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1.
De novo donor‐specific anti‐HLA antibodies mediated rejection in liver‐transplant patients
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Arnaud Del Bello Nicolas Congy‐Jolivet Marie Danjoux Fabrice Muscari Laurence Lavayssière Laure Esposito Isabelle Cardeau‐Desangles Joëlle Guitard Gaëlle Dörr David Milongo Bertrand Suc Jean Pierre Duffas Laurent Alric Christophe Bureau Céline Guilbeau‐Frugier Lionel Rostaing Nassim Kamar 《Transplant international》2015,28(12):1371-1382
The incidence and consequences of de novo donor‐specific anti‐HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver‐transplant patients, without preformed anti‐HLA DSAs, were tested for anti‐HLA antibodies, with single‐antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver‐enzyme levels until the last follow‐up, that is, 34 (1.5–77) months. Twenty‐one patients (14%) developed de novo DSAs. Of these, five patients had C1q‐binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody‐mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B‐cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient‐ and graft‐survival rates did not differ between patients with and without DSAs. In conclusion, liver‐transplant patients with liver abnormalities should be screened for DSAs and AMR. 相似文献
2.
Sevda Hassan Fiona Regan Colin Brown Andrea Harmer Nicky Anderson Hannah Beckwith Candice A. Roufosse Eva Santos‐Nunez Paul Brookes David Taube Michelle Willicombe 《American journal of transplantation》2019,19(6):1720-1729
De novo HLA donor‐specific antibodies (DSA) following transplantation are associated with alloimmune injury and allograft failure. Blood transfusions are allogeneic, and when given posttransplant (PTBT) they may independently increase the risk of HLA antibody development. This study aims to analyze the development of HLA transfusion‐specific antibodies (TSA) to blood donors of transfusions given posttransplant and examine the impact on clinical outcomes. A total of 244 blood donors of transfusions received by 86 transplant patients (46 who developed a DSA post transfusion and 40 who remained DSA negative) were HLA typed. De novo TSA developed against 150/244 (61.5%) blood donors. In 70/150 (46.7%) cases the TSA was of shared HLA antibody specificity with a DSA response in the recipient (DSA+ = TSA+). This occurred when there was a greater overall HLA match between the blood and transplant donor. DSA+ = TSA+ patients had increased risk of allograft failure (P = .0025) and AMR (P = .02) compared with the DSA+ ≠ TSA+ patients. To conclude, PTBT may elicit de novo HLA antibodies. Enhanced HLA matching between the blood and transplant donor is more likely to result in a DSA and TSA of shared antibody specificities. Transfusion avoidance or the use of HLA matched or selected blood may reduce this risk and improve outcomes. 相似文献
3.
Presentation and Outcomes of C4d‐Negative Antibody‐Mediated Rejection After Kidney Transplantation
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B. J. Orandi N. Alachkar E. S. Kraus F. Naqvi B. E. Lonze L. Lees K. J. Van Arendonk C. Wickliffe S. M. Bagnasco A. A. Zachary D. L. Segev R. A. Montgomery 《American journal of transplantation》2016,16(1):213-220
The updated Banff classification allows for the diagnosis of antibody‐mediated rejection (AMR) in the absence of peritubular capillary C4d staining. Our objective was to quantify allograft loss risk in patients with consistently C4d‐negative AMR (n = 51) compared with C4d‐positive AMR patients (n = 156) and matched control subjects without AMR. All first‐year posttransplant biopsy results from January 2004 through June 2014 were reviewed and correlated with the presence of donor‐specific antibody (DSA). C4d‐negative AMR patients were not different from C4d‐positive AMR patients on any baseline characteristics, including immunologic risk factors (panel reactive antibody, prior transplant, HLA mismatch, donor type, DSA class, and anti‐HLA/ABO‐incompatibility). C4d‐positive AMR patients were significantly more likely to have a clinical presentation (85.3% vs. 54.9%, p < 0.001), and those patients presented substantially earlier posttransplantation (median 14 [interquartile range 8–32] days vs. 46 [interquartile range 20–191], p < 0.001) and were three times more common (7.8% vs 2.5%). One‐ and 2‐year post–AMR‐defining biopsy graft survival in C4d‐negative AMR patients was 93.4% and 90.2% versus 86.8% and 82.6% in C4d‐positive AMR patients, respectively (p = 0.4). C4d‐negative AMR was associated with a 2.56‐fold (95% confidence interval, 1.08–6.05, p = 0.033) increased risk of graft loss compared with AMR‐free matched controls. No clinical characteristics were identified that reliably distinguished C4d‐negative from C4d‐positive AMR. However, both phenotypes are associated with increased graft loss and thus warrant consideration for intervention. 相似文献
4.
