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1.
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
2.
J. M. Gloor J. L. Winters L. D. Cornell L. A. Fix S. R. DeGoey R. M. Knauer F. G. Cosio M. J. Gandhi W. Kremers M. D. Stegall 《American journal of transplantation》2010,10(3):582-589
Renal transplant candidates with donor‐specific alloantibody (DSA) have increased risk of antibody‐mediated allograft injury. The goal of this study was to correlate the risk of antibody‐mediated rejection (AMR), transplant glomerulopathy (TG) and graft survival with the baseline DSA level (prior to initiation of pretransplant conditioning). These analyses include 119 positive crossmatch (+XM) compared to 70 negative crossmatch (?XM) transplants performed between April 2000 and July 2007. Using a combination of cell‐based crossmatch tests, DSA level was stratified into very high +XM, high +XM, low +XM and ?XM groups. In +XM transplants, increasing DSA level was associated with increased risk for AMR (HR = 1.76 [1.51, 2.07], p = 0.0001) but not TG (p = 0.18). We found an increased risk for both early and late allograft loss associated with very high DSA (HR = 7.71 [2.95, 20.1], p = 0.0001). Although lower DSA recipients commonly developed AMR and TG, allograft survival was similar to that of ?XM patients (p = 0.31). We conclude that the baseline DSA level correlates with risk of early and late alloantibody‐mediated allograft injury. With current protocols, very high baseline DSA patients have high rates of AMR and poor long‐term allograft survival highlighting the need for improved therapy for these candidates. 相似文献
3.
G. Bartel M. Wahrmann H. Regele Ž. Kikić G. Fischer W. Druml F. Mühlbacher G. A. Böhmig 《American journal of transplantation》2010,10(9):2033-2042
Various desensitization protocols were shown to enable successful living donor kidney transplantation across a positive complement‐dependent cytotoxicity crossmatch (CDCXM). Positive crossmatch transplantation, however, is less well established for deceased donor transplantation. We report a cohort of 68 deceased donor renal allograft recipients who, on the basis of broad sensitization (lymphocytotoxic panel reactivity ≥40%), were subjected to a protocol of peritransplant immunoadsorption (IA). Treatment consisted of a single session of immediate pretransplant IA (protein A) followed by posttransplant IA and antilymphocyte antibody therapy. Twenty‐one patients had a positive CDCXM, which could be rendered negative by pretransplant apheresis. Solid phase HLA antibody detection revealed preformed donor‐specific antibodies (DSA) in all 21 CDCXM‐positive and in 30 CDCXM‐negative recipients. At 5 years, overall graft survival, death‐censored graft survival and patient survival were 63%, 76% and 87%, respectively, without any differences between CDCXM‐positive, CDCXM‐negative/DSA‐positive and CDCXM‐negative/DSA‐negative recipients. Furthermore, groups did not differ regarding rates of antibody‐mediated rejection (24% vs. 30% vs. 24%, p = 0.84), cellular rejection (14% vs. 23% vs. 18%, p = 0.7) or allograft function (median 5‐year serum creatinine: 1.3 vs. 1.8 vs. 1.7 mg/dL, p = 0.62). Our results suggest that peritransplant IA is an effective strategy for rapid desensitization in deceased donor transplantation. 相似文献
4.
Hideki Ishida Miyuki Furusawa Tomokazu Shimizu Taiji Nozaki Kazunari Tanabe 《Transplant international》2014,27(4):371-382
We investigated the relationship between preoperative anti‐HLA antibodies (donor‐specific antibody, DSA) and the graft survival rate in recipients who had or had not received rituximab (Rit) treatment. The subjects were categorized into four groups as follows: DSA+Rit?, n = 39; DSA?Rit?, n = 121; DSA+Rit+, n = 74; and DSA?Rit+, n = 47. We examined the influence of preoperative DSA on the incidence of graft rejection and the survival rate of recipients who had or who had not received rituximab before transplantation. The 6‐month acute rejection rates based on graft biopsies were 39%, 19%, 15%, and 0% for the DSA+Rit?, DSA?Rit?, DSA+Rit+, and DSA?Rit+ groups. The rates of chronic antibody‐mediated rejection after more than 6 months were 50%, 22%, 18%, and 0%. The 5‐year graft survival rate was significantly lower in the DSA+Rit? group (84%) than in the other groups (95% for DSA?Rit?, 98% for DSA+Rit+, and 91% for DSA?Rit+). The rate of the appearance of de novo anti‐HLA antibodies was higher in the groups that did not receive rituximab treatment. The rate of graft loss associated with chronic antibody‐mediated rejection was also higher in the DSA+Rit? group than in the other groups (P = 0.01). The presence of DSA and the administration of rituximab had strong impacts on not only short‐term graft rejection, but also long‐term graft rejection and its association with the graft survival time. 相似文献
5.
