Clinical Relevance of Anti-HLA Antibodies Detected by Flow-Cytometry Bead-Based Assays—Single-Center Experience (original) (raw)
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HLA class I donor-specific triplet antibodies detected after renal transplantation
Transplantation Proceedings, 2004
The purpose of this study was to investigate whether IgG, non-donor-specific anti-HLA class I antibodies (HLAabI) detected after renal transplantation recognize immunogenic amino acid triplets expressed on the foreign graft. In addition, we sought to evaluate the effect of these antibodies as well as other posttransplant HLAabI on graft outcome. Posttransplant sera from 264 renal recipients were tested for the presence of IgG HLAabI and HLA class II-specific alloantibodies (HLAabII) by ELISA. The HLAMatchmaker computer algorithm was used to define the HLA class I non-donor-specific antibodies, which seem to recognize immunogenic amino acid triplets. Donor-specific triplet antibodies (DSTRab) were detected in 16 of 22 (72.7%) recipients based on at least one HLA-A orB mismatched antigen with the donor. DSTRab were found either without (n ϭ 7) or with (n ϭ 9) HLA donor-specific antibodies (HLA-DSA). The presence of DSTRab alone in the periphery was associated with acute rejection, whereas the presence of both DSTRab and HLA-DSA was associated with chronic rejection and graft failure.
Nephrology Dialysis Transplantation, 2003
Background. The objective of this study was to evaluate the role of post-transplant donor-specific anti-HLA antibodies (DS-HLA Abs) detected by an ELISA method on long-term graft survival. Methods. The serum pre-upost-transplant profile of anti-HLA Abs was analysed in 71 renal transplant patients by ELISA. The HLA specificity of positive sera was analysed by a different ELISA method. According to the results, patients were classified into two different groups: those who either developed DS-HLA Abs or significantly increased their panel-reactive antibody (PRA) (group A) and those who did not (group B). Results. Thirteen out of 71 patients showed posttransplant DS-HLA Abs and were included in group A, whereas the remaining 58 were placed in group B. The incidence of acute rejection (AR) was significantly higher in group A than in group B (77 vs 10%). In addition, seven out of eight patients from group A had graft loss secondary to AR, whereas one of nine grafts lost in group B was due to AR. When analysing the clinical outcome according to HLA class specificity, only patients with HLA-I Abs lost their grafts due to vascular AR. The remaining patients with HLA-II Abs who lost their grafts also had HLA-I Abs. In four of the eight patients who lost their grafts, DS HLA-I Abs were detected several days before AR.
Clinical implications of anti-HLA antibodies testing in kidney transplantation
portuguese journal of nephrology and hypertension, 2018
Alloantibodies against donor human leukocyte antigens (HLA), termed as donor -specific antibodies (DSA), are one of the most important factors for both early and late kidney allograft dysfunction. In the past, these antibodies were mainly detected through cell -based crossmatch tests. Recently, new techniques such as solid phase immunoassays (SPI) have revealed these antibodies in patient sera with a high degree of detail, previously unimaginable. They have allowed us to accurately determine recipients’ allosensitization status, improve pre-transplant risk assessment with a potential donor and post -transplant alloimmune monitoring. However, the high sensitivity of these new assays has also created areas of uncertainty about their clinical impact. In the pre -transplant setting, the presence of preformed DSA has been associated with an increased risk of antibody -mediated rejection (AMR) and subsequent allograft loss. Nevertheless, several studies have shown that not all DSA are del...
Journal of the American Society of Nephrology, 2005
The involvement of immunologic and nonimmunologic events in long-term kidney allograft failure is difficult to assess. The development of HLA antibodies after transplantation is the witness of ongoing reactivity against the transplant, and several studies have suggested that the presence of HLA antibodies correlates with poor graft survival. However, they have not discriminated between donor-specific (DS) and non-specific (NDS) antibodies. A total of 1229 recipients of a kidney graft, transplanted between 1972 and 2002, who had over a 5-yr period a prospective annual screening for HLA antibodies with a combination of ELISA, complement-dependent cytotoxicity, and flow cytometry tests were investigated; in 543 of them, the screening was complete from transplantation to the fifth year postgrafting. Correlations were established between the presence and the specificity of the antibodies and clinical parameters. A total of 5.5% of the patients had DS, 11.3% had NDS, and 83% had no HLA antibodies after transplantation. NDS antibodies appeared earlier (1 to 5 yr posttransplantation) than DS antibodies (5 to 10 yr). In multivariate analysis, HLA-DR matching, pretransplantation immunization, and acute rejection were significantly associated with the development of both DS and NDS antibodies and also of DS versus NDS antibodies. The presence of either DS or NDS antibodies significantly correlated with lower graft survival, poor transplant function, and proteinuria. Screening of HLA antibodies posttransplantation could be a good tool for the follow-up of patients who receive a kidney transplant and allow immunosuppression to be tailored.