K. Bächler P. Amico G. Hönger D. Bielmann H. Hopfer M. J. Mihatsch J. Steiger S. Schaub 《American journal of transplantation》2010,10(5):1254-1262
Low‐level donor‐specific HLA‐antibodies (HLA‐DSA) (i.e. detectable by single‐antigen flow beads, but negative by complement‐dependent cytotoxicity crossmatch) represent a risk factor for early allograft rejection. The short‐term efficacy of an induction regimen consisting of polyclonal anti‐T‐lymphocyte globulin (ATG) and intravenous immunoglobulins (IvIg) in patients with low‐level HLA‐DSA is unknown. In this study, we compared 67 patients with low‐level HLA‐DSA not having received ATG/IvIg induction (historic control) with 37 patients, who received ATG/IvIg induction. The two groups were equal regarding retransplants, HLA‐matches, number and class of HLA‐DSA. The overall incidence of clinical/subclinical antibody‐mediated rejection (AMR) was lower in the ATG/IvIg than in the historic control group (38% vs. 55%; p = 0.03). This was driven by a significantly lower rate of clinical AMR (11% vs. 46%; p = 0.0002). Clinical T‐cell‐mediated rejection (TCR) was significantly lower in the ATG/IvIg than in the historic control group (0% vs. 50%; p < 0.0001). Within the first year, allograft loss due to AMR occurred in 7.5% in the historic control and in 0% in the ATG/IvIg group. We conclude that in patients with low‐level HLA‐DSA, ATG/IvIg induction significantly reduces TCR and the severity of AMR, but the high rate of subclinical AMR suggests an insufficient control of the humoral immune response. 相似文献
5.
F. Ginevri A. Nocera P. Comoli A. Innocente M. Cioni A. Parodi I. Fontana A. Magnasco A. Nocco A. Tagliamacco A. Sementa P. Ceriolo L. Ghio M. Zecca M. Cardillo G. Garibotto G. M. Ghiggeri F. Poli 《American journal of transplantation》2012,12(12):3355-3362
The emerging role of humoral immunity in the pathogenesis of chronic allograft damage has prompted research aimed at assessing the role of anti‐HLA antibody (Ab) monitoring as a tool to predict allograft outcome. Data on the natural history of allografts in children developing de novo Ab after transplantation are limited. Utilizing sera collected pretransplant, and serially posttransplant, we retrospectively evaluated 82 consecutive primary pediatric kidney recipients, without pretransplant donor‐specific antibodies (DSA), for de novo Ab occurrence, and compared results with clinical–pathologic data. At 4.3‐year follow up, 19 patients (23%) developed de novo DSA whereas 24 had de novo non‐DSA (NDSA, 29%). DSA appeared at a median time of 24 months after transplantation and were mostly directed to HLA‐DQ antigens. Among the 82 patients, eight developed late/chronic active C4d+ antibody‐mediated rejection (AMR), and four C4d‐negative AMR. Late AMR correlated with DSA (p < 0.01), whose development preceded AMR by 1‐year median time. Patients with DSA had a median serum creatinine of 1.44 mg/dL at follow up, significantly higher than NDSA and Ab‐negative patients (p < 0.005). In our pediatric cohort, DSA identify patients at risk of renal dysfunction, AMR and graft loss; treatment started at Ab emergence might prevent AMR occurrence and/or progression to graft failure. 相似文献
6.
