HLA-DQ AND -DP ALPHA/BETA CHAIN ANTIBODIES IN RENAL TRANSPLANTATION

In kidney transplantation, current HLA class II matching strategies consider DR antigens only. Both a and b chains of HLA-DQ and -DP heterodimers are polymorphic and can elicit a humoral immune response. Preformed HLA class II donor-speci.c antibodies (DSA) have a deleterious impact on graft outcome and post-transplant development of anti-class II DSA is strongly associated with acute and chronic rejection occurrence. This study was done to investigate the incidence of anti-DQ and -DP antibod­ies in 56 kidney transplant (KTx) recipients who developed HLA class II DSA and 145 HLA class II-positive re-transplant candidates. Antibody characteriza­tion was performed by using Single antigen bead assay (microbeads coated with 29 DQA1/DQB1, 24 DPA1/DPB1 heterodimers besides DRB1/3/4/5, molecules). In the KTx group of patients, incidence of anti-DQ/DP DSA was signi.cantly higher than anti-DR DSA (76% vs. 20%, P < 0.0001); in 3 patients we only found anti-DQA1 DSA. During the follow up period, graft failure occurred in 14 of the 38 (36.8%) patients who only developed anti-DQ and/or -DP DSA. Analyzing speci.city of HLA class II antibodies detected in re-transplant can­didates, 131 of the 145 (90%) patients showed production of anti-DQ and/or anti-DP antibodies. Nineteen percent of these patients had only anti-DQ a/b chain antibodies, 5% had only anti-DP a/b chain antibodies and 7% had both anti-DQ and anti-DP antibodies. It is important to underline that 87% of anti- Histocompatibility DQA1/DQB1 positive patients and 98% of anti-DPA1/DPB1 positive patients developed wide antibody patterns due to the recognition of a "public epitope" of the mismatched donor molecule/s. These data demonstrate the great immunogenicity of mismatched DQA1/DQB1 and DPA1/DPB1 molecules of a kidney transplant and underline the need to consider all the HLA class II molecules in matching strategies especially for re-transplant candidates.