Prevalence Of Donor-specific Antibodies Research Articles

Frequency of Human Leukocyte Antigens and Donor Specific Antibodies in Long-Term Living Donor Kidney Transplantation

PurposeHLA antibodies have been shown to be associated with late graft loss. In this study, we defined the incidence and profiles of anti-HLA antibodies and their impact on graft outcome in long-term kidney recipients. MethodsThe sera of 118 kidney transplant recipients were screened for anti-HLA antibody presence. The antigen specificity of the detected HLA class I and class II antibodies was identified using a Luminex assay (Luminex Corp, Austin, TX, United States). Presence of donor specific antibodies (DSA) was examined in individuals with anti-HLA antibodies using the Luminex method. ResultsAnti-HLA class I and/or class II antibodies were detected in serum of 16.1% of the kidney transplant patients. The antibodies were directed against HLA class I antigens in 4 patients (21.1%), HLA class II antigens in 9 patients (47.4%), and both class I and class II antigens in 6 patients (31.6%). The overall prevalence of DSA was 10.2%. Anti-HLA antibodies were significantly associated with higher rate of cyclosporine use. Presence of DSA was associated with a lower rate of tacrolimus use, a higher rate of cyclosporine use, and lower donor age. Presence of anti-HLA antibodies was associated with higher acute cellular rejection and higher chronic active humoral rejection rates. Presence of DSA was associated with chronic active humoral rejection. ConclusionThe presence of either HLA antibodies or DSA significantly correlated with lower graft survival, poor transplant function, and proteinuria.

Prevalence of antibodies to lung self-antigens (Kα1 tubulin and collagen V) and donor specific antibodies to HLA in lung transplant recipients and implications for lung transplant outcomes: Single center experience

PurposeFor patients with end stage lung disease, lung transplantation (LT) remains the only definitive treatment option. Long term survival post LT is limited by acute and chronic allograft dysfunction. Antibodies to lung self-antigens Kα1Tubulin and collagen V (autoantibodies) have been implicated in adverse outcomes post LT. The aim of our study was to determine the prevalence of autoantibodies in pre- and post-transplant sera, evaluate the impact on post-transplant outcomes. MethodsIn a prospective observational cohort analysis, 44 patients were enrolled who received LT between 09/01/2014 and 10/31/2015. Pre- and post-transplant sera were analyzed using enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies to collagen I, collagen V, and K-alpha 1 tubulin. The outcome variables are presence of primary graft dysfunction (PGD), cumulative acute cellular rejection (ACR), treatment with pulse steroids for clinical rejection, association with DSA, and onset of Bronchiolitis Obliterans Syndrome (BOS). ResultsIn our cohort, 33 patients (75%) tested positive for the presence of autoantibodies. Pre-transplant autoantibodies were present in 23 patients (70%). Only a small percentage (26%) cleared these antibodies with standard immunosuppression. Some developed de novo post-transplant (n = 10). PGD was observed in 34% of our cohort, however the presence of autoantibodies did not correlate with increase in the incidence or severity of PGD. The prevalence of donor specific antibodies (DSA) in the entire cohort was 73%, with an increased prevalence of DSA noted in the autoantibody positive group (78.7% vs. 54.5%) than in the autoantibody negative group. BOS was observed in 20% of the cohort, with a median time to onset of 291 days' post-transplant. Patients with pre-transplant autoantibodies had a statistically significant decrease in BOS-free survival (p = 0.029 by log-rank test). ConclusionsIn our cohort, we observed a high prevalence of autoantibodies and DSA in lung transplant recipients. Pre-transplant autoantibodies were associated with de novo development of DSA along with a decrease in BOS-free survival. Limitations to our study include the small sample size and single center enrollment, along with limited time for follow-up.

Deleterious impact of C3d-binding donor-specific anti-HLA antibodies after pediatric liver transplantation