Differential effects of donor‐specific HLA antibodies in living versus deceased donor transplant
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E. G. Kamburova B. W. Wisse I. Joosten W. A. Allebes A. van der Meer L. B. Hilbrands M. C. Baas E. Spierings C. E. Hack F. E. van Reekum A. D. van Zuilen M. C. Verhaar M. L. Bots A. C. A. D. Drop L. Plaisier M. A. J. Seelen J. S .F. Sanders B. G. Hepkema A. J. A. Lambeck L. B. Bungener C. Roozendaal M. G. J. Tilanus C. E. Voorter L. Wieten E. M. van Duijnhoven M. Gelens M. H. L. Christiaans F. J. van Ittersum S. A. Nurmohamed N. M. Lardy W. Swelsen K. A. van der Pant N. C. van der Weerd I. J. M. ten Berge F. J. Bemelman A. Hoitsma P. J. M. van der Boog J. W. de Fijter M. G. H. Betjes S. Heidt D. L. Roelen F. H. Claas H. G. Otten 《American journal of transplantation》2018,18(9):2274-2284
The presence of donor‐specific anti‐HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long‐term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement‐dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10‐year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10‐year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10‐year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence. 相似文献
7.
A. Sicard L. Amrouche C. Suberbielle M. Carmagnat S. Candon E. Thervet M. Delahousse C. Legendre L. Chatenoud R. Snanoudj 《American journal of transplantation》2014,14(1):193-201
The detection of preformed donor‐specific alloantibodies (DSA) with multiplex‐bead arrays has led to the common observation that individuals without a history of pregnancy, transfusion or transplantation can have circulating anti‐HLA antibodies of unknown etiology. We retrospectively analyzed the risk of antibody‐mediated rejection (AMR) and graft outcome in 41 kidney transplant recipients with DSA of unknown etiology (DSA cause‐unk) at the time of transplantation. Twenty‐one patients received a posttransplantation desensitization protocol, and 20 received standard immunosuppressive therapy. The mean number of DSA was 1.4 ± 0.8, ranging from 1 to 5. Complement‐dependent cytotoxicity crossmatches were negative for all the patients. Flow cytometry crossmatches were positive in 47.6% of cases. The incidence of acute AMR was 14.6% at 1 year, regardless of the immunosuppressive regimen. No patients experienced graft loss following AMR. At month 12, across the entire population of patients with DSA cause‐unk, the outcomes were favorable: the measured glomerular filtration rate was 63.8 ± 16.4 mL/min/1.73 m2, the screening biopsies showed low frequencies of microvascular inflammation and no transplant glomerulopathy, and graft and patient survival were 100%. In conclusion, patients with DSA cause‐unk are able to mount AMR but have favorable 1‐year outcomes. 相似文献
8.
ABO Antibody Titer and Risk of Antibody‐Mediated Rejection in ABO‐Incompatible Renal Transplantation
A. A. R. Tobian R. S. Shirey R. A. Montgomery W. Cai M. Haas P. M. Ness K. E. King 《American journal of transplantation》2010,10(5):1247-1253
Therapeutic plasma exchange (TPE) preconditioning with immunosuppressive therapy reduces ABO antibody titers, permitting engraftment of ABO‐incompatible (ABO‐I) kidney transplants. The posttransplant predictive role of ABO antibody titers for antibody‐mediated rejection (AMR) is unknown. This retrospective study evaluated 46 individuals who received TPE to permit ABO‐I kidney transplantation. ABO antibody titers were performed using donor‐type indicator red cells. Seven individuals (15.2%) experienced clinical or subclinical AMR. There was no significant difference between recipient blood group, number of pretransplant TPE and baseline titer between those with and without AMR. At 1–2 weeks posttransplant the median titer was 64 (range 4 – 512) among individuals with AMR and 16 (range 2 – 256) among individuals without AMR. Total agglutination reactivity score was significantly higher among individuals with AMR (p = 0.046). The risk of AMR was significantly higher among individuals with an elevated posttransplant titer of ≥64 (p = 0.006). The sensitivity of an elevated posttransplant titer was 57.1% with a specificity of 79.5%. The positive predictive value was 33.3% and the negative predictive value was 91.2%. Most individuals with AMR have an elevated titer, however, the positive predictive value of a high titer for AMR is poor. 相似文献
9.
