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1.
Aleksandar Senev Maarten Coemans Evelyne Lerut Vicky Van Sandt Liesbeth Daniëls Dirk Kuypers Ben Sprangers Marie‐Paule Emonds Maarten Naesens 《American journal of transplantation》2019,19(3):763-780
In this cohort study (n = 935 transplantations), we investigated the phenotype and risk of graft failure in patients with histological criteria for antibody‐mediated rejection (ABMR) in the absence of circulating donor‐specific anti‐human leukocyte antigen (HLA) antibodies (DSA), and compared this to patients with definite ABMR and HLA‐DSA‐positivity. The histological picture did not differ between HLA‐DSA‐positive (n = 85) and HLA‐DSA‐negative (n = 123) cases of ABMR histology, apart from increased complement split product 4d (C4d) deposition in the peritubular capillaries in HLA‐DSA‐positive cases. Histology of ABMR without HLA‐DSA was more transient than DSA‐positive ABMR, and patients with ABMR histology without HLA‐DSA had graft survival superior to that of HLA‐DSA‐positive patients, independent of concomitant T cell–mediated rejection (38.2%) or borderline changes (17.9%). Multivariate analysis showed that the risk of graft failure was not higher in patients with histological picture of ABMR (ABMRh) in the absence of HLA‐DSA, compared to patients without ABMRh. Despite an association between C4d deposition and HLA‐DSA‐positivity, using C4d deposition as alternative for the DSA criterion in the diagnosis of ABMR, as proposed in Banff 2017, did not contribute to the prognosis of graft function and graft failure. We concluded that biopsies with ABMRh but without detectable HLA‐DSA represent a distinct, often transient phenotype with superior allograft survival. 相似文献
2.
Functional Fc gamma receptor gene polymorphisms and donor‐specific antibody‐triggered microcirculation inflammation 下载免费PDF全文
M. L. Arnold A. Kainz L. G. Hidalgo F. Eskandary N. Kozakowski M. Wahrmann H. Haslacher R. Oberbauer A. Heilos B. M. Spriewald P. F. Halloran G. A. Böhmig 《American journal of transplantation》2018,18(9):2261-2273
3.
Lee S. Nguyen Guillaume Coutance Joe‐Elie Salem Salima Ouldamar Guillaume Lebreton Alain Combes Julien Amour Mojgan Laali Pascal Leprince Shaida Varnous 《American journal of transplantation》2019,19(4):1160-1167
Gender‐difference regarding antibody‐mediated rejection (AMR) after heart transplantation has been described. However, no study accounted for the presence of preformed donor‐specific antibodies (pfDSA), a known risk factor of AMR, more common among women than men. In a single‐institution 6‐year cohort (2010‐2015), time to AMR was assessed, comparing men with women by survival analysis with a 1‐year death‐censored follow‐up. All AMRs were biopsy proven. Confounding variables that were accounted for included mean intensity fluorescence (MFI) of pfDSA, recipient age, HLA‐, size‐ and sex‐mismatch. 463 patients were included. Overall incidence of AMR was 10.3% at 1 year. After adjusting for confounding variables, independent risk factors of AMR were female recipient gender (adjusted hazard‐ratio [adj. HR] = 1.78 [1.06‐2.99]), P = .03) and the presence of pfDSA (adj. HR = 3.20 [1.80‐5.70], P < .001). This association remained significant when considering pfDSA by their MFI; female recipient gender had an adj. HR = 2.2 (P = .026) and MFI of pfDSA (per 1 MFI‐increase) adj. HR = 1.0002 (P < .0001). In this cohort, women were at higher risk of AMR than men and this risk increase was additive to that of pfDSA. These findings may suggest a gender‐related difference in the severity of pfDSA. 相似文献
4.
