Phosphorycholine conjugates and corresponding antibodies

Abstract

In subjects with hypertension, increases in intima-media thickness (IMT) at four years were less in subjects also having high autoantibodies particularly IgM, to phosphorylcholine. The presence or absence of autoantibodies, particularly IgM, against phosphrylcholine is thus related to an increased or decreased risk of developing ischemic cardiovascular diseases. A method to determining antibodies, particularly IgM antibodies, toward phosphorylcholine is proposed in this invention to identify subjects at risk of developing ischemic cardiovascular diseases. Animal experiments show that medium to high levels of antibodies, particularly IgM antibodies, can be detected in plasma after active immunization with a keyhole limpet hemocyanin (KLH)-phosphorylcholine conjugate. Pharmaceutical compositions comprising a phosphorylcholine conjugate or antibody preparations, for example a monoclonal antibody, with specificity to a phosphorylcholine conjugate is proposed as is use of these compositions as active or passive immunogens in the treatment or prevention of atherosclerosis.

1 . Use of a pharmaceutical composition comprising an antibody preparation, for example a monoclonal antibody, with specificity to a phosphorylcholine conjugate, in the manufacture of a medicament for immunization and treatment of humans against atherosclerosis or an atherosclerotic related disease. 
     
     
         2 - 8 . (canceled) 
     
     
         9 . A method for assessing a human patient's risk of developing or progression of cardiovascular disease comprising assessing said patient's levels of antibodies reactive with the phosphorylcholine conjugate, wherein low levels of antibody reactive with the phosphorylcholine conjugate are predictive of the occurrence of cardiovascular disease in a healthy human patient. 
     
     
         10 . The method of  claim 9 . wherein the cardiovascular disease is ischemic cardiovascular disease. 
     
     
         11 . The method of  claim 9 , wherein the cardiovascular disease is atherosclerosis. 
     
     
         12 . The method of  claim 9 , wherein the patient's levels of IgM antibodies reactive with the phosphorylcholine conjugate are assessed. 
     
     
         13 . The method of  claim 9 , wherein the patient's levels of IgG antibodies reactive with the phosphorylcholine conjugate are assessed. 
     
     
         14 . The method of  claim 9 , wherein phosphorylcholine is linked to a carrier via a spacer. 
     
     
         15 . The method of  claim 9 , wherein the phosphorylcholine conjugate comprises-phosphorylcholine linked to a protein carrier, optionally via a spacer. 
     
     
         16 . The method of  claim 15 , wherein the protein is KLH (keyhole limpet hemocyanin) or human serum albumin (HSA). 
     
     
         17 . The method of  claim 9 , wherein the phosphorylcholine conjugate comprises-phosphorylcholine linked to a latex bead, optionally via a spacer. 
     
     
         18 . The method of  claim 9 , wherein the assay is an immunoassay.