G6(W)
DE NOVO HLA-DQ DONOR SPECIFIC ANTIBODIES ARE ASSOCIATED WITH A HIGH
RISK OF REJECTION AND TRANSPLANT GLOMERULOPATHY
Willicombe, M, Brookes, P, Roufosse, C, Galliford, J, McLean, A, Cook, T, Cairns, T, Taube, D
Imperial College Kidney and Transplant Centre, Hammersmith, London
BACKGROUND: It has long been established that a mismatch at the HLA-DR loci in renal
transplantation is associated with inferior allograft survival and this has been incorporated within the
NHS Blood and Transplant organ allocation scheme in the UK. More recently studies have shown
that HLA Class II donor specific antibodies [DSA] and particularly antibodies against HLA-DQ
specificities are associated with transplant glomerulopathy. The aim of our study is to determine the
incidence and outcomes of patients who develop HLA-DQ DSA post transplant.
METHODS: We retrospectively studied 434 patients who were transplanted at our centre between
2005-2009. [M:F 294:140, mean age at transplant 47.43 ±13.15 yrs, DD:LD 238:196, 1st:2nd grafts
398:36, mean HLA MM 3.26±1.65]. All patients received Alemtuzumab induction and tacrolimus
monotherapy. We excluded ABO and HLA incompatible patients. All donors and recipients were
typed for HLA -A,-B,-Cw,-DR (both DRB1 gene products and those of the other functional DRB
genes) and -DQ antigens. Post transplant patients were screened for DSA at regular intervals or when
clinically indicated using luminex beads. Mean follow up was 23.71±13.96 months.
RESULTS: 155/434 [35.71%] of patients were DQ matched, 39/279 [13.99%] of mismatched DQ
patients developed de novo HLA-DQ DSAbs [DQ+] post transplantation. Patient survival was similar
in the DQ+ and DQ- groups [97.2% in the DQ- group, 100% in the DQ+ group, p=0.29]. Allograft
survival was 87.2% in the DQ+ group and 94.9% in the DQ- group [p=0.053]. DQ+ patients had an
increased risk of experiencing an acute rejection episode. Rejection free survival was 51.3% and
86.3% in the DQ+ and DQ- groups respectively [p<0.001]. DQ+ was associated with ACR and AMR.
ACR free survival was 71.8% in DQ+ patients and 89.6% in DQ- patients [p<0.001]. AMR free
survival was 64.1% and 95.7% in the DQ+ and DQ- groups respectively [p<0.0001]. DQ+ patients
were also at higher risk of developing transplant glomerulopathy, with a TG free survival of 79.5% in
the DQ+ group compared with 98.7% in the DQ- group [p<0.0001].
CONCLUSION: This study shows that the de novo DQ DSAbs are associated with acute rejection
and transplant glomerulopathy with a trend to inferior short term allograft survival.