Ligands, including antibodies, showing reactivity against endocrine cells

Abstract

The invention provides monoclonal and polyclonal antibodies recognising molecules on secretory cells of various tissue targets of autoimmune disease allowing a unifying method of preventing and treating autoimmune diseases and other conditions where hormonal dysregulation, hyperinsulinaemia and insulin resistance are involved. It also provides a method for detecting similar antibodies in human sera or other body fluids which can be used in the development of diagnostic kits. Treatment methods arising from this invention comprise the administration of preparations of the antibodies, their target molecules and vectors containing coding sequences of the antibodies and their target molecules.

1 . A monoclonal or polyclonal antibody or equivalent ligand with reactivity against an anti-TCR Vβ antibody, for use as a pharmaceutical or as a diagnostic agent.  
     
     
         2 . An antibody with reactivity against an anti-TCR Vβ antibody, for use as a pharmaceutical or as a diagnostic agent.  
     
     
         3 . An antibody or equivalent ligand according to  claim 1  with reactivity against both an anti-TCR Vβ antibody and a GPI-linked TCR Vβ chain, for use as a pharmaceutical or as a diagnostic agent.  
     
     
         4 . An antibody or equivalent ligand according to  claim 1  with reactivity against any one of the following compounds: a phospholipid, a phospholipid glycan, single stranded DNA and double stranded DNA, for use as a pharmaceutical or as a diagnostic agent.  
     
     
         5 . An antibody according to  claim 1  which is a monoclonal antibody, for use as a pharmaceutical or as a diagnostic agent.  
     
     
         6 . An antibody or equivalent ligand according to  claim 1  which is of vertebrate or invertebrate origin, for use as a pharmaceutical or as a diagnostic agent.  
     
     
         7 . An antibody or equivalent ligand according to  claim 1  that is derived from B cells immortalised by Epstein-Barr virus transformation or other methods using B cells obtained from healthy or diseased humans or animals.  
     
     
         8 . An antibody or equivalent ligand according to  claim 1  which is isolated by passing body fluid from animals or humans down an antigen conjugated column, for use as a pharmaceutical or as a diagnostic agent.  
     
     
         9 . An antibody or equivalent ligand according to  claim 8  wherein said animals or humans are immunised with antigen, are diseased or have been manipulated by drug or by diet so as to develop a disease, for use as a pharmaceutical or as a diagnostic agent.  
     
     
         10 . An antibody or equivalent ligand according to  claim 1  which is chemically-modified, bound to a biological or synthetic substance, or which is conjugated to an enzyme, an indicator compound, a drug, a toxin or a radioactive label, for use as a pharmaceutical or as a diagnostic agent.  
     
     
         11 . (canceled)  
     
     
         12 . A peptide, oligopeptide, polypeptide or protein that is bound by a monoclonal or polyclonal antibody or equivalent ligand according to  claim 1 , which is not an anti-TCR Vβ antibody, for use as a pharmaceutical or as a diagnostic agent.  
     
     
         13 . (canceled)  
     
     
         14 . A peptide, oligopeptide, polypeptide or protein comprising the sequence of ESRP1.  
     
     
         15 . A peptide, oligopeptide, polypeptide or protein according to  claim 14 , for use as a pharmaceutical or as a diagnostic agent.  
     
     
         16 . (canceled)  
     
     
         17 . A cDNA, RNA or genomic DNA sequence encoding a monoclonal or polyclonal antibody or equivalent ligand with reactivity against an anti-TCR Vβ antibody or encoding a peptide, oligopeptide, polypeptide or protein that is bound by a monoclonal or polyclonal antibody or equivalent ligand with reactivity against an anti-TCR Vβ antibody, which is not an anti-TCR Vβ antibody for use as a pharmaceutical or as a diagnostic agent.  
     
     
         18 . A cDNA, RNA or genomic DNA sequence encoding ESRP1.  
     
     
         19 . A bacteriophage clone comprising a cDNA, RNA or genomic DNA sequence according to  claim 18 .  
     
     
         20 . A biologically functional plasmid or viral vector comprising a cDNA, RNA or genomic DNA sequence according to  claim 19 .  
     
     
         21 . A bacteriophage clone, biologically functional plasmid or viral vector comprising a cDNA, RNA or genomic DNA sequence according to  claim 18 , for use as a pharmaceutical or as a diagnostic agent.  
     
     
         22 . A host cell that is stably transformed or transfected with a plasmid or vector according to  claim 20 .  
     
     
         23 . A method for detection of a naturally-occurring autoantibody, comprising contacting a blood, plasma or serum sample or other body fluid with a monoclonal or polyclonal antibody or equivalent ligand according to  claim 1  and with target molecules and assessing the amount of said naturally-occurring autoantibody that binds specifically to the target molecules.  
     
     
         24 . The method of  claim 23  wherein said antibody, fragment thereof or functional equivalent is labelled so that the labelled antibody or equivalent ligand competes with the autoantibodies for the target molecules to form complexes and whereby the amount of label bound in said complexes is inversely proportional to the concentration of autoantibodies present in said sample.  
     
     
         25 . The method of  claim 24 , wherein said antibody or equivalent ligand is labelled with an enzyme so that the formation of said complexes inhibits or inactivates the activity of said enzyme and whereby the degree of inhibition or activation is inversely proportional to the concentration of autoantibodies that are present in said sample.  
     
     
         26 . A method according to  claim 24 , wherein said target molecules are bound to an enzyme linked to a substrate such that binding of antibody to the target molecules activates the enzyme and causes a colour change that is measurable spectrophotometrically.  
     
     
         27 . A method according to  claim 23 , wherein said target molecules are bound to an enzyme linked to a substrate and are present on a dipstick which can be contacted with said sample.  
     
     
         28 . A method according to  claim 24 , wherein said target molecule is an anti-TCR Vβ polyclonal or monoclonal immunoglobulin molecule or any part thereof that identifies at least one epitope on T cell receptor Vβ chains in humans or any animal species.  
     
     
         29 . A method of treatment of IDDM, NIDDM, or organ or non-organ specific autoimmune disease, cardiovascular disease, cancer cachexia and cancer or any other diseases where anti-phospholipid antibodies and/or hyperinsulinaemia and insulin resistance are present involving appying to a patient a monoclonal or polyclonal antibody or equivalent ligand with reactivity against an anti-TCR Vβ antibody or a peptide, oligopeptide, polypeptide or protein that is bound by a monoclonal or polyclonal antibody or equivalent ligand with reactivity against an anti-TCR Vβ antibody, which is not an anti-TCR Vβ antibody, in an effective amount, optionally in conjunction with a pharmaceutically-acceptable carrier.