Allelic and Epitopic Characterization of Intra–Kidney Allograft Anti‐HLA Antibodies at Allograft Nephrectomy
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N. Kamar A. Del Bello C. Guilbeau‐Frugier F. Sallusto L. Esposito G. Dörr A. Blancher N. Congy‐Jolivet 《American journal of transplantation》2017,17(2):420-431
The reasons for the increased incidence of de novo anti–human leukocyte antibody (HLA) donor‐specific antibodies (DSAs) observed after kidney allograft nephrectomy are not fully understood. One advocated mechanism suggests that at graft loss, DSAs are not detected in the serum because they are fixed on the nonfunctional transplant; removal of the kidney allows DSAs to then appear in the blood circulation. The aim of our study was to compare anti‐HLA antibodies present in the serum and in the graft at the time of an allograft nephrectomy. Using solid‐phase assays, anti‐HLA antibodies were searched for in the sera of 17 kidney transplant patients undergoing allograft nephrectomy. No anti‐HLA antibodies were detected in the graft if they were not also detected in the serum. Eleven of the 12 patients who had DSAs detected in their sera also had DSAs detected in the grafts. Epitopic analysis revealed that most anti‐HLA antibodies detected in removed grafts were directed against the donor. In summary, our data show that all anti‐HLA antibodies that were detected in grafts were also detected in the sera. These intragraft anti‐HLA antibodies are mostly directed against the donor at an epitopic level but not always at an antigenic level. 相似文献
10.
Immediate and Catastrophic Antibody‐Mediated Rejection in a Lung Transplant Recipient With Anti–Angiotensin II Receptor Type 1 and Anti–Endothelin‐1 Receptor Type A Antibodies
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《American journal of transplantation》2017,17(2):557-564
Preexisting donor‐specific anti‐HLA antibodies (DSAs) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti‐HLA DSAs. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventriular dysfunction, which required arteriovenous extracorporeal membrane oxygenation. After a brief period of clinical improvement, a rapid deterioration in hemodynamics led to the patient's death on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody‐mediated rejection (AMR), while terminal samples evidenced diffuse capillaritis, blood extravasation, edema, and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin‐1 receptor type A (ETAR) and the angiotensin II receptor type 1 (AT1R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose after transplantation. These data suggest that preexisting anti‐ETAR and anti‐AT1R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient. 相似文献
11.
Posttransplant reduction in preexisting donor‐specific antibody levels after belatacept‐ versus cyclosporine‐based immunosuppression: Post hoc analyses of BENEFIT and BENEFIT‐EXT
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R. A. Bray H. M. Gebel R. Townsend M. E. Roberts M. Polinsky L. Yang H.‐U. Meier‐Kriesche C. P. Larsen 《American journal of transplantation》2018,18(7):1774-1782
BENEFIT and BENEFIT‐EXT were phase III studies of cytotoxic T‐cell crossmatch–negative kidney transplant recipients randomized to belatacept more intense (MI)‐based, belatacept less intense (LI)‐based, or cyclosporine‐based immunosuppression. Following study completion, presence/absence of HLA‐specific antibodies was determined centrally via solid‐phase flow cytometry screening. Stored sera from anti‐HLA–positive patients were further tested with a single‐antigen bead assay to determine antibody specificities, presence/absence of donor‐specific antibodies (DSAs), and mean fluorescent intensity (MFI) of any DSAs present. The effect of belatacept‐based and cyclosporine‐based immunosuppression on MFI was explored post hoc in patients with preexisting DSAs enrolled to BENEFIT and BENEFIT‐EXT. In BENEFIT, preexisting DSAs were detected in 4.6%, 4.9%, and 6.3% of belatacept MI‐treated, belatacept LI‐treated, and cyclosporine‐treated patients, respectively. The corresponding values in BENEFIT‐EXT were 6.0%, 5.7%, and 9.2%. In both studies, most preexisting DSAs were of class I specificity. Over the first 24 months posttransplant, a greater proportion of preexisting DSAs in belatacept‐treated versus cyclosporine‐treated patients exhibited decreases or no change in MFI. MFI decline was more apparent with belatacept MI‐based versus belatacept LI‐based immunosuppression in both studies and more pronounced in BENEFIT‐EXT versus BENEFIT. Although derived post hoc, these data suggest that belatacept‐based immunosuppression decreases preexisting DSAs more effectively than cyclosporine‐based immunosuppression. 相似文献
12.
