De novo DQ donor-specific antibodies are associated with a significant risk of antibody-mediated rejection and transplant glomerulopathy.
BACKGROUND
The importance of human leukocyte antigen (HLA) matching in renal transplantation is well recognized, with HLA-DR compatibility having the greatest influence. De novo DQ donor-specific antibodies (DSAbs) are the predominant HLA class II DSAb after transplantation. The aim of this study was to establish the incidence and outcomes after the development of DQ DSAbs along with the impact of class II HLA mismatch on their development.


METHODS
We retrospectively analyzed 505 patients who received a renal-alone transplant between 2005 and 2010. We excluded patients who received an ABO- and HLA-incompatible allograft, which we defined as those with a positive crossmatch or preformed DSAbs detected by single-antigen beads only.


RESULTS
Of 505 patients, 92 (18.2%) developed DSAbs, with 50 (54.3%) of these 92 patients having DQ DSAbs. Patients who developed DQ DSAbs were at significant risk for antibody-mediated rejection, transplant glomerulopathy, and allograft loss (P<0.0001). Of 505 patients, 108 (21.4%) were matched at both the DR and DQ loci, 284 (56.2%) were mismatched at both loci, 38 (7.5%) were matched at DR alone, and 75 (14.9%) were matched at DQ alone. Patients mismatched at both DR and DQ were at risk for developing class II DSAbs when compared with those mismatched at either DR or DQ alone, P=0.001, and were at risk for antibody-mediated rejection, P=0.001.


CONCLUSIONS
DQ DSAbs are associated with inferior allograft outcomes. This study shows the importance of establishing the DQ match before transplantation to define immunologic risk.
Imperial College Kidney and Transplant Centre, Hammersmith Hospital, London, UK. Michelle.Willicombe@imperial.nhs.uk
Michelle
M
Willicombe
Paul
P
Brookes
Ruhena
R
Sergeant
Eva
E
Santos-Nunez
Corinna
C
Steggar
Jack
J
Galliford
Adam
A
McLean
Terence H
TH
Cook
Tom
T
Cairns
Candice
C
Roufosse
David
D
Taube
D006084:Graft Rejection / Q000209:etiology*; D006085:Graft Survival; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D007674:Kidney Diseases / Q000209:etiology*; D007678:Kidney Glomerulus / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D015810:Linkage Disequilibrium; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007518:Isoantibodies