Pitfall in the interpretation of DQ HLA-antibodies

Abstract

HLA-DQ consist of two polymorphic chains, both contribute to immunization. SAB testing which ignores the DQ α , can lead to erroneous DQ-antibody assignments. Pitfall in the interpretation of DQ antibodies in the cases presented here had declined immunologically compatible transplant and exposed the second one to unnecessary immunesuppression. The first patient was a young male referred for kidney transplantation. HLA-antibodies revealed positive DQ7, DQ8, and DQ9 antibodies. B-Flow cross matches with the three evaluated potential living related donors was positive with donor1, 2 (sister and cousin1) but negative with the (cousin2) donor3. All donor typed DQ8. The negative result with donor3 was unexpected. DQA1∗component was thought to be responsible however, bead reactivity analysis could not rule out contribution of B∗03:02. The possibility of unexpressed DQ8 antigen was not supported by serological and high resolution typing which confirmed DQA1∗ 03:02/DQB1∗03:02 in the first two donors &DQA1∗03:01/DQB1∗03:02 in donor3. As the difference between DQA1∗03:02 and DQA1∗03:01 alleles is outside the antigen recognition site the individual DQA1∗03:01 should not account for different immune response. Furthermore, DQA1∗03:01, DQB1∗03:02 coated beads was positive. Flow PRA class II bead on BD showed positive response to homozygous DQA1∗03:02 beads. The inconclusive results in assessing the immunological risk with the donor3, denied patient transplantation for long time before he underwent uneventful transplant. Patient2 was a lady who had failed first graft from her mother and came for retransplant from her full brother. She had weak DQ2 DSA against her mother who shared this antigen with the brother. The first post retransplant SAB showed elevated DQ2, she was put under close observation despite normal creatinine level. A kidney biopsy was unremarkable in the first time but was C4d focally positive in the second one. She received anti-rejection therapy. HR typing confirmed DQB1∗02:02/DQA1∗02:01 for both donors. Reanalysis of bead reaction revealed the antibody we report was against DQB1∗02:01/DQA∗05:01 allele. The patient is now14 months post transplant with good renal function. In conclusion the results of SAB were not conclusive and misleading in the 2 patients respectively.