Jonathan Visentin Thomas Bachelet Olivier Aubert Arnaud Del Bello Charlie Martinez Frdric Jambon Gwendaline Guidicelli Mamy Ralazamahaleo Charlne Bouthemy Marine Cargou Nicolas Congy‐Jolivet Thoa Nong Jar‐How Lee Rebecca Sberro‐Soussan Lionel Couzi Nassim Kamar Christophe Legendre Pierre Merville Jean‐Luc Taupin 《American journal of transplantation》2020,20(5):1365-1374
Anti‐denatured HLA‐Cw antibodies are highly prevalent, whereas anti‐native HLA‐Cw antibodies seem to lead to random flow cytometry crossmatch results. We aimed to reassess crossmatch prediction for anti‐HLA‐Cw using 2 types of single antigen flow beads (classical beads and beads with diminished expression of denatured HLA), and to compare the pathogenicity of preformed anti‐denatured and anti‐native HLA‐Cw antibodies in kidney transplantation. We performed 135 crossmatches with sera reacting against donor HLA‐Cw (classical beads fluorescence ≥500); only 20.6% were positive. Forty‐three (31.6%) were anti‐denatured HLA antibodies (beads with diminished expression of denatured HLA fluorescence <300); all were crossmatch negative. The correlation between classical beads fluorescence and the crossmatch ratio was low (ρ = 0.178), and slightly higher with beads with diminished expression of denatured HLA (ρ = 0.289). We studied 52 kidney recipients with preformed anti‐HLA‐Cw donor‐specific antibodies. Those with anti‐native HLA antibodies experienced more acute and chronic antibody‐mediated rejections (P = .006 and .03, respectively), and displayed a lower graft survival (P = .04). Patients with anti‐native HLA‐Cw antibodies more frequently had previous sensitizing events (P < .000001) or plausibility of their antibody profile according to known anti‐native HLA‐Cw eplets (P = .0001). Anti‐native but not anti‐denatured HLA‐Cw antibodies are deleterious, which underscores the need for reagents with diminished expression of denatured HLA. 相似文献
5.
Stanley C. Jordan Noriko Ammerman Jua Choi Edmund Huang Alice Peng Supreet Sethi Reiad Najjar Irene Kim Mieko Toyoda Sanjeev Kumar Kathlyn Lim Ashley Vo 《American journal of transplantation》2020,20(Z4):42-56
Modification of pathogenic antibodies and their effector functions in autoimmune diseases or use of B cell/plasma cell‐directed anticancer therapies have illuminated the biologic relevance of B cells, plasma cells (PCs), and pathogenic antibodies and complement in alloimmunity. They have also rejuvenated interest in how B cells mediate multiple effector functions that include antibody production, antigen presentation to T cells, costimulation, and the production of immune stimulating and immune modulatory cytokines that drive dysfunctional immune responses. Current methods to reduce alloantibodies are only modestly successful. Rituximab is used for desensitization and antibody‐mediated rejection (AMR) treatment by targeting CD20 found on B‐lymphocytes. However, PCs do not express CD20, likely explaining the limited success of this approach. Intravenous immunoglobulin and plasmapheresis (PLEX) have limited success due to antibody rebound. Despite attempts to develop tolerable therapeutics for management of AMR, none, to date, have been universally accepted or obtained Food and Drug Administration approval. Lack of approved therapeutics often results in patients having a much shorter graft survival due to AMR. Repurposing drugs from autoimmunity and cancer immunotherapy has rapidly yielded important advancements in the care of AMR patients. Here we discuss emerging therapeutics aimed at prevention and treatment of AMR. 相似文献
6.
Edmund Huang Supreet Sethi Alice Peng Reiad Najjar James Mirocha Mark Haas Ashley Vo Stanley C. Jordan 《American journal of transplantation》2019,19(6):1663-1670
Donor‐derived cell‐free DNA (dd‐cfDNA) became Medicare reimbursable in the United States in October 2017 for the detection of rejection in kidney transplant recipients based on results from its pivotal validation trial, but it has not yet been externally validated. We assessed 63 adult kidney transplant recipients with suspicion of rejection with dd‐cfDNA and allograft biopsy. Of these, 27 (43%) patients had donor–specific antibodies and 34 (54%) were found to have rejection by biopsy. The percentage of dd‐cfDNA was higher among patients with antibody–mediated rejection (ABMR; median 1.35%; interquartile range [IQR]: 1.10%‐1.90%) compared to those with no rejection (median 0.38%, IQR: 0.26%‐1.10%; P < .001) and cell–mediated rejection (CMR; median: 0.27%, IQR: 0.19%‐1.30%; P = .01). The dd‐cfDNA test did not discriminate patients with CMR from those without rejection. The area under the ROC curve (AUC) for CMR was 0.42 (95% CI: 0.17‐0.66). For ABMR, the AUC was 0.82 (95% CI: 0.71‐0.93) and a dd‐cfDNA ≥0.74% yielded a sensitivity of 100%, specificity 71.8%, PPV 68.6%, and NPV 100%. The dd‐cfDNA test did not discriminate CMR from no rejection among kidney transplant recipients, although performance characteristics were stronger for the discrimination of ABMR. 相似文献
7.