Eculizumab Salvage Therapy for Antibody‐Mediated Rejection in a Desensitization‐Resistant Intestinal Re‐Transplant Patient
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J. Fan P. Tryphonopoulos A. Tekin S. Nishida G. Selvaggi A. Amador J. Jebrock D. Weppler D. Levi R. Vianna P. Ruiz A. Tzakis 《American journal of transplantation》2015,15(7):1995-2000
The presence of elevated calculated panel reactive antibody (cPRA) and anti‐HLA donor specific antibodies (DSA) are high risk factors for acute antibody‐mediated rejection (AAMR) in intestinal transplantation that may lead to graft loss. Eculizumab has been used for the treatment of AAMR in kidney transplantation of sensitized patients that do not respond to other treatment. Here, we report a case where eculizumab was used to treat AAMR in a desensitization‐resistant intestinal re‐transplant patient. A male patient lost his intestinal graft to AAMR 8.14 years after his primary transplant. He received a second intestinal graft that had to be explanted a month later due to refractory AAMR. The patient remained highly sensitized despite multiple treatments. He received a multivisceral graft and presented with severe AAMR on day 3 posttransplantation. The AAMR was successfully treated with eculizumab. The patient presently maintains an elevated cPRA level above 90% but his DSAs have decreased from 18 000 MFI (mean fluorescent intensity) to below the positive cut‐off value of 3000 MFI and remains rejection free with a 2‐year follow‐up since his multivisceral transplant. Eculizumab offers an alternative to treat AAMR in intestinal transplantation in desensitization‐resistant patients. 相似文献
13.
Reduction of Extended‐Release Tacrolimus Dose in Low‐Immunological‐Risk Kidney Transplant Recipients Increases Risk of Rejection and Appearance of Donor‐Specific Antibodies: A Randomized Study
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P. Gatault N. Kamar M. Büchler C. Colosio D. Bertrand A. Durrbach L. Albano J. Rivalan Y. Le Meur M. Essig N. Bouvier C. Legendre B. Moulin A.‐E. Heng P.‐F. Weestel J. Sayegh B. Charpentier L. Rostaing E. Thervet Y. Lebranchu 《American journal of transplantation》2017,17(5):1370-1379
The aim of this study (ClinicalTrials.gov, NCT01744470) was to determine the efficacy and safety of two different doses of extended‐release tacrolimus (TacER) in kidney transplant recipients (KTRs) between 4 and 12 mo after transplantation. Stable steroid‐free KTRs were randomized (1:1) after 4 mo: Group A had a 50% reduction in TacER dose with a targeted TacER trough level (C0) >3 μg/L; group B had no change in TacER dose (TacER C0 7–12 μg/L). The primary outcome was estimated GFR at 1 year. Of 300 patients, the intent‐to‐treat analysis included 186 patients (group A, n = 87; group B, n = 99). TacER C0 was lower in group A than in group B at 6 mo (4.1 ± 2.7 vs. 6.7 ± 3.9 μg/L, p < 0.0001) and 12 mo (5.6 ± 2.0 vs. 7.4 ± 2.1 μg/L, p < 0.0001). Estimated GFR was similar in both groups at 12 mo (group A, 56.0 ± 17.5 mL/min per 1.73 m²; group B, 56.0 ± 22.1 mL/min per 1.73 m²). More rejection episodes occurred in group A than group B (11 vs. 3; p = 0.016). At 1 year, subclinical inflammation occurred more frequently in group A than group B (inflammation score [i] >0: 21.4% vs. 8.8%, p = 0.047; tubulitis score [t] >0: 19.6% vs. 8.7%, p = 0.076; i + t: 1.14 ± 1.21 vs. 0.72 ± 1.01, p = 0.038). Anti‐HLA donor‐specific antibodies appeared only in group A (6 vs. 0 patients, p = 0.008). TacER C0 should be maintained >7 μg/L during the first year after transplantation in low‐immunological‐risk, steroid‐free KTRs receiving a moderate dose of mycophenolic acid. 相似文献
14.