Annals of transplantation, 2018
BACKGROUND Donor-specific antibodies (DSA), directed against human leucocyte antigens (HLA), are associated with increased risk for graft rejection in kidney transplantation. Anti-HLA antibodies detection by Luminex™ present high sensitivity and accuracy, but its interpretation after transplantation is not completely clear. The aim of this study was to evaluate the impact of anti-HLA antibodies, preformed or de novo, on renal function, graft survival, and incidence of antibody-mediated acute rejection (AMR). MATERIAL AND METHODS A retrospective cohort of 86 kidney transplant recipients was divided into 3 groups according to the presence of anti-HLA antibodies before transplantation: donor-specific antibodies (DSA+, n=15), non-DSA (non-DSA, n=39), and negative pre-transplant panel reactive antibodies (PRA) that became positive after transplantation (PRA-, n=22). Forty-nine recipients with negative PRA pre- and post-transplantation were excluded. Antibody specificity and intensity of ...
2017
Les anticorps anti HLA de novo après la transplantation rénale: signification clinique et association avec la fonction du greffon Contexte. La transplantation rénale (TR) est le meilleur traitement de la maladie rénale chronique. Le rejet chronique, cellulaire ou humoral, est toujours présent dans la pathologie du greffon. La technologie Luminex a permis une détection d'anticorps anti HLA (HLA-Ac) spécifiques du donneur (DSA) et du non donneur (non-DSA). Notre travail étudie l'impact des HLA-Ac de novo sur la fonction du greffon. Matériel et méthodes. 50 pts greffés (42 de donneur vivant et 8 de donneur décédé) ont été inclus dans une étude prospective de 12 mois. Les HLA-Ac ont été analysés à l'aide du kit mixte LABScreen au cours des premier et 12ème mois. Selon la présence de HLA-Ac, les pts ont été répartis dans un groupe 1 (HLA +) et le groupe 2 (HLA-). Les groupes ne différaient pas en ce qui concerne le sexe, l'âge, le donneur, l'immunosuppression, la maladie initiale, les rejets, l'incompatibilité HLA, le temps d'ischémie froide et chaude. La créatinine sérique (Cr), DFG (Cockroft Gault) et la ABSTRACT Background. Kidney transplantation (TR) is the best treatment of chronic kidney disease. Chronic cellular and humoral rejections have still major impact on graft survival. Single antigen bead technology enabled detection of donor specific (DSA) and non-donor specific (Non-DSA) anti HLA antibodies (HLA-Ab). Our study investigates the impact of de novo HLA-Ab on graft function (GF) 12 months after TR. Material and methods. Fifty pts with living (42) and deceased donor (8) transplantation were included in a 12-month prospective study. HLA-Ab were analyzed using LABScreen mixed kit in the 1 st and 12 th month after TR. According to the presence of HLA-Ab, pts were divided in group 1 (HLA+) and group 2 (HLA-). Both groups did not differ regarding gender, age, living or deceased donor, immunosuppression, underlying renal disease, rejection episodes, HLA mismatch, cold and warm ischemia time. Serum creatinine (SCr), GFR (Cockroft Gault) and proteinuria (Pr) were analyzed 1 st and 12 th month after TR. Results. HLA-Ab were detected in 17 pts (34%), 5 with DSA (10%) and 12 with Non-DSA (24%). Group 1 has a significant worsening of GFR (SCr increased
Human Immunology, 2009
Whether sensitized patients wait for a compatible crossmatch with a deceased donor, enter a paired exchange program with the hope of finding a compatible living donor, or go through a desensitization protocol depends on a number of factors, not the least of which is the overall philosophy of the transplant center. Centers such as ours take the position that donor-directed antibodies detected by solid phase assays (even those that are "weak") present an unacceptable risk factor to the patient. This philosophy is predicated on the biologic role of the immune system, specifically that antibodies were generated in response to a non-self (allo) antigen and that a successful immune response eliminates that which caused its stimulation. Although obviously an oversimplification, this philosophy mandates a comprehensive evaluation of HLA antibodies in sensitized recipients. This article addresses the challenges and conundrums associated with human leukocyte antigen antibody identification.