C1Q-FIXING HLA ANTIBODIES AND KIDNEY TRANSPLANTATION

Aim: De novo production 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 dysfunction/loss. Newer solid phase assay Luminex Single Antigen (LSA) beads, is highly sensitive respect to complement-dependent citotoxicity assay but less predictive of transplant outcome because of detection of both complement-fixing and less clinically relevant no complement-fixing HLA antibodies. Methods: Using Class I and II C1q-LSA assay (One Lambda,CA), that identifies antibodies able to fix C1q, we investigate the clinical relevance of de novo HLA-DSA in 40 kidney transplanted patients. As for transplant outcome, 22 patients suffered graft failure (within 10 ± 1 months from DSA appearance) and 18 had good graft function during all the follow up (mean 54 ± 34 months from DSA appearance). Results: Twenty-three patients showed production of C1q-positive DSA while 17 produced C1q-negative DSA. Correlating graft outcome and capability of DSA to fix C1q, graft failure occurred in 20/23 C1q-positive DSA patients; only 2/17 C1q-negative DSA patients suffered graft failure (87% vs.12%, P < 0.0001; RR = 7.39; Sensitivity = 0.91; Specificity = 0.83; PPV = 0.87; NPV = 0.88). It is to underlay that both C1q-positive and C1q-negative DSA were mainly specific for DQ donor mismatched molecules (74% vs. 53%); the 53% of anti-DQ C1q-positive DSA were specific for DQ1 molecules while the 75% of anti-DQ C1q-negative DSA were specific for DQ2 molecules. Conclusions: C1q-LSA assay showed the capability to identify the subset of IgG-LSA DSA strongly associated to antibody-mediated rejection and graft loss in kidney transplantation; moreover, its ability in distinguishing less harmful no complement-fixing DSA from clinically relevant C1q-fixing DSA, allows to identify patients that need specific immunosuppressive strategy to prolong graft survival.