Annabelle Goumard Bndicte Sautenet Elodie Bailly Elodie Miquelestorena‐Standley Barbara Proust Hlne Longuet Lise Binet Christophe Baron Jean‐Michel Halimi Matthias Büchler Philippe Gatault 《Transplant international》2019,32(8):820-830
Depleting induction therapy is recommended in sensitized kidney transplant recipients (KTRs), though the detrimental effect of nondonor‐specific anti‐HLA antibodies is not undeniable. We compared the efficacy and safety of basiliximab and rabbit anti‐thymocyte globulin (rATG) in sensitized KTRs without pre‐existing donor‐specific antibodies (DSAs). This monocentric retrospective study involved all sensitized KTR adults without pre‐existing DSAs (n = 218) who underwent transplantation after June 2007. Patients with basiliximab and rATG therapy were compared for risk of biopsy‐proven acute rejection (BPAR) and a composite endpoint (BPAR, graft loss and death) by univariate and multivariate analysis. Patients with basiliximab (n = 60) had lower mean calculated panel reactive antibody than those with rATG (n = 158; 23.7 ± 24.2 vs. 63.8 ± 32.3, P < 0.0001) and more often received a first graft (88% vs. 54%, P < 0.0001) and a transplant from a living donor (13% vs. 2%, P = 0.002). Risks of BPAR and of reaching the composite endpoint were greater with basiliximab than rATG [HR = 3.63 (1.70–7.77), P = 0.0009 and HR = 1.60 (0.99–2.59), P = 0.050, respectively]. Several adjustments did not change those risks [BPAR: 3.36 (1.23–9.16), P = 0.018; composite endpoint: 1.83 (0.99–3.39), P = 0.053]. Infections and malignancies were similar in both groups. rATG remains the first‐line treatment in sensitized KTR, even in the absence of pre‐existing DSAs. 相似文献
15.
J. D. Smith N. R. Banner I. M. Hamour M. Ozawa A. Goh D. Robinson P. I. Terasaki M. L. Rose 《American journal of transplantation》2011,11(2):312-319
Preformed donor HLA‐specific antibodies are a known indicator for poor patient survival after cardiac transplantation. The role of de novo donor‐specific antibodies (DSA) formed after cardiac transplantation is less clear. Here we have retrospectively analyzed 243 cardiac transplant recipients, measuring HLA antibody production every year after transplantation up to 13 years post‐transplant. Production of de novo DSA was analyzed in patients who had been negative for DSA prior to their transplant. DSA including transient antibodies were associated with poor patient survival (p = 0.0018, HR = 3.198). However, de novo and persistent DSA was strongly associated with poor patient survival (p = 0.0001 HR = 4.351). Although complement fixing persistent DSA correlated with poor patient survival, this was not increased compared to noncomplement fixing persistent DSA. Multivariable analysis indicated de novo persistent DSA to be an independent predictor of poor patient survival along with HLA‐DR mismatch and donor age. Only increasing donor age was found to be an independent risk factor for earlier development of CAV. In conclusion, patients who are transplanted in the absence of pre‐existing DSA make de novo DSA after transplantation which are associated with poor survival. Early and regular monitoring of post‐transplant DSA is required to identify patients at risk of allograft failure. 相似文献
16.
