Bovine hemoglobin (glutamer-250, Hemopure)-specific immunoglobulin G antibody cross-reacts with human hemoglobin but does not lyse red blood cells in vitro

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Abstract

BACKGROUND: Bovine hemoglobin (Hb)-based oxygen carrier (HbOC-201; Hb glutamer-250, Hemopure, Biopure Corp.) is a blood replacement and augmentation drug that increases oxygen-carrying capacity of circulating blood in patients with anemia and acute blood loss. The objective of this study was to assess the biologic significance (cross-reactivity, hemolysis) of humoral immune responses in humans receiving repetitive HbOC-201 administrations. STUDY DESIGN AND METHODS: Serum samples containing immunoglobulin G (IgG) anti-HbOC-201 (n = 146) or no antibody (n = 16) were collected from subjects receiving HbOC-201 in clinical studies. IgG anti-HbOC-201 levels were quantified and the extent of cross-reactivity to human hemoglobin (HuHb) was assessed in direct-binding and competitive-inhibition immunoassays. Serum samples containing the highest levels of IgG anti-HbOC-201 were studied in a complement-mediated hemolysis assay for their ability to lyse human red cells (RBCs). RESULTS: The IgG anti-HbOC-201 levels in the antibody-positive serum samples ranged from 0.7 to 86.8 μg per mL. Of the 146 IgG anti-HbOC-201-positive serum samples, 88.4 percent contained IgG antibodies whose binding to solid-phase HbOC-201 was competitively inhibited by incubation with soluble HuHb (11.6% [<20% inhibition]; 63% [20%-80% inhibition]; and 25.4% [>81% inhibition]). Direct-binding analysis to solid-phase HuHb confirmed that 74 percent contained IgG antibodies reactive with HuHb. Dichotomous competitive inhibition and direct-binding IgG anti-HuHb data correlated significantly (r2 = 0.77, p < 0.001). Serum samples with the highest levels of IgG anti-HuHb, as identified from clinical studies, did not lyse human RBCs in the presence of exogenous complement or induce the direct sensitization of RBCs with human IgG or complement. CONCLUSION: These analyses indicate that HbOC-201 administration elicits IgG antibodies in humans that react with bovine and HuHb, but do not cause hemolysis in vitro.

Original languageEnglish (US)
Pages (from-to)723-728
Number of pages6
JournalTransfusion
Volume47
Issue number4
DOIs
StatePublished - Apr 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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