The development of donor-specific HLA antibodies (DSA) represents the major risk factor of graft failure in kidney transplantation. However, some patients show persistent presence of circulating DSA without occurrence of graft loss. Solid phase assays, such as Luminex Single Antigen (LSA) beads, are highly sensitive in detecting DSA but not very predictive of transplant outcome because of detection of complement-fixing and less clinically relevant no complement-fixing antibodies. Using the novel LSA-C1q assay, we investigate the clinical relevance of de novo DSA in relation to their capability to fix complement. In serum samples from 53 kidney transplanted patients who had developed IgG-LSA DSA after transplantation, we measured complementfixing ability of detected DSA by Class I and Class II LSA-C1q assay. As for transplant outcome, 32 (60%) patients suffered graft failure and 21 (40%) had good graft function during the follow up period. As for complement-fixing capability of DSA, 35 patients showed production of C1q-positive DSA; the remaining 18 produced C1q-negative DSA. C1q-positive DSA were present in all but three patient who had graft failure; only six of the 21 patients showing C1q-negative DSA suffered graft failure (91% vs. 29% respectively, P?¬0.0001). As for HLA specificity of DSA, C1q-positive DQA antibodies were only present in three patients showing good graft function. On the contrary, DQB-DSA were present in 21 patients showing C1q-positive HLA antibodies; all but one of these patients suffered graft loss. In conclusion our data suggest that C1q-LSA assay shows the capability to identify the subset of IgG-LSA DSA strongly associated to graft loss in kidney transplantation. Moreover the ability of C1q assay in distinguishing less harmful no complement-fixing DSA from clinically relevant C1q-fixing DSA represent a non-invasive tool for identifying patients who need specific immunosuppressive-therapy strategy to prolong graft survival.
DE NOVO PRODUCTION OF C1Q-FIXING DONOR-SPECIFIC ANTIBODIES IS ASSOCIATED WITH KIDNEY ALLOGRAFT LOSS
Piazza Antonina;Poggi Elvira;Ozzella Giuseppina;
2013
Abstract
The development of donor-specific HLA antibodies (DSA) represents the major risk factor of graft failure in kidney transplantation. However, some patients show persistent presence of circulating DSA without occurrence of graft loss. Solid phase assays, such as Luminex Single Antigen (LSA) beads, are highly sensitive in detecting DSA but not very predictive of transplant outcome because of detection of complement-fixing and less clinically relevant no complement-fixing antibodies. Using the novel LSA-C1q assay, we investigate the clinical relevance of de novo DSA in relation to their capability to fix complement. In serum samples from 53 kidney transplanted patients who had developed IgG-LSA DSA after transplantation, we measured complementfixing ability of detected DSA by Class I and Class II LSA-C1q assay. As for transplant outcome, 32 (60%) patients suffered graft failure and 21 (40%) had good graft function during the follow up period. As for complement-fixing capability of DSA, 35 patients showed production of C1q-positive DSA; the remaining 18 produced C1q-negative DSA. C1q-positive DSA were present in all but three patient who had graft failure; only six of the 21 patients showing C1q-negative DSA suffered graft failure (91% vs. 29% respectively, P?¬0.0001). As for HLA specificity of DSA, C1q-positive DQA antibodies were only present in three patients showing good graft function. On the contrary, DQB-DSA were present in 21 patients showing C1q-positive HLA antibodies; all but one of these patients suffered graft loss. In conclusion our data suggest that C1q-LSA assay shows the capability to identify the subset of IgG-LSA DSA strongly associated to graft loss in kidney transplantation. Moreover the ability of C1q assay in distinguishing less harmful no complement-fixing DSA from clinically relevant C1q-fixing DSA represent a non-invasive tool for identifying patients who need specific immunosuppressive-therapy strategy to prolong graft survival.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