Molecular Assessment of Microcirculation Injury in Formalin‐Fixed Human Cardiac Allograft Biopsies With Antibody‐Mediated Rejection
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B. Afzali E. Chapman M. Racapé B. Adam P. Bruneval F. Gil D. Kim L. Hidalgo P. Campbell B. Sis J. P. Duong Van Huyen M. Mengel 《American journal of transplantation》2017,17(2):496-505
Precise diagnosis of antibody‐mediated rejection (AMR) in cardiac allograft endomyocardial biopsies (EMBs) remains challenging. This study assessed molecular diagnostics in human EMBs with AMR. A set of 34 endothelial, natural killer cell and inflammatory genes was quantified in 106 formalin‐fixed, paraffin‐embedded EMBs classified according to 2013 International Society for Heart and Lung Transplantation (ISHLT) criteria. The gene set expression was compared between ISHLT diagnoses and correlated with donor‐specific antibody (DSA), endothelial injury by electron microscopy (EM) and prognosis. Findings were validated in an independent set of 57 EMBs. In the training set (n = 106), AMR cases (n = 70) showed higher gene set expression than acute cellular rejection (ACR; n = 21, p < 0.001) and controls (n = 15, p < 0.0001). Anti‐HLA DSA positivity was associated with higher gene set expression (p = 0.01). Endothelial injury by electron microscopy strongly correlated with gene set expression, specifically in AMR cases (r = 0.62, p = 0.002). Receiver operating characteristic curve analysis for diagnosing AMR showed greater accuracy with gene set expression (area under the curve [AUC] = 79.88) than with DSA (AUC = 70.47) and C4d (AUC = 70.71). In AMR patients (n = 17) with sequential biopsies, increasing gene set expression was associated with inferior prognosis (p = 0.034). These findings were confirmed in the validation set. In conclusion, biopsy‐based molecular assessment of antibody‐mediated microcirculation injury has the potential to improve diagnosis of AMR in human cardiac transplants. 相似文献
17.
Patrícia Soares de Souza Elias David‐Neto Nicolas Panajotopolous Fabiana Agena Hélcio Rodrigues Carla Ronda Daísa Ribeiro David Jorge Kalil Wiliam Carlos Nahas Maria Cristina Ribeiro de Castro 《Clinical transplantation》2014,28(11):1234-1243
The purpose of this study was to sequentially monitor anti‐HLA antibodies and correlate the results with antibody‐mediated rejection (AMR), graft survival (GS), and graft function (GF). We collected sera from 111 kidney transplant recipients on transplant days 0, 7, 14, 30, 60, 90, 180, and 360 and analyzed PRA levels by ELISA. DSAs were analyzed by single‐antigen beads in rejecting kidneys. At pre‐transplant, 79.3% of the patients were non‐sensitized (PRA = 0%) and 20.7% were sensitized (PRA > 1%). After transplant, patients were grouped by PRA profile: no anti‐HLA antibodies pre‐ or post‐transplant (group HLApre?/post?; n = 80); de novo anti‐HLA antibodies post‐transplant (group HLApre?/post+; n = 8); sensitized pre‐transplant/increased PRA post‐transplant (group HLApre+/post↑; n = 9); and sensitized pre‐transplant/decreased PRA post‐transplant (group HLApre+/post↓; n = 14). De novo anti‐HLA antibodies were detected at 7–180 d. In sensitized patients, PRA levels changed within the first 30 d post‐transplant. Incidence of AMR was higher in HLApre?/post+ and HLApre+/post↑ than in HLApre?/post?, and HLApre+/post↓ (p < 0.001) groups. One‐yr death‐censored GS was 36% in group HLApre+/post↑, compared with 98%, 88% and 100% in groups HLApre?/post?, HLApre?/post+, and HLApre+/post↓, respectively (p < 0.001). Excluding first‐year graft losses, GF and GS were similar among the groups. In conclusion, post‐transplant antibody monitoring can identify recipients at higher risk of AMR. 相似文献
18.