The role of C4d deposition in the diagnosis of antibody‐mediated rejection after lung transplantation 下载免费PDF全文
P. R. Aguilar D. Carpenter J. Ritter R. D. Yusen C. A. Witt D. E. Byers T. Mohanakumar D. Kreisel E. P. Trulock R. R. Hachem 《American journal of transplantation》2018,18(4):936-944
Antibody‐mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single‐center study to characterize cases of C4d‐negative probable AMR and to compare these to cases of definite (C4d‐positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d‐positive and 45 (62%) were C4d‐negative. The two groups had a similar clinical presentation, and although more patients in the C4d‐positive group had neutrophilic capillaritis (54% vs. 29%, P = .035), there was no significant difference in the presence of other histologic findings. Despite aggressive antibody‐depleting therapy, 19 of 73 (26%) patients in the overall cohort died within 30 days, but there was no significant difference in freedom from chronic lung allograft dysfunction (CLAD) or survival between the two groups. We conclude that AMR may cause allograft failure, but that the diagnosis requires a multidisciplinary approach and a high index of suspicion. C4d deposition does not appear to be a necessary criterion for the diagnosis, and although some cases may respond initially to therapy, there is a high incidence of CLAD and poor survival after AMR. 相似文献
8.
Carrie A. Schinstock Ruth Sapir‐Pichhadze Maarten Naesens Ibrahim Batal Serena Bagnasco Laurine Bow Patricia Campbell Marian C. Clahsen‐van Groningen Matthew Cooper Emanuele Cozzi Darshana Dadhania Fritz Diekmann Klemens Budde Fritz Lower Babak J. Orandi Ajda T. Rowshani Lynn Cornell Edward Kraus 《American journal of transplantation》2019,19(1):123-131
The aim of this study was to determine how the Banff antibody‐mediated rejection (ABMR) classification for kidney transplantation is interpreted in practice and affects therapy. The Banff Antibody‐Mediated Injury Workgroup electronically surveyed clinicians and pathologists worldwide regarding diagnosis and treatment for 6 case‐based scenarios. The participants' (95 clinicians and 72 renal pathologists) assigned diagnoses were compared to the Banff intended diagnoses (reference standard). The assigned diagnoses and reference standard differed by 26.1% (SD 28.1%) for pathologists and 34.5% (SD 23.3%) for clinicians. The greatest discordance between the reference standard and clinicians' diagnosis was when histologic features of ABMR were present but donor‐specific antibody was undetected (49.4% [43/87]). For pathologists, the greatest discordance was in the case of acute/active ABMR C4d staining negative in a positive crossmatch transplant recipient (33.8% [23/68]). Treatment approaches were heterogeneous but linked to the assigned diagnosis. When acute/active ABMR was diagnosed by the clinician, treatment was recommended 95.3% (SD 18.4%) of the time vs only 77.7% (SD 39.2%) of the time when chronic active ABMR was diagnosed (P < .0001). In conclusion, the Banff ABMR classification is vulnerable to misinterpretation, which potentially has patient management implications. Continued efforts are needed to improve the understanding and standardized application of ABMR classification in the transplant community. 相似文献
9.
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
10.
