title: Intravascular survival of red cells coated with a mutated human anti-D antibody engineered to lack destructive activity.
abstract: Alloimmune feto-maternal destruction of blood cells is thought to be mediated by binding of alloantibodies to Fc receptors on effector cells. Blocking the antigen using inert antibodies might prolong cell survival. We have performed a "proof of principle" study in volunteers to measure the intravascular survival of autologous red cells coated with human recombinant IgG antibody containing a novel constant region, G1Deltanab, devoid of in vitro cytotoxic activity. RhD-positive red blood cells (RBCs), labeled with chromium-51 or technetium-99m, were separately coated to equal levels with wild-type IgG1 or G1Deltanab anti-D antibody (Fog-1). After re-injection, there was complete, irreversible clearance of IgG1-coated RBCs by 200 minutes, concomitant with appearance of radiolabel in plasma. Gamma camera imaging revealed accumulation in spleen and, at higher coating levels, in liver. In contrast, clearance of G1Deltanab-coated cells was slower, incomplete, and transient, with whole blood counts falling to 7% to 38% injected dose by about 200 minutes before increasing to 12% to 67% thereafter. There was no appearance of plasma radiolabel and no hepatic accumulation. These findings suggest that G1Deltanab-coated RBCs were not hemolysed but temporarily sequestered in the spleen and that our approach merits investigation in larger studies.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 2PT, United Kingdom.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Armour
authors.forename: David R
authors.initials: DR
authors.lastname: Parry-Jones
authors.forename: Nigel
authors.initials: N
authors.lastname: Beharry
authors.forename: James R
authors.initials: JR
authors.lastname: Ballinger
authors.forename: Rosey
authors.initials: R
authors.lastname: Mushens
authors.forename: R Keith
authors.initials: RK
authors.lastname: Williams
authors.forename: Cynthia
authors.initials: C
authors.lastname: Beatty
authors.forename: Simon
authors.initials: S
authors.lastname: Stanworth
authors.forename: Paul
authors.initials: P
authors.lastname: Lloyd-Evans
authors.forename: Marion
authors.initials: M
authors.lastname: Scott
authors.forename: Michael R
authors.initials: MR
authors.lastname: Clark
authors.forename: A Michael
authors.initials: AM
authors.lastname: Peters
authors.forename: Lorna M
authors.initials: LM
authors.lastname: Williamson
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D001772:Blood Cell Count; D002470:Cell Survival; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000166:cytology* / Q000276:immunology*; D005818:Genetic Engineering; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007518:Isoantibodies / Q000235:genetics* / Q000276:immunology; D018029:Rho(D) Immune Globulin
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007518:Isoantibodies; C061961:RHO(D) antibody; D018029:Rho(D) Immune Globulin