PMID- 19623018 OWN - NLM STAT- MEDLINE DCOM- 20090916 LR - 20090722 IS - 1534-6080 (Electronic) IS - 0041-1337 (Linking) VI - 88 IP - 2 DP - 2009 Jul 27 TI - Intact HLA not beta2m-free heavy chain-specific HLA class I antibodies are predictive of graft failure. PG - 226-30 LID - 10.1097/TP.0b013e3181ac6198 [doi] AB - BACKGROUND: We investigated the effects of intact and beta2m-free heavy chain (HC)-specific human leukocyte antigen (HLA) class I antibodies on long-term graft survival. METHODS: HLA class I mixed antigen beads were used to detect intact and beta2m-free HC-specific antibodies, whereas elution buffer-treated beads were used to detect antibodies against beta2m-free HC. Donor-specific antibodies (DSAs) were identified using single-antigen beads. Complement-dependent cytotoxicity assays were performed to determine the cytotoxicity of DSA. RESULTS: Three hundred seventy-nine of 994 of patients (38%) had antibodies against intact HLA and beta2m-free HC. There was no survival rate difference between antibody-positive and -negative groups. When the 379 antibody-positive patients were further tested with beta2m-free HC-coated beads, 179 of them with antibodies only against intact form of antigens had a 4-year graft survival rate of 76%, which is significantly lower than that of 200 patients with antibodies against beta2m-free HC of HLA antigens (88%, P=0.0056). Patients with intact antigen specific DSAs had a significantly lower graft survival rate as compared with those with no DSAs (70% vs. 89%, P=0.0073). More patients with strong donor-specific cytotoxic antibodies lost allografts than those with weak-cytotoxic or noncytotoxic antibodies. However, cytotoxic activity of DSA was not correlated to antibody level. CONCLUSIONS: We concluded that intact antigen-specific antibodies, especially DSAs, are predictive of graft failure. DSAs were not always cytotoxic. Strong cytotoxic activity of DSA was associated with a higher rate of graft loss but not correlated to the antibody level. Antibodies against beta2m-free HC negatively interfere with the predictive value of intact antigen-specific antibodies. FAU - Cai, Junchao AU - Cai J AD - Terasaki Foundation Laboratory, Los Angeles, CA, USA. terasaki@terasakilab.org FAU - Terasaki, Paul I AU - Terasaki PI FAU - Anderson, Naomi AU - Anderson N FAU - Lachmann, Nils AU - Lachmann N FAU - Schonemann, Constanze AU - Schonemann C LA - eng PT - Journal Article PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Autoantibodies) RN - 0 (HLA Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Immunoglobulin Heavy Chains) RN - 0 (Isoantibodies) SB - IM MH - Adult MH - Autoantibodies/immunology MH - Female MH - Graft Rejection/*immunology MH - Graft Survival/*immunology MH - HLA Antigens/immunology MH - Histocompatibility Antigens Class I/*immunology MH - Humans MH - Immunoglobulin Heavy Chains/immunology MH - Isoantibodies/immunology MH - Kidney Transplantation/*immunology MH - Male MH - Middle Aged MH - Predictive Value of Tests MH - Retrospective Studies MH - Transplantation, Homologous/immunology MH - Treatment Failure EDAT- 2009/07/23 09:00 MHDA- 2009/09/17 06:00 CRDT- 2009/07/23 09:00 PHST- 2009/07/23 09:00 [entrez] PHST- 2009/07/23 09:00 [pubmed] PHST- 2009/09/17 06:00 [medline] AID - 00007890-200907270-00012 [pii] AID - 10.1097/TP.0b013e3181ac6198 [doi] PST - ppublish SO - Transplantation. 2009 Jul 27;88(2):226-30. doi: 10.1097/TP.0b013e3181ac6198.