Kevin Louis Alexandre Hertig Jean‐Luc Taupin David Buob Matthieu Jamme Isabelle Brocheriou Yosu Luque Chantal Jouanneau Nacera Ouali Marie Audouin Eric Rondeau Yi‐Chun Xu‐Dubois 《American journal of transplantation》2019,19(9):2434-2445
Graft microvasculature is a major target of donor‐specific antibodies (DSA) and endothelial damage is direct evidence of antibody‐mediated rejection (ABMR). Using immunohistochemistry, we analyzed the expression of three microvascular endothelial activation markers (fascin, vimentin, and hsp47), suggestive of endothelial‐to‐mesenchymal transition (EndMT) in 351 graft biopsies from 248 kidney recipients, with concomitant screening of circulating antihuman leukocyte antigen (HLA) DSA at the time of the biopsy. The factors associated with EndMT marker expression were DSA and the presence of microvascular inflammation (MI). EndMT expressing grafts had significantly more allograft loss compared to EndMT negative grafts (P < .0001). The expression of EndMT markers positively correlated with anti‐HLA DSA class II mean fluorescence intensity (MFI) levels and especially identified DQ and DR antibodies as being more closely associated with microvascular injury. Moreover, only DSA linked to positive EndMT score affected allograft survival, regardless of DSA MFI levels or presence of C4d deposition. Thus, EndMT markers could represent a clinically relevant tool for early identification of ongoing endothelial injury, harmful DSA, and patients at high risk for allograft failure. 相似文献
11.
Carolyn Glass Yasmeen M. Butt Sefik Tunc Gokaslan Jose R. Torrealba 《American journal of transplantation》2019,19(11):3149-3154
Pathologic antibody‐mediated rejection (pAMR) occurs in 10% of cardiac transplant patients and is associated with increased mortality. The endomyocardial biopsy remains the primary diagnostic tool to detect and define pAMR. However, certain challenges arise for the pathologist. Accurate identification of >10% of intravascular macrophages along with endothelial swelling, which remains a critical component of diagnosing pAMR, is one such challenge. We used double labeling with an endothelial and histiocytic marker to improve diagnostic accuracy. Twenty‐two cardiac transplant endomyocardial biopsies were screened using a CD68/CD31 immunohistochemical (IHC) double stain. To determine whether pAMR diagnosis would change using the double stain, intravascular macrophage staining was compared to using CD68 alone. Twenty‐two cardiac pAMR cases from patients were included. Fifty‐nine percent of cases previously called >10% intravascular macrophage positive by CD68 alone were called <10% positive using the CD68/CD31 double stain. Not using the double stain was associated with a significant overcall. In C4d‐negative cases, using the CD68/CD31 double stain downgraded the diagnosis of pAMR2 to pAMR1 in 32% of cases. It was concluded that more than one third of patients were overdiagnosed with pAMR using CD68 by IHC alone. We demonstrate the value of using a CD68/CD31 double stain to increase accuracy. 相似文献
12.
David F. Pinelli Andrea A. Zachary John J. Friedewald David W. Gjertson Michelle A. Evans Erik N. Chatroop Mary S. Leffell Ashley A. Vo Stanley C. Jordan Robert A. Montgomery Anat R. Tambur 《American journal of transplantation》2019,19(2):381-390
Currently, the ability to predict or monitor the efficacy of HLA antibody–removal therapies is deficient. We previously reported that titration studies are a consistent and accurate means of assessing antibody strength. To test whether titration studies can also predict which patients are better candidates for desensitization, we studied 38 patients from 3 centers (29 receiving plasmapheresis/low‐dose intravenous immunoglobulin [IVIg]; 9 patients receiving high‐dose IVIg). For patients undergoing plasmapheresis/low‐dose IVIg, antibody titer reduction correlated with number of treatment cycles for both class I and II antibodies but only up to approximately 4 cycles. Reduction in titer slowed with additional cycles, suggesting a limit to the efficacy of this approach. Furthermore, initial titer (predesensitization) can guide the selection of candidates for successful antibody‐removal treatment. In our experience, patients with antibodies at an initial titer >1:512 could not be reduced to the goal of a negative lymphocyte crossmatch, corresponding to a 1:16 titer, despite a significant increase in the number of treatment cycles. Change in mean fluorescence intensity (MFI) value did not correlate with success of treatment if initial MFI values were >10 000, likely due to single antigen bead saturation. Overall, we present a potential prognostic tool to predict candidacy and a monitoring tool to assess efficacy of desensitization treatment. 相似文献
13.
