Interactions of IgM ABO antibodies and complement with methoxy-PEG-modified human RBCs.
BACKGROUND
RBCs modified with cyanuric chloride activated methoxy-PEG (CmPEG; 5000 Da) are less immunogenic than untreated RBCs, and their use thus may reduce the risk of alloimmunization in chronically transfused patients.


METHODS
To further examine the potential utility of CmPEG-RBCs, the effects of derivatization on an arm of the immune system that plays an important role in transfusion rejection-the complement system--were determined.


RESULTS
When CmPEG-RBCs were incubated in autologous or heterologous ABO-matched serum, no classical or alternative pathway consumption was found, no C3a was generated, no cell-bound C3b or C9 was detected, and no cell lysis occurred. Cell-bound complement regulation was normal for CmPEG-RBCs, as determined by acidified serum or reactive lysis assays. CmPEG-RBCs differed from control RBCs only when incubated in ABO-mismatched serum. In that case, CmPEG modification failed to protect against ABO antibody-dependent complement-mediated lysis. Indeed, cell lysis was actually enhanced at CmPEG concentrations >1.0 mM.


CONCLUSIONS
The enhanced lysis of CmPEG-RBCs in ABO-mismatched serum correlated with increased IgM binding and C3a generation and elevated C3b and C9 membrane deposition. While PEG modification effectively blocks non-ABO antigens, these data show that ABO matching is still required. Once ABO-matched, these modified RBCs retain great potential for the prevention of alloimmunization.
Bradley
A J
AJ
lbany Medical College, Albany, New York 12208, USA.
Test
S T
ST
Murad
K L
KL
Mitsuyoshi
J
J
Scott
M D
MD
D000017:ABO Blood-Group System / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects; D001803:Blood Transfusion / Q000379:methods; D003167:Complement Activation / Q000187:drug effects; D003165:Complement System Proteins / Q000032:analysis / Q000187:drug effects* / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D007518:Isoantibodies / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D065227:Transfusion Reaction
D000017:ABO Blood-Group System; D007075:Immunoglobulin M; D007518:Isoantibodies; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D003165:Complement System Proteins