Denis Glotz Graeme Russ Lionel Rostaing Christophe Legendre Gunnar Tufveson Steve Chadban Josep Griny Nizam Mamode Paolo Rigotti Lionel Couzi Matthias Büchler Silvio Sandrini Bradley Dain Mary Garfield Masayo Ogawa Tristan Richard William H. Marks 《American journal of transplantation》2019,19(10):2865-2875
The presence of preformed donor‐specific antibodies in transplant recipients increases the risk of acute antibody‐mediated rejection (AMR). Results of an open‐label single‐arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased‐donor kidney transplants with preformed donor‐specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy‐proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow‐up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24‐70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P < .001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010‐019631‐35). 相似文献
19.
Incidence,characterization, and impact of newly detected donor‐specific anti‐HLA antibody in the first year after pediatric heart transplantation: A report from the CTOTC‐04 study
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A. I. Dipchand S. Webber K. Mason B. Feingold C. Bentlejewski W. T. Mahle R. Shaddy C. Canter E. D. Blume J. Lamour W. Zuckerman H. Diop Y. Morrison B. Armstrong D. Ikle J. Odim A. Zeevi the CTOTC‐ Investigators 《American journal of transplantation》2018,18(9):2163-2174
Data on the clinical importance of newly detected donor‐specific anti‐HLA antibodies (ndDSAs) after pediatric heart transplantation are lacking despite mounting evidence of the detrimental effect of de novo DSAs in solid organ transplantation. We prospectively tested 237 pediatric heart transplant recipients for ndDSAs in the first year posttransplantation to determine their incidence, pattern, and clinical impact. One‐third of patients developed ndDSAs; when present, these were mostly detected within the first 6 weeks after transplantation, suggesting that memory responses may predominate over true de novo DSA production in this population. In the absence of preexisting DSAs, patients with ndDSAs had significantly more acute cellular rejection but not antibody‐mediated rejection, and there was no impact on graft and patient survival in the first year posttransplantation. Risk factors for ndDSAs included common sensitizing events. Given the early detection of the antibody response, memory responses may be more important in the first year after pediatric heart transplantation and patients with a history of a sensitizing event may be at risk even with a negative pretransplantation antibody screen. The impact on late graft and patient outcomes of first‐year ndDSAs is being assessed in an extended cohort of patients. 相似文献
20.
J. Levitsky H. Kaneku C. Jie R. C. Walsh M. Abecassis A. R. Tambur 《American journal of transplantation》2016,16(8):2437-2444
With less ischemia, improved donor selection and controlled procedures, living donor liver transplantation (LDLT) might lead to less HLA donor‐specific antibody (DSA) formation or fewer adverse outcomes than deceased donor liver transplantation (DDLT). Using the multicenter A2ALL (Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study) biorepository, we compared the incidence and outcomes of preformed and de novo DSAs between LDLT and DDLT. In total, 129 LDLT and 66 DDLT recipients were identified as having serial samples. The prevalence of preformed and de novo DSAs was not different between DDLT and LDLT recipients (p = 0.93). There was no association between patient survival and the timing (preformed vs. de novo), class (I vs. II) and relative levels of DSA between the groups; however, preformed DSA was associated with higher graft failure only in DDLT recipients (p = 0.01). De novo DSA was associated with graft failure regardless of liver transplant type (p = 0.005) but with rejection only in DDLT (p = 0.0001). On multivariate analysis, DSA was an independent risk factor for graft failure regardless of liver transplant type (p = 0.017, preformed; p = 0.002, de novo). In conclusion, although similar in prevalence, DSA may have more impact in DDLT than LDLT recipients. Although our findings need further validation, future research should more robustly test the effect of donor type and strategies to mitigate the impact of DSA. 相似文献