Aleksandar Senev Evelyne Lerut Vicky Van Sandt Maarten Coemans Jasper Callemeyn Ben Sprangers Dirk Kuypers Marie‐Paule Emonds Maarten Naesens 《American journal of transplantation》2019,19(11):3100-3113
In this cohort study (N = 924), we investigated the evolution and clinical significance of pretransplant donor‐specific HLA antibodies (preDSA), detected in the single‐antigen beads assay but complement‐dependent cytotoxicity crossmatch‐negative. Donor specificity of the preDSA (N = 107) was determined by high‐resolution genotyping of donor‐recipient pairs. We found that in 52% of the patients with preDSA, preDSA spontaneously resolved within the first 3 months posttransplant. PreDSA that persisted posttransplant had higher pretransplant median fluorescence intensity values and more specificity against DQ. Patients with both resolved and persistent DSA had a high incidence of histological picture of antibody‐mediated rejection (ABMRh; 54% and 59% respectively). Patients with preDSA that persisted posttransplant had worse 10‐year graft survival compared to resolved DSA and preDSA‐negative patients. Compared to cases without preDSA, Cox modeling revealed an increased risk of graft failure only in the patients with persistent DSA, in the presence (hazard ratio [HR] = 8.3) but also in the absence (HR = 4.3) of ABMRh. In contrast, no increased risk of graft failure was seen in patients with resolved DSA. We conclude that persistence of preDSA posttransplant has a negative impact on graft survival, beyond ABMRh. Even in the absence of antibody‐targeting therapy, low median fluorescence intensity DSA and non‐DQ preDSA often disappear early posttransplantation and are not deleterious for graft outcome. 相似文献
14.
Susan S. Wan Steven J. Chadban Narelle Watson Kate Wyburn 《American journal of transplantation》2020,20(5):1351-1364
De novo donor‐specific antibodies (dnDSA) play an important role in antibody‐mediated rejection (ABMR) and graft failure, yet their development in kidney transplant recipients (KTx) of higher immunological risk has not been characterized. We prospectively determined the incidence of dnDSA at 3 and 12 months posttransplant and assessed their associations with outcomes in recipients stratified by low, moderate, and high immunological risk. Adult KTx were screened for DSA pretransplant, months 3 and 12 posttransplant, and when clinically indicated. Outcomes included incidence of dnDSA, death‐censored graft survival (DCGS), and ABMR. Of 371 recipients, 154 (42%) were transplanted across a pretransplant DSA that became undetectable by 12 months posttransplant in 78% of cases. dnDSA were detected in 16% (95% confidence interval [CI]: 12‐20%) by 3 months and 23% (95% CI: 18‐29%) by 12 months posttransplant. Incidence at 12 months was higher in the moderate (30%) and high‐risk groups (29%) compared to the low‐risk group (16%). dnDSA were associated with an increased risk of ABMR (hazard ratio [HR] 2.2; 95% CI: 1.1‐4.4; P = .04) but were not an independent risk factor for DCGS. In conclusion, dnDSA were more frequent in transplant recipients of higher immune risk and associated with an increased risk of ABMR. 相似文献
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Dharmendra Jain Amer Rajab James S. Young Dengping Yin Tibor Nadasdy Anita S. Chong Ronald P. Pelletier 《American journal of transplantation》2020,20(10):2675-2685
Active antibody‐mediated rejection (AMR) is a potentially devastating complication and consistently effective treatment remains elusive. We hypothesized that the reversal of acute AMR requires rapid elimination of antibody‐secreting plasma cells (PC) with a proteasome inhibitor, bortezomib, followed by the sustained inhibition of PC generation with CTLA4‐Ig or belatacept (B/B). We show in mice that B/B therapy selectively depleted mature PC producing donor‐specific antibodies (DSA) and reduced DSA, when administered after primary and secondary DSA responses had been established. A pilot investigation was initiated to treat six consecutive patients with active AMR with B/B. Compassionate use of this regimen was initiated for the first patient who developed early, severe acute AMR that did not respond to steroids, plasmapheresis, and intravenous immunoglobulin after his third kidney transplant. B/B treatment resulted in a rapid reversal of AMR, leading us to treat five additional patients who also resolved their acute AMR episode and had sustained disappearance of circulating DSA for ≤30 months. This study provides a proof‐of‐principle demonstration that mouse models can identify mechanistically rational therapies for the clinic. Follow‐up investigations with a more stringent clinical design are warranted to test whether B/B improves on the standard of care for the treatment of acute AMR. 相似文献
18.
