All that Glitter is not Gold: Persistent and Strong De Novo Anti-DSA Antibodies at High Titer Could not be Associated with AMR Whether Solid Phase Luminex SA C1q-Binding Assay is Negative in Post-Transplantation

Background: The complement-fixing ability of HLA antibody, irrespective of IgG (median fluorescence intensity) MFI strength could be a key component of clinical outcome. Recently, it has been developed a C1q-SAB assay that identifies complement-fixing HLA antibodies with high sensitivity and specificity. However, there is no consensus and each center determines its own threshold consistent with its transplant practices. This work presents an interesting case of de novo anti-DSA (donor specific antibody) antibodies development in the post-transplant period with a high titer (MFI>15000) in the routine SAB (single antigen beads) assay but not producing acute rejection and with result of C1qSAB being negative. Case Presentation: A 39-year-old-man was transplanted with 2 HLA-A and 1 DR incompatibilities (recipient typing: A*30, *68; B*07. *35; DRB1*10, *14; DQB1*05, -; 2nd donor typing: A*02, *29; B*07, *35; DRB1*01, *13; DQB1*05, *06) (MMs in cursive) and with CDC cross-match negative. He was sensitized to HLA antigens by CDC and LMX (luminex) assays, with one previous transplant (14-years ago) (1st donor: A1, 3; B35, 57; DR7, -; DQ2, 9) (his SAB specificities against 1st donor were Bw4, A9, 25, 32, DR7, 9, 53, DQ2, 3). In the routine 2nd post-transplantation monitoring (9th month 2nd post-TX), we detected anti-2nd donor anti-DSA antibodies A2 (MFI=16000) and A29 (MFI=8000) by Luminex with our patient presenting an optima clinical situation. With these facts, nephrologists in our hospital indicated a renal biopsy which was completely normal, without any evidence of C4d deposits and the current creatinine of < 1.2 mg/dl. The rest of the post transplant course was uncomplicated. In spite of that, the patient was administered plasmapheresis and IVIG. We determined C1q SAB assay and the result was completely negative for A2 and A29 DSA alloantibodies. In C1qSAB assay, antibodies were assigned as ´posible´ when the first increase more than 33% (but at least 400 MFI) over the prior lower MFI bead was observed. Therefore, our patient had high titers of post-transplant DSA antibodies, but these antibodies did not seem to produce allograft injury and were not capable of fixing complement. Conclusion: These data suggest that the determination of C1qSAB is very important to define the capability of anti-DSA antibodies to fixing complement in the post-transplantation period and clarify the treatment procedure.