Interactions of IgM ABO antibodies and complement with methoxy-PEG-modified human RBCs

被引:41
作者
Bradley, AJ
Test, ST
Murad, KL
Mitsuyoshi, J
Scott, MD
机构
[1] Albany Med Coll, Ctr Immunol & Microbial Dis, Albany, NY 12208 USA
[2] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA
关键词
D O I
10.1046/j.1537-2995.2001.41101225.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. STUDY DESIGN AND 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-RBCswere 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. CONCLUSION: 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.
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页码:1225 / 1233
页数:9
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