SRTR includes information on all donors, wait-listed transplant candidates, and transplant recipients in the U.S. Thus, rituximab induction in HLA incompatible recipients reduced the incidence and magnitude of HLA antibody rebound, but did not impact DSA elimination, antibody mediated rejection, or 5 year allograft survival when compared to recipients desensitized and transplanted without rituximab. Keywords: rituximab, B cells, HLA antibody, desensitization, kidney transplantation Introduction B cell depletion protocols using rituximab, a chimeric murine/human monoclonal antibody specific for CD20, were developed to treat B cell malignancies(1) but have also been utilized to treat antibody-mediated autoimmune diseases(2, 3) and to prevent or combat humoral rejection in solid organ transplantation(4C7). In transplantation, B cell depletion has been used pre-transplantation in desensitization protocols to reduce HLA sensitization allowing access to transplantation(8C11) and perioperatively to prevent the development of donor-specific HLA antibodies (DSA) or Senkyunolide H to prevent an anamnestic response(6, 12C14). It has also been utilized post-transplant, during active antibody mediated rejection (AMR) to dampen the Senkyunolide H immune response(15C17). The efficacy of desensitization protocols that include rituximab to decrease DSA has been reported in both ABO and HLA live donor incompatible renal transplantation(8, 14,18C23). Kohei et al. also reported a decreased incidence of de novo DSA and chronic AMR among ABO incompatible recipients transplanted with rituximab induction compared to an ABO compatible cohort transplanted without rituximab(24). However, the efficacy of rituximab in preventing post-transplantation DSA rebound and enhancing post-transplantation DSA elimination after desensitization protocols has ARF6 not been analyzed in controlled cohorts. Reports to date have compared patients transplanted with rituximab treatment to Senkyunolide H those that had no or less intensive desensitization treatment. Moreover, a limited number of post-transplant time-points and HLA antibodies were included in previous studies(14, 18,23, 25, 26). This study evaluates the impact of rituximab induction on HLA-specific antibody production in patients undergoing desensitization for HLA incompatible live donor kidney transplantation. Our goal was to gain insight into the efficacy of B cell depletion in preventing the activation and differentiation of HLA specific B cells, particularly in sensitized recipients who may harbor HLA-specific memory B cells. Results We compared the incidence of post-transplant HLA antibody rebound in 50 patients undergoing HLA incompatible transplantation using a desensitization protocol that either did or did not include a single dose of rituximab (375 mg/m2) the day before transplantation. Patient demographics are provided in Table 1 and reflect our practice of using rituximab Senkyunolide H for patients with a higher risk for antibody mediated rejection(27, 28). The 25 patients who received rituximab induction had broader sensitization (mean CPRA = 80% versus 60%, p=0.02), a higher incidence of previous transplants (76% versus 28%, p=0.002) and repeat HLA mismatches (80% versus 0%, p<0.0001). However, the two cohorts had similar DSA levels prior to desensitization and received a similar number of plasmapheresis treatments (Table 1., p= 0.20). Table 1 Patient demographics
RituximabN=25
No RituximabN=25
p value
Recipient Age (mean, SD)41 1548 130.08
Male Gender (No. patients, %)8 (32%)7 (28%)1.0
Previous Txn (No. patients, %)19 (76%)7 (28%)0.002Previous Txn 35 (20%)00.06
HLA-A;B;DR;DQ Mismatch (mean)4.85.00.61
Repeat HLA mismatch (No. patients, %)20 (80%)00.0001
CDC CPRA1 (mean, median)48, 5026, 30.02FCXM CPRA (mean, median)80, 8960, 600.02
Crossmatch Strength: (No. patients)CDC+211.0FCXM+9110.77FCXM?, DSA+14131.0
Number of DSAs2 (mean, median)2.0, 2.01.7, 1.00.59
Donor Age (mean, SD)38 1246 110.03
No. Pre-Transplant Plasmapheresis (mean)3.72.30.08
No. Post-Transplant Plasmapheresis (mean)4.13.90.81
anti-CD25 Induction (No. patients, %)10 (40%)12 (48%)0.78
Thymoglobulin Induction (No. patients, %)15 (60%)13 (52%)0.78 Open in a separate window 1Calculated panel reactive antibody (CPRA) was decided for HLA-specific antibodies of sufficient strength to yield a positive cytotoxicity (CDC) or flow cytometric crossmatch (FCXM). 2Number of donor-specific HLA antibodies (DSAs) prior to desensitization. HLA antibody monitoring within the first 2 weeks post-transplant revealed an increase in DSA for 36% (9 of 25) of rituximab-treated patients and in 44% (11 of 25) of non-treated patients transplanted without rituximab (p = 0.77). Elevated DSA was treated with continued plasmapheresis and low dose IVIg; however, all patients completed desensitization treatments within 2 weeks of transplant. An extended analysis was performed on 256 HLA antibodies (DSA and non-DSA) to examine HLA antibody levels following the cessation of plasmapheresis/IVIg treatments. The percent change, comparing HLA antibody levels prior to desensitization (time zero) to four time points (1, 3, 6, 12 months) post-transplant are plotted in Physique 1. The MFI for each antibody was normalized to the positive control bead value, to.