Marginal Impact of Tocilizumab Monotherapy on Anti-HLA Alloantibodies in Highly Sensitized Kidney Transplant Candidates.

BACKGROUND: Highly HLA-sensitized kidney transplant candidates are difficult to desensitize, which reduces their chances of receiving a transplant. METHODS: We administered tocilizumab as a monotherapy (8 mg/kg once a mo) to 14 highly sensitized kidney transplant candidates. Highest mean fluorescence intensities of anti-HLA antibodies obtained before and after tocilizumab administration were compared from raw and diluted sera. RESULTS: The administration of tocilizumab significantly reduced dominant anti-HLA antibody sensitization. However, this decrease in mean fluorescence intensities was minor compared with the initial values. CONCLUSIONS: Tocilizumab as a monotherapy was not sufficient to allow highly sensitized kidney-transplant candidates to undergo transplantation and, therefore, was not an effective desensitization method.

Treatment of antibody-mediated rejection with double-filtration plasmapheresis, low dose IVIg plus rituximab after kidney transplantation.

Antibody-mediated rejection (ABMR) at early or late post-transplantation remains challenging. We performed a single-center single-arm study where four cases of acute ABMR and nine cases of chronic active ABMR (defined by Banff classification) were treated with double-filtration plasmapheresis (two cycles of three consecutive daily sessions with a 4-day gap between). At the end of the third and sixth DFPP sessions, the patients received rituximab 375 mg/m2 . After a median follow-up of 1078 (61-1676) days, kidney-allograft survival was 50%. Before DFPP/rituximab therapy, the median donor-specific alloantibody (DSA) mean fluorescence intensity (MFI) was 9160 (4000-15 400); 45 days (D45) later it had significantly decreased to 7375 (215-18 100) (P = .018). In addition, at one-year (Y1) post-therapy, MFI had decreased further, that is, 4060 (400-7850) (P = .001). In two patients, DSA MFIs decreased and remained below 2000. The slope of estimated glomerular-filtration rate within the 6 months preceding intervention was -1.18 mL/min/month and remained unchanged at -1.29 mL/min/month within the year after intervention. Proteinuria remained unchanged. Baseline Banff scores on repeat allograft biopsies (post-therapy D45, Y1) did not show any improvement. Side-effects were mild to moderate. We conclude that the combined DFPP/rituximab significantly decreased DSAs in ABMR kidney-transplant recipients but did not improve renal function or renal histology at 1-year follow-up.

Systematic Screening Using Luminex for De Novo C3d Fixing of Class II Donor-Specific Antibodies Is Correlated With Luminex Mean Fluorescence Intensity in Renal Transplant Patients.

OBJECTIVES: Chronic antibody-mediated rejection is the main cause of late kidney graft loss. The presence of donor-specific antibodies in the serum is the main criterion for this diagnosis. Single antigen Luminex assays can identify donor-specific antibodies, and semiquantitative estimates of antibodies can be assessed using mean fluorescence intensity. Recent data have shown that patients whose donor-specific antibodies fix C3d have worse clinical outcomes, implying that C3d-specific Luminex assays may provide useful prognostic data. MATERIALS AND METHODS: We compared C3d donor-specific antibodies with standard immunoglobulin G donor-specific antibody mean fluorescence intensities in a cohort of patients with de novo class II donor-specific antibodies and analyzed subsequent graft survival. The included kidney graft recipients received transplants between 2005 and 2015 and had developed de novo class II donor-specific antibodies. Serum was tested using the standard single antigen Luminex technique and the C3d-fixing antibody-detection system (Immucor, Herentals, Belgium). RESULTS: In our patient cohort, 41/924 patients (4.4%) developed class II donor-specific antibodies, and 65 serum samples were analyzed (at baseline and follow-up). Among these samples, 43 (66%) were negative for C3d donor-specific antibodies. A mean fluorescence intensity threshold of 9000 in the single antigen Luminex assay discerned all negative (from positive) C3d donor-specific antibodies, even when all single-bead results were taken into account. Sixteen patients (39%) had poor outcomes (ie, either creatinine levels had doubled or they had lost their graft) over the median follow-up of 5 years. C3d results were significantly associated with graft survival (P = .04). We found a strong correlation between C3d-fixing antibody positivity and mean fluorescence intensity strength in the setting of de novo class II donor-specific antibodies. CONCLUSIONS: These results further reinforce the paradigm that the higher the mean fluorescence intensity, the more complement activation occurs. Routine C3d testing is thus unnecessary in this setting.