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
19.
Carrie A. Schinstock Andrew J. Bentall Byron H. Smith Lynn D. Cornell Matthew Everly Manish J. Gandhi Mark D. Stegall 《American journal of transplantation》2019,19(6):1671-1683
We aimed to determine the long‐term outcomes of eculizumab‐treated, positive crossmatch (+XM) kidney transplant recipients compared with +XM and age‐matched negative crossmatch (?XM) controls. We performed an observational retrospective study and examined allograft survival, histologic findings, long‐term B‐cell flow cytometric XM (BFXM), and allograft‐loss–associated factors. The mean (SD) posttransplant follow‐up was 6.3 (2.5) years in the eculizumab group; 7.6 (3.5), +XM control group; 7.9 (2.5), ?XM control group. The overall and death‐censored allograft survival rates were similar in +XM groups (P = .73, P = .48) but reduced compared with ?XM control patients (P < .001, P < .001). In the eculizumab‐treated group, 57.9% (11/19) of the allografts had chronic antibody‐mediated rejection, but death‐censored allograft survival was 76.6%, 5 years; 75.4%, 7 years. Baseline IgG3 positivity and BFXM ≥300 were associated with allograft loss. C1q positivity was also associated with allograft loss but did not reach statistical significance. Donor‐specific antibodies appeared to decrease in eculizumab‐treated patients. After excluding patients with posttransplant plasmapheresis, 42.3% (9/21) had negative BFXMs; 31.8% (7/22), completely negative single‐antigen beads 1 year posttransplant. Eculizumab‐treated +XM patients had reduced allograft survival compared with ?XM controls but similar survival to +XM controls. BFXM and complement‐activating donor‐specific antibodies (by IgG3 and C1q testing) may be used for risk stratification in +XM transplantation. 相似文献
20.
Triptolide inhibits donor‐specific antibody production and attenuates mixed antibody‐mediated renal allograft injury 下载免费PDF全文
Daqiang Zhao Siwen Li Tao Liao Yuan Wei Mingyu Liu Fei Han Zihuan Luo Xiaonan Liu Qiquan Sun 《American journal of transplantation》2018,18(5):1083-1095
Donor‐specific antibodies (DSAs) are major mediators of renal allograft injury, and strategies to inhibit DSAs are important in promoting long‐term graft survival. Triptolide exhibits a wide spectrum of antiinflammatory and immunosuppressive activities, and in autoimmune diseases it inhibits autoantibody levels. In this study, we investigated the suppressive role of triptolide in the generation of DSAs in transplant recipients. We found that triptolide treatment of skin allograft recipients in mice significantly suppressed the development of circulating anti‐donor‐specific IgG and effectively alleviated DSA‐mediated renal allograft injury, which led to prolonged allograft survival. In vitro studies revealed that triptolide inhibited the differentiation of B cells into CD138+CD27++ plasma cells; reduced the levels of IgA, IgG, and IgM secreted by plasma cells; and repressed somatic hypermutation and class switch recombination of B cells. Moreover, triptolide‐treated recipients showed reduced numbers of B cells, plasma cells, and memory B cells in spleens and decreased numbers of T, B, natural killer (NK) cells, and macrophages infiltrating grafts. These findings highlight the importance of triptolide in suppressing DSAs and establish triptolide as a novel therapeutic agent for antibody‐mediated allograft rejection. 相似文献