Therapeutic methods and compositions

Abstract

Methods for diagnosing or treating immune disorders in a subject are provided. The methods are based on the detection or modulation of Refractory state Inducing Factor (RIF).

1 . (canceled) 
     
     
         2 . A method for stimulating an immune response in a HIV-infected subject, or for treating AIDS in a HIV-infected subject, comprising administering to the subject an effective amount of an anti-GIBsPLA2 antibody or a fragment thereof that binds to secreted phospholipase A2 group IB (GIBsPLA2), wherein the HIV-infected subject is a CD4 non-responder (CD4-NR). 
     
     
         3 . The method of  claim 2 , wherein the HIV-infected subject has low CD4 counts after prolonged ART. 
     
     
         4 . The method of  claim 2 , wherein said method increases CD4 counts in the HIV-infected subject having low CD4 counts after prolonged ART. 
     
     
         5 . The method of  claim 2 , wherein said method induces or stimulates CD4 T cells activation in the subject. 
     
     
         6 . The method of  claim 2 , wherein said method suppresses or reverses HIV-mediated immunodeficiency. 
     
     
         7 . The method of  claim 2 , wherein the anti-GIBsPLA2 antibody is selected from anti-GIBsPLA2 polyclonal antibodies, anti-GIBsPLA2 monoclonal antibodies or GIBsPLA2-binding fragments thereof selected from F(ab′)2 and Fab fragments, single-chain variable fragments (scFvs), single-domain antibody fragments (VHHs or Nanobodies) or bivalent antibody fragments (diabodies). 
     
     
         8 . The method of  claim 2 , wherein the anti-GIBsPLA2 antibody or a fragment thereof, is human or humanized. 
     
     
         9 . The method of  claim 2 , wherein GIBsPLA2 is a protein comprising amino acid residues 23-148 of SEQ ID NO: 2 or a naturally-occurring variant thereof. 
     
     
         10 . The method of  claim 2 , wherein the anti-GIBsPLA2 antibody or a fragment thereof inhibits the expression or activity of GIBsPLA2. 
     
     
         11 . The method of  claim 10 , wherein the activity of GIBsPLA2 is selected from induction of formation of membrane microdomains (MMD) in CD4 T cells or rendering CD4 T cells refractory to interleukin signaling. 
     
     
         12 . The method of  claim 2 , wherein the anti-GIBsPLA2 antibody is administered intramuscularly, subcutaneously, transdermally, intravenously, intraarterially, nasally, orally, mucosally, rectally or by inhalation.