Immune complex binding by immunocamouflaged [poly(ethylene glycol)‐grafted] erythrocytes

• Published in: American journal of hematology Vol. 82; no. 11; pp. 970 - 975
• Main Authors: Bradley, Amanda J., Scott, Mark D.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2007; Wiley-Liss
• Subjects: ABO Blood-Group System - immunology; Antigen-Antibody Complex - chemistry; Antigen-Antibody Complex - immunology; Biological and medical sciences; Blood Group Incompatibility - immunology; Blood Group Incompatibility - prevention & control; Erythrocyte Transfusion - methods; Erythrocytes - chemistry; Erythrocytes - immunology; Hematologic and hematopoietic diseases; Humans; In Vitro Techniques; Medical sciences; Polyethylene Glycols - chemistry; Receptors, Complement 3b - chemistry; Receptors, Complement 3b - immunology; Rh-Hr Blood-Group System - immunology; Red blood cell; Graft; Blood cell; Hematology; Ethylene; Immune complex
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.20956

Immune complexes (IC) are constantly formed at low levels in normal individuals. In humans, the red blood cell (RBC) complement receptor 1 (CR1) plays the dominant role in the IC binding and clearance. Over the last several years, we have investigated the potential utility of immunocamouflaged (methoxypoly(ethylene glycol) [mPEG] grafted) RBC to attenuate the risk of alloimmunization. Because the grafted polymer nonspecifically camouflages membrane proteins, its effects on CR1 detection and IC binding were assessed. The dose dependent (0–2.5 mM) effects of activated mPEG (CmPEG, 5 kDa; and BTCmPEG, 5 and 20 kDa) on CR1 detection and the binding of artificially generated IC [C3b coated alkaline phosphatase and antialkaline phosphatase complexes] to control and pegylated RBC was investigated by flow cytometry. In contrast to selected non‐ABO blood group antigens, grafted mPEG did not effectively camouflage CR1. Surprisingly, however, even very low grafting concentrations of mPEG (≥0.3 mM) resulted in a ≥95% loss in IC binding. Further reductions in grafting concentration (0.15 and 0.03 mM mPEG) still yielded decreased IC binding of ∼60 and 40%, respectively. Importantly, unactivated mPEG had minimal effects on IC binding. These data demonstrate that even small amounts of grafted mPEG interfere with the multivalent CR1‐IC interaction necessary for high affinity IC binding, hence large volume transfusions of mPEG‐RBC may be contraindicated in patients with pre‐existing IC disease. Whether this concern is of clinical significance in healthy humans is less clear due to dilutional effects and the presence of secondary clearance pathways. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.