OR51 To treat or not to treat: Long term stable kidney allograft function in presence of strong complement-fixing donor-specific antibody (DSA) to HLA-DQ alpha chain

The clinical significance of HLA antibody specific to the DQ alpha chain is controversial. Here we present a case of long term stable kidney allograft function in presence of strong de novo complement-fixing DQA DSA. A 27-year-old Caucasian male (non-sensitized; 0% CPRA) with ESRD to IgA nephropathy received a living donor kidney transplant (TX) 10+ years ago with a negative pre-TX CDC crossmatch (XM). Mismatched donor HLA were A1, A11, B8, DR13, DR17, DR52, DQ2, DQ6. Beginning 6 years post-TX, routine antibody screening by single antigen beads (SAB) revealed the emergence of de novo DQ antibody, with the reactivity to donor DQ2 and DQ6 initially detected at 700–10400 and 100–2400 MFI, respectively. Subsequent SAB profiles indicated that the DSA had progressively converted to be primarily directed against DQA1∗04/05/06, likely a result of sensitization from donor DQA1∗05:01. Epitope analysis suggested that the DSA was directed against a well-defined eplet 40GR3 shared by all DQA1∗04/05/06 alleles and may represent three distinct eplets 40G, 47C, 50V51L53Q, all located in the alpha-1 domain accessible to antibody binding. Testing by phenotype beads confirmed this strong DQA reactivity (5900–14100 MFI) and flow XM with surrogate donors expressing DQA1∗05 were strongly B-cell positive (210–420 MCS), suggesting the DSA was directed against native DQA chain. Functionally, C1q testing demonstrated the DQA DSA’s considerable ability to fix complement (5300–9500 MFI), while CDC XM with DQA1∗05 + surrogate donors were all negative. Despite the prolonged presence of this DQA DSA, other than an episode of acute cellular rejection (Banff II C4d-) diagnosed shortly after transplant which was promptly resolved, the patient’s 10 + years of post-TX course has been unremarkable with a stable kidney function (creatinine 1.5  ±  0.2 mg/dL; BUN 13.4  ±  2.7 mg/dL; GFR 55.0  ±  6.8 mL/min). This case highlights the fact that not all HLA DSA are created equal in terms of their clinical significance, and may also suggest a protective effect of a subset of DSA when directed against only to the DQ alpha chain. Download high-res image (313KB) Download full-size image