BackgroundThe prevalence and clinical impact of anti-HLA donor-specific antibodies (DSA) after liver transplantation (LT) have not been extensively studied, especially in pediatric population. MethodsThe present cross-sectional study included 100 patients who underwent a first LT in childhood. Anti HLA immunization study was performed at a single time point during routine follow-up using Luminex® single antigen tests with classical anti-IgG conjugate and anti-C3d conjugate. ResultsThe main indication for LT was biliary atresia (52%) and median age at LT was 4.6years. The median time between LT and DSA assessment was 7.8years (range 1–21years). DSA was identified in twenty-four patients (24%) after LT, with a prevalence of 8%, 28%, 33%, 50%, respectively 0–5years, 5–10years, 10–15years and >15years after LT. DSA were mainly class II (23/24) with a mean MFI of 9.731±5.489 and 18 (79.3%) were C3d-binding DSA. Multivariate analysis disclosed that time elapsed since LT (p<0.01) and history of fulminant hepatitis (p=0.04) were significantly associated with a higher rate of DSA. Liver function tests (at time of DSA assessment) were not different according to the presence or not of DSA (or C3d-binding DSA). Regarding histology, the DSA group had a higher rate of chronic rejection, cirrhosis and centrilobular fibrosis or cirrhosis. In addition, patients with C3d-binding DSA and high MFI (>10,000) had a significant poorer long-term graft survival (p=0.03). ConclusionIn our pediatric cohort of LT, prevalence of DSA was high and increased regularly with time. Presence of C3d positive-DSA with high MFI was associated with a higher rate of graft loss.

Prevalence of Donor-Specific Antibodies After Pediatric Liver Transplantation: A Meta-Analysis.

Prevalence of Donor-Specific Antibodies After Pediatric Liver Transplantation: A Meta-Analysis.

Prevalence of Donor Specific Antibodies and Its Association With Lung Transplant Outcomes: A Single-Center Experience

Prevalence of Donor Specific Antibodies and Its Association With Lung Transplant Outcomes: A Single-Center Experience

Long-term Clinical Relevance of De Novo Donor-Specific Antibodies After Pediatric Liver Transplantation.

Anti-HLA antibodies and especially donor-specific antibodies (DSA) play a significant role in graft survival after solid organ transplantation. Their impact on long-term survival in adult liver transplantation (LT) is controversial, but they may be a risk factor. The effects of DSA after pediatric LT are still unclear. We performed a retrospective evaluation of DSA in sera from 43 children who had received transplants at our tertiary center. Twenty-four patients had good long-term clinical and laboratory graft function (group 1), whereas 19 LT recipients suffered from histologically confirmed and clinically relevant chronic allograft rejection (group 2); 16 of these have already undergone retransplantation due to graft dysfunction. Inclusion criteria were availability of sera before the first LT to identify preformed antibodies in case of DSA positivity after LT and long-term follow-up at our institution. Sera were analyzed for anti-HLA antibodies using Luminex single antigen beads, where a mean fluorescence intensity value of more than 1500 was considered positive. The prevalence of DSA was 33% for group 1 and 68% for group 2. Antibodies were predominantly HLA class II. Values of mean fluorescence intensity were comparable in both groups. Only one of the DSA+ ve patients from group 1 exhibited preformed antibodies. In conclusion, pediatric patients with chronic rejection revealed a higher rate of de novo DSA, especially of HLA-class II DSA. Further studies are necessary to confirm these data with a larger pediatric cohort.

P894 PROPHYLAXIS OF DE NOVO HEPATITIS B VIRUS INFECTION WITH LAMIVUDINE IN HBsAg-NEGATIVE NAIVE RECIPIENTS OF HEPATITIS B CORE ANTIBODY-POSITIVE LIVERS: A 13-YEAR SINGLE-CENTER EXPERIENCE

Methods: • Patients: Consecutive outpatient LT recipients between January and December 2012 • Reference group G0: – >2-fold increase in liver function tests (LFT) or unexplained fibrosis >7kPa (Fibroscan) – Excluded: ischemic cholangiopathy, HBV, HVC, HVE post LT infections. • Control groups: – G1:primary LT, normal LFT – G2:primary LT, abnormal LFT – G3: HCV post-LT Patients were tested for donor specific antibodies (DSA) (Luminex SA), and the results expressed in MFI. Comparison of prevalence of DSA and MFI between G0 and control groups was made. Results: 91pts including 22 pts in G0 and 31, 19, 16 pts in G1, G2, G3 were investigated 9.6 yrs after LT. Fourteen (18.7%) pts had been re-transplanted. DSA were found in 95.5% in G0, anti class II in all cases, vs 50.9% in G1-G3 (p < 0.001). Prevalences of DSA in G1, G2 and G3 were 45.2, 52.6 and 68.8% (p =0.003), respectively. In pts with DSA, median MFI was 9916 in G0 vs 3443 in G0-G3 (p =0.02). Conclusions: Prevalence of DSA (95%) and MFI in G0 patients are significantly higher than in control groups. This highly suggests a role of AMR in long-term unexplained liver graft dysfunctions. In HCV positive pts, the prevalence of DSA was also found high and raises the issue of HCV as a contributor anti-HLA sensitization.