Humoral sensitization against rejected grafts: specific antibodies to graft immunogenic amino acid triplets.
Humoral sensitization against immunogenic amino acid (aa) triplets expressed on a rejected graft was analyzed in 83 retransplant candidates. All patients had lost a graft with HLA-A,-B mismatches. The alloantibodies were detected by a complement-dependent cytotoxicity (CDC) technique and an ELISA method in parallel; they were classified as HLA graft-specific (GS) and non-GS antibodies. The aa triplet specificity of the antibodies was assessed using the HLAMatchmaker algorithm. HLA class I antibodies were detected in 74 of 78 (94%) cases, including GS reactivity in 55 (74.3%) and non-GS in 72 (97.2%), either alone (n = 19) or in parallel with GS antibodies (n = 53). For all HLA-GS-antibody-reactive patients, we defined the specificity against immunogenic aa triplets on the previous graft. Moreover, antibodies specific to graft aa triplets were observed within the non-GS antibodies among 19 of 19 and 28 of 53 cases, respectively. Therefore, aa triplet-specific antibodies against the rejected graft were present in all 74 cases with HLA class I antibodies. Antibodies against aa triplets expressed on all HLA class I-mismatched graft antigens were present in 73% of cases. The high extent of humoral alloreactivity against a rejected graft supports the decision to avoid repeated exposure to immunogenic aa triplet mismatches on a second graft. An accurate analysis for performed antibodies in these cases may be beneficial to select the most suitable second donor.
Iniotaki-Theodoraki
A
A
National Tissue Typing Center, General Hospital of Athens, Athens, Greece. gtheo@bigfoot.com
Kalogeropoulou
E
E
Apostolaki
M
M
Doxiadis
I N
IN
Stavropoulos-Giokas
C
C
D000917:Antibody Formation / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology*; D012086:Reoperation
D006680:HLA Antigens; D007518:Isoantibodies; D009842:Oligopeptides