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Abstract: Objective: Due to increasing waiting times for deceased donor kidneys, living donor kidney transplantation is increasingly performed in the presence of donor-specific antibodies (DSA). Methods: Twenty-three patients with Luminex-detected DSA were successfully desensitized by anti-CD20 therapy and immunoadsorption (N = 19) or plasmapheresis (N = 4) and received a kidney transplant from a living donor. Twelve of the 23 patients (52%) had a positive CDC and/or ELISA crossmatch result before desensitization. Six patients were negative in CDC as well as ELISA screening but positive in Luminex for DSA. Results: The 23 patients received a median of 8 apheresis treatments before and 5 treatments after transplantation. Induction therapy was performed with either thymoglobulin (N = 11) or basiliximab (N = 12). The 2-year graft survival rate was 100%. At last follow up, a median of 12 months after transplantation, median serum creatinine was 1.42 mg/dL, median MDRD-GFR 59.5 mL/min/1.73 m2, and median urinary protein-to-creatinine ratio 0.12. Ten out of fourteen patients (71%) who had completed the first year after transplantation by the time of analysis had no DSA by day 360. Acute T-cell mediated rejection was diagnosed in one patient (4%), and antibody-mediated changes were found in 5 patients (22%). Four out of these 5 patients showed evidence of persistent (N = 2) or reemerging plus/minus de novo DSA (N = 2) on day 360, and the 2 patients with persistent DSA lost their allograft subsequently on days 750 and 810, respectively. Infectious complications were infrequent. Conclusions: Our previously described treatment algorithm for desensitization of living donor kidney transplant recipients with DSA results in good graft outcomes with a low rate of side effects. [Copyright &y& Elsevier]

In recent studies, semi-selective compared to antigen-specific immunoadsorption (IA) columns showed comparable effectiveness in anti-A/B antibody removal before incompatible living donor kidney transplantation. Semi-selective columns allow a greater number of IA treatments at lower costs. They are also capable of removing potentially harmful human leukocyte antigen alloantibodies. Nevertheless, additional plasma exchange treatments are often necessary to reach the preoperative target titer, most likely due to an inadequate anti-A/B IgM antibody depletion. We compared the effectiveness of immunoglobulin and anti-A/B antibody reduction by different semi-selective (Therasorb Ig-flex, Therasorb Ig-omni5, Immunosorba) and antigen-specific (Glycosorb) IA columns during the desensitization of 63 ABO-incompatible living donor kidney transplant candidates with a total of 375 IA treatments. Fifty-three patients were eventually transplanted. Total IgM reduction during the first IA treatment was significantly greater with the Therasorb Ig-omni5 compared to the Therasorb Ig-flex (mean: −71.3 vs −41.6; p = 0.001) or Immunosorba columns (mean: −71.3 vs −42.8; p = 0.03). During a median of 5.5–6 pre-transplant IA treatments, Therasorb Ig-flex and Therasorb Ig-omni5 columns were equally effective in the reduction of total IgM while both showed superior IgM reduction compared to the Immunosorba columns (Therasorb Ig-flex, mean: −81.2 vs −72.2; p = 0.01; Therasorb Ig-omni5, mean: −88.2 vs −72.2; p = 0.02). IgG reduction was not significantly different between groups. Likewise, anti-A/B IgM antibody reduction (titer Saline) during the first IA treatment was significantly greater with the Therasorb Ig-omni5 compared to the Therasorb Ig-flex (mean titer reduction: −1.9 vs −1.1; p = 0.02) and tended to be greater than with Immunosorba or Glycosorb columns. During a median of 5–6 pre-transplant IA treatments, overall anti-A/B IgM antibody reduction was significantly greater when IA was performed with the Therasorb Ig-flex (mean titer reduction: −3.8 vs −1.3; p < 0.001) or Therasorb Ig-omni5 (mean titer reduction: −4.3 vs −1.3; p = 0.01) compared to the Immunosorba columns with no differences compared to the Glycosorb columns. Again, anti-A/B IgG antibody reduction (titer Coombs) was not significantly different between groups. The semi-selective Therasorb Ig-omni5 device offers potential advantages in reducing total IgM as well as anti-A/B IgM antibodies. [ABSTRACT FROM AUTHOR]

Humoral immunity wanes over time after two-dose BNT162b2 vaccination. Emerging variants of concern, such as the B.1.617.2 (delta) variant, are increasingly responsible for breakthrough infections owing to their higher transmissibility and partial immune escape. Longitudinal data on neutralization against the B.1.617.2 (delta) variant are urgently needed to guide vaccination strategies. In this prospective longitudinal observational study, anti-S1 IgG and surrogate neutralizing antibodies were measured in 234 collected samples from 60 health care workers after two-dose vaccination with BNT162b2 at five different time points over an 8-month period. In addition, antibodies against various severe acute respiratory syndrome coronavirus 2 epitopes, neutralization against wild-type, and cross-neutralization against the B.1.617.2 (delta) variant using a live virus assay were measured 6 weeks (second time point) and 8 months (last time point) after first vaccine dose. Median (interquartile range) anti-S1 IgG, surrogate neutralizing, and receptor-binding domain antibodies decreased significantly from a maximum level of 147 (102–298), 97 (96–98), and 20 159 (19 023–21 628) to 8 (4–13), 92 (80–96), and 15 324 (13 055–17 288) at the 8-month follow-up, respectively (p < 0.001 for all). Neutralization against the B.1.617.2 (delta) variant was detectable in all 36 (100%) participants at 6 weeks and in 50 of 53 (94%) participants 8 months after first vaccine dose. Median (interquartile) ID 50 as determined by a live virus assay decreased from 160 (80–320) to 40 (20–40) (p < 0.001). Although humoral immunity wanes over time after two-dose BNT162b2 vaccination in healthy individuals, most individuals still had detectable neutralizing activity against the B.1.617.2 (delta) variant after 8 months. [ABSTRACT FROM AUTHOR]