylarthropathies, inflammatory bowel disease, endotoxemia, Crohn's disease, Still's disease, uveitis, Wegener's granulomatosis, Behcet's disease, scleroderma, Sjogren's syndrome, sarcoidosis, pyodema gangrenosum, polymyositis, dermatomyositis, myocarditis, psoriasis, systemic sclerosis, hepatitis C, allergies, allergic inflammation, allergic airway inflammation, chronic obstructive pulmonary disease (COPD), mesenteric infarction, stroke, ulcerative colitis, allergic asthma, bronchial asthma, mesenteric infarction, stroke, fibrosis, post-ischemic inflammation in muscle, kidney and heart, skin inflammation, glomerulonephritis, juvenile onset type I diabetes mellitus, hypersensitivity diseases, viral or acute liver diseases, alcoholic liver failures, tuberculosis, septic shock, HIV-infection, graft-versus-host disease (GVHD) and atherosclerosis.  
     
     
         41 . A method of inhibiting the expression of one or more cytokines in an individual comprising administering to said individual a composition comprising a soluble protein comprising a sequence having at least 85% of homology with the mature form of the extracellular domain of human CD164 (SEQ ID NO: 1).  
     
     
         42 . The method according to  claim 41 , wherein said cytokine is TNF-α, IFN-γ, IL-2, IL-4, IL-5, or IL-10.  
     
     
         43 . A method for identifying compounds as inhibitors of cytokine secretion and expression comprising: 
 a) contacting cells with a composition comprising said compound;    b) contacting cells with a composition comprising a soluble protein comprising a sequence having at least 85% of homology with the mature form of the extracellular domain of human CD164 (SEQ ID NO: 1); and    c) comparing the level of cytokine secretion and expression that is inhibited by the composition comprising said compound with the level of cytokine secretion and expression that is inhibited by the composition comprising said soluble protein.