Impact of COVID-19 pandemic on transplant laboratories: How to mitigate?

A positive flow cytometry crossmatch (FCXM) due to donor specific antibodies (DSA) constitutes a risk for kidney transplantation; such a finding may indicates an unacceptable donor for this patient. However, positive FCXM in the absence of DSA is considered discordant and need further investigations. During COVID-19 pandemic, we observed 22% discordant results out of 445 FCXM performed during eight months period in our laboratory and another 7% were invalid due to high background negative control (NC). No study has addressed the impact of COVID-19 pandemic on FCXM and the overall pre-kidney transplant workups or described a solution to deal with these non-specific reactivities. Herein, we analyzed all FCXM results in SARS-CoV-2 seropositive patients and addressed how this pandemic affected significantly the pre-kidney transplant workups, highlighting both technical and financial implications. We also shared our modified FCXM procedures using dithiotheritol (DTT) sera treatment or blocking donor cells with negative control human serum (NCS) which we found to be successful to abrogate 98% of all discordant FCXM results and to validate all invalid results due to high background NC. In conclusion, COVID-19 pandemic has affected our HLA laboratory significantly by creating many false positive or invalid crossmatch results. Transplant laboratories must consider this before test interpretations and immune risk assessments. We recommend the use of DTT serum treatment to remove nonspecific bindings in the sera of kidney transplant candidates and the use of NCS-blocked donor cells to correct high background when performing FCXM in transplant candidates or donors with recent history of SARS-CoV-2 immunization respectively.

Transplant tourism following the declaration of Istanbul: Poor outcomes and nephrologist dilemma.

AIM: Transplant tourism (TT) violates many international laws and documents. Despite all efforts, TT seems to be increasing. The aim of this study is to review outcomes of recipients of commercially transplanted kidneys since the Declaration of Istanbul. METHODS: All recipients of kidney transplantation done abroad and then returning to our centre, from September 2008 to December 2015, were included (tourists). Demographics and outcomes were collected from patients' charts. All data were compared with all recipients of living donor kidney transplants done at our centre (locals). RESULTS: A total of 86 tourists and 365 locals were included. Both groups had similar age and gender. Re-grafting rates were the same, however, more pre-emptive transplants were done abroad. TT increased over time. Tourists presented early after TT, median 17.5 (IQR 7-30) days, and 47.7% were encountered initially in the emergency department. One-year graft and patient survivals were significantly lower among tourists compared with locals (87.2% vs. 98.0%, P < 0.001 and 90.7% vs. 98.0%, P < 0.001, respectively). Tourists had a significantly higher rate of acute cellular rejection (19.8% vs. 7.1%, P < 0.001), and they sustained significantly higher rates of serious viral, bacterial and fungal infections compared with the locals. CONCLUSION: Transplant tourism seems to be increasing despite international condemnation and efforts to stop it. Outcomes are significantly worse when compared to local transplant recipients. Concerted effort is needed to better inform patients about the ethical and physical harms related to TT, and to point them towards ethically sound and medically safer alternatives.

The dilemma of DQ HLA-antibodies.

Accurate identification of antibody reactivity against HLA-DQ antigens was difficult by using the old serological assays because of the strong linkage disequilibrium between HLA-DR and HLA-DQ (the usual inheritance of a certain HLA-DR molecule that ties together with the same DQ molecule within a racial group). The accurate and precise identifications of anti-HLA-antibodies of DQ specificities were made possible with the introduction of multiplex-bead arrays (Luminex), using single antigen bead (SAB) assay. The SAB assay is also considered today to be the most sensitive and specific method for alloimmunization assessment even for the low titer anti-HLA-antibodies. However, it is becoming clear that the detection of the HLA antibodies by SAB is not absolutely perfect due to the variation in densities, conformations and orientations of the antigen coated beads. Unlike HLA-DR, the HLA-DQ antigens are made of two polymorphic chains, both (alpha and beta chains) can contribute to the process of immunization individually or jointly. Routine SAB testing approach, which assigns the specificities based on beta chains and ignores the contribution of the DQα chains, can lead to erroneous DQ-antibody assignments. Therefore, it is important to recognize both the peculiarity of the HLA-DQ antigens as well as the nature of the assay format used in order to reach the correct antibody assignments. Erroneous donor specific antibodies (DSA) assignment may lead to denial of an otherwise immunologically compatible organ transplant, or exposing transplant recipients to unnecessary investigations or immunosuppression. The following two patients presented with HLA-antibodies against DQ antigens (anti-DQ-Abs) highlight these two scenarios.