Adsorption of cytotoxic anti-HLA antibodies with HLA class I immunosorbant beads.
In an effort to generate HLA immunosorbants to specifically remove anti-HLA antibodies from sera of highly sensitized patients, we purified HLA proteins, covalently coupled them onto Sepharose, and adsorbed antisera from five patients with narrowly reactive cytotoxic anti-HLA antibodies and from one patient with broadly reactive antibodies. We found that an HLA-A2 immunosorbant depleted anti-HLA-A2 cytotoxic antibodies, but did not deplete anti-HLA-B7 or anti-HLA-B44 cytotoxic antibodies from the narrowly reactive patient sera. Patient S.C. developed high PRA (81%) with strong cytotoxicity against HLA-A1 and -A2 following rejection of an HLA-A1, -B57 mismatched kidney. We adsorbed his sera with five HLA immunosorbants including HLA-A2 and HLA-A1,28. We found that the HLA-A2 immunosorbant depleted antibodies to HLA-A2+ and HLA-B57+ cells but not to HLA-A1+ cells, while the HLA-A1,A28 immunosorbant depleted antibodies to both HLA-A1+ cells and to the HLA-A28 cross-reactive HLA-A2+ cells. Adsorption was specific for HLA-A alleles to which the patient was sensitized, since neither HLA-B-C immunosorbants (containing HLA-B7, -B8, -B13, -B27, or -B37 plus HLA-C gene products) nor the control immunosorbants (bovine serum albumin or diphtheria toxoid) depleted serum S.C. of cytotoxic anti-HLA antibodies. Our results indicate that HLA immunosorbants are stable to sequential cycles of adsorption and elution, and thus may be of future therapeutic value in treatment of sensitized patients.
Department of Surgery, University of Wisconsin Hospital and Clinics, Madison 53792.
L D
LD
DeVito
H W
HW
Sollinger
W J
WJ
Burlingham
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007163:Immunosorbent Techniques; D007518:Isoantibodies / Q000302:isolation & purification*; D008970:Molecular Weight; D012083:Renin / Q000097:blood
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies; D012083:Renin