Structural and functional consequences of antigenic modulation of red blood cells with methoxypoly(ethylene glycol)

We previously showed that the covalent modification of the red blood cell ( RBC) surface with methoxypoly(ethylene glycol) [mPEG; MW similar to 5 kD] c ould significantly attenuate the immunologic recognition of surface antigen s. However, to make these antigenically silent RBC a clinically viable opti on, the mPEG-modified RBC must maintain normal cellular structure and funct ions. To this end, mPEG-derivatization was found to have no significant det rimental effects on RBC structure or function at concentrations that effect ively blocked antigenic recognition of a variety of RBC antigens. Important ly, RBC lysis, morphology, and hemoglobin oxidation state were unaffected b y mPEG-modification. Furthermore, as shown by functional studies of Band 3, a major site of modification, PEG-binding does not affect protein function , as evidenced by normal SO4- flux. Similarly, Na+ and K+ homeostasis were unaffected. The functional aspects of the mPEG-modified RBC were also maint ained, as evidenced by normal oxygen binding and cellular deformability. Pe rhaps most importantly, mPEG-derivatized mouse RBC showed normal in vivo su rvival (similar to 50 days) with no sensitization after repeated transfusio ns. These data further support the hypothesis that the covalent attachment of nonimmunogenic materials (eg. mPEG) to intact RBC may have significant a pplication in transfusion medicine, especially for the chronically transfus ed and/or allosensitized patient. (C) 1999 by The American Society of Hemat ology.