title: Depletion of anti-Gal(alpha)1-3Gal antibody in baboons by specific alpha-Gal immunoaffinity columns.
abstract: Ongoing studies at our center on facilitating transplantation of discordant xenogeneic organs are focused on tolerance induction. To abrogate hyperacute rejection, we have used adsorption methods to eliminate natural anti-Gal(alpha)1-3Gal (alphaGal) antibodies from the circulation of baboons. We have analyzed data concerning antibody removal in baboons that were 1) immunologically naive, 2) receiving conventional pharmacologic immunosuppressive therapy (IS), and 3) treated with a conditioning regimen for tolerance induction. We compared the efficiency of removing alphaGal antibody 1) by perfusion of whole blood through an alphaGal affinity column (CP; n=5) with 2) perfusion of plasma (separated from cellular components by apheresis) through an alphaGal column (CPA; n=39). Our studies demonstrate that 1) CP and CPA are equally effective in removing anti-alphaGal antibody, 2) CPA is the method of choice if multiple adsorptions are required, 3) CPA in naive animals transiently affects levels of total IgG and IgM, 4) four CPAs repeated at 2-4 day intervals in association with heavy IS reduce the pool of anti-alphaGal antibody and total Ig, and 5) splenectomy and/or IS delay the return of anti-alphaGal antibody.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kozlowski
authors.forename: F L
authors.initials: FL
authors.lastname: Ierino
authors.forename: D
authors.initials: D
authors.lastname: Lambrigts
authors.forename: A
authors.initials: A
authors.lastname: Foley
authors.forename: D
authors.initials: D
authors.lastname: Andrews
authors.forename: M
authors.initials: M
authors.lastname: Awwad
authors.forename: R
authors.initials: R
authors.lastname: Monroy
authors.forename: A B
authors.initials: AB
authors.lastname: Cosimi
authors.forename: D K
authors.initials: DK
authors.lastname: Cooper
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood / Q000302:isolation & purification*; D001779:Blood Coagulation Factors / Q000378:metabolism; D001781:Blood Component Removal; D002846:Chromatography, Affinity / Q000379:methods*; D004187:Disaccharides / Q000276:immunology*; D000939:Epitopes; D006084:Graft Rejection / Q000517:prevention & control; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000097:blood / Q000302:isolation & purification; D007075:Immunoglobulin M / Q000097:blood / Q000302:isolation & purification; D007163:Immunosorbent Techniques; D007166:Immunosuppressive Agents / Q000494:pharmacology; D010215:Papio / Q000276:immunology*; D010477:Perfusion; D013156:Splenectomy; D013552:Swine / Q000276:immunology; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000276:immunology
chemical_list: D000910:Antibodies, Heterophile; D001779:Blood Coagulation Factors; D004187:Disaccharides; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; C055075:galactosyl-(1-3)galactose