STUDY OF AN ANTI-HUMAN TRANSTHYRETIN IMMUNOADSORBENT - INFLUENCE OF COUPLING CHEMISTRY ON BINDING-CAPACITY AND LIGAND LEAKAGE

A variant of transthyretin (TTR Val30Met) has been identified as the m ain protein precursor of the amyloid fibrils deposited in familial amy loidotic polyneuropathy (FAP). Specific removal of TTR in an extracorp oreal immunoadsorption procedure is currently under investigation as a possible treatment of FAP. Immunoadsorbents were constructed by immob ilizing murine anti-TTR monoclonal antibody 88.6.BA9 onto agarose gel supports via several different coupling chemistries. The influence of coupling conditions such as pH and antibody density, and of perfusion variables,such as antigen concentration and applied flow-rate, on the TTR capture efficiency, was determined. Cyanogen bromide-, carbonyldii midazole- and aldehyde-activated (ALD) supports conjugated with antibo dy at optimal pH, provided immunoadsorbents with comparable TTR bindin g capacities. Regarding stability, leakage was lowest for the ALD base d immunoadsorbents, particularly at high pH. (C) 1998 Elsevier Science B.V.