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-A 1,28. 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 crossreactive 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. © 1990 by Williams & Wilkins.