IMMUNE COMPLEX BINDING BY MODIFIED C-REACTIVE PROTEIN

IMMUNE COMPLEXES (ICS) ARE FORMED BY THE BINDING OF ANTIBODIES WITH ANTIGENS, THE ANTIGENS BEING COMPONENTS OF INFECTIOUS ORGANISMS, OTHER MOLECULES FOREIGN TO THE HOST ORGANISM, TUMOR-ASSOCIATED MOLECULES, AND IN MANY DISEASES, NORMAL TISSUE MOLECULAR COMPONENTS. ICS ARE REMOVED FROM THE CIRCULATION AND TISSUES BY A VARIETY OF NORMAL MECHANISMS. HOWEVER, THEIR CONTINUED PRESENCE IN AUTOIMMUNE, MALIGNANT AND INFECTIOUS DISEASES, AND DEPOSITION IN TISSUES, CONTRIBUTES TO COMPROMISED IMMUNE SYSTEM FUNCTION AND INFLAMMATORY PATHOLOGY. IT IS THE LONG-TERM OBJECTIVE OF THIS APPLICATION TO DEVISE A TECHNOLOGY FOR THE EXTRACORPOREAL REMOVAL OF ICS FROM BLOOD AS AN EFFICACIOUS TREATMENT MODALITY FOR IC-INVOLVED DISEASES. WE HAVE DISCOVERED THAT A MODIFIED FORM OF A NORMAL HUMAN PROTEIN, ELICITED IN RESPONSE TO INFLAMMATORY STIMULI, HAS THE ABILITY TO SELECTIVELY BIND ICS. THIS IS ARECENT AND HERETOFORE UNKNOWN FUNCTION OF THIS MOLECULE. THE SPECIFICITY AND EFFICIENCY OF THE MOLECULE'S BINDING TO ICS WILL BE ESTABLISHED BY THE RESEARCH PROPOSED IN THIS APPLICATION BY USING: MODEL IN VITRO-FORMED ICS, ICS DEVELOPED BY ANTIGEN-INDUCED IC DISEASE IN EXPERIMENTAL ANIMALS, AND WITH ICS IN HUMAN SERA DERIVED FROM INDIVIDUALSWITH DIFFERENT IC-INVOLVED DISEASES. THE TECHNOLOGY WILL THEN BE EXTENDED TO THE DEVELOPMENT OF AN EXTRACORPOREAL DEVICE FOR CLINICAL TRIALS. THE POSSIBLE USE OF THE IC-BINDING PROTEIN FOR THE QUANTITATION OF ICS WILL ALSO BE EXPLORED.