Jordan SC Reinsmoen N Lai CH Cao K Kahwaji J Peng A Villicana R Vo A 《Transplantation proceedings》2012,44(1):60-61
For broadly human leukocyte antigen-sensitized patients (HS; calculated panel-reactive antibody >80%), options for deceased donor (DD) transplantation are extremely limited. Data from United Network for Organ Sharing (2000-2009) indicate that <10% of HS patients are transplanted each year. Immune modulation of HS patients using intravenous immunoglobulin (IVIG) and rituximab has shown promise in reducing donor-specific antibody (DSA) titers and improving the chances for successful transplantation for patients awaiting DD transplants. Critical to the success of desensitization with IVIG + rituximab is a coherent antibody-testing strategy aimed at detection of DSA reductions and identification of crossmatch parameters that are associated with a low likelihood of antibody-mediated rejection posttransplant. Here, we discuss data that examine the efficacy of IVIG + rituximab in reducing DSA levels and improving chances for a successful DD transplantation. Patient and graft survival data are also presented as is an analysis of the safety of IVIG + rituximab in sensitized patients. 相似文献
6.
J. G. O'Leary H. M. Gebel R. Ruiz R. A. Bray J. D. Marr X. J. Zhou S. M. Shiller B. M. Susskind A. D. Kirk G. B. Klintmalm 《American journal of transplantation》2013,13(4):954-960
Hyperacute kidney rejection is unusual in crossmatch positive recipients of simultaneous liver–kidney transplants (SLKT). However, recent data suggest that these patients remain at risk for antibody‐mediated kidney rejection. To further investigate the risk associated with donor‐specific alloantibodies (DSA) in SLKT, we studied 86 consecutive SLKT patients with an available pre‐SLKT serum sample. Serum samples were analyzed in a blinded fashion for HLA DSA using single antigen beads (median florescence intensity ≥ 2,000 = positive). Post‐SLKT samples were analyzed when available (76%). Thirty patients had preformed DSA, and nine developed de novo DSA. Preformed class I DSA did not change the risk of rejection, patient or allograft survival. In contrast, preformed class II DSA was associated with a markedly increased risk of renal antibody mediated rejection (AMR) (p = 0.006), liver allograft rejection (p = 0.002), patient death (p = 0.02), liver allograft loss (p = 0.02) and renal allograft loss (p = 0.045). Multivariable modeling showed class II DSA (preformed or de novo) to be an independent predictor of patient death (HR = 2.2; p = 0.043) and liver allograft loss (HR = 2.2; p = 0.044). These data warrant reconsideration of the approach to DSA in SLKT. 相似文献
7.
D. K. Perry J. M. Burns H. S. Pollinger B. P. Amiot J. M. Gloor G. J. Gores M. D. Stegall 《American journal of transplantation》2009,9(1):201-209
Antibody production by normal plasma cells (PCs) against human leukocyte antigens (HLA) can be a major barrier to successful transplantation. We tested four reagents with possible activity against PCs (rituximab, polyclonal rabbit antithymocyte globulin (rATG), intravenous immunoglobulin (IVIG) and the proteasome inhibitor, bortezomib) to determine their ability to cause apoptosis of human bone marrow-derived PCs and subsequently block IgG secretion in vitro . IVIG, rituximab and rATG all failed to cause apoptosis of PCs and neither rituximab nor rATG blocked antibody production. In contrast, bortezomib treatment led to PC apoptosis and thereby blocked anti-HLA and antitetanus IgG secretion in vitro . Two patients treated with bortezomib for humoral rejection after allogeneic kidney transplantation demonstrated a transient decrease in bone marrow PCs in vivo and persistent alterations in alloantibody specificities. Total IgG levels were unchanged. We conclude that proteasome activity is important for PC longevity and its inhibition may lead to new techniques of controlling antibody production in vivo . 相似文献
8.
Matignon M Tagnaouti M Audard V Dahan K Lang P Grimbert P 《Transplantation proceedings》2007,39(8):2565-2567
There is no optimal desensitization protocol for cadaveric renal transplant recipients who display high levels of donor-specific alloantibodies as defined by a positive T- or B-cell cytotoxic crossmatch. We used anti-CD20 monoclonal antibodies (Rituximab) to try to prevent antibody-mediated rejection in three crossmatch-positive renal transplants recipients (standard and sensitized techniques). The three patients received a first, second, or third cadaveric donor renal transplant. Patient one had an historical positive T- and B-cell cytotoxicity crossmatch: negative T- and B-cell cytotoxicity crossmatch at the day of transplantation. The panel reactive antibody (PRA) level was 100%. Patients 2 and 3 showed positive B-cell cytotoxicity crossmatches: historical and on the day of transplantation; PRA levels were 50% and 71%, respectively. All recipients were treated pretransplant with rituximab (375 mg/m(2)) and 4 days of intravenous immunoglobulin (0.5 g/kg body weight) per day posttransplant plus 5 days of thymoglobulin. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and prednisone. Antibody-mediated rejection occurred in all patients at day 6, day 10, or 8 months after renal transplantation. For patient 1, the rejection was not reversible and the graft was lost at day 15. Patient 2 had poor renal function with an MDRD estimate of glomerular filtration rate at 36 mL/min/1.73 m(2) at 18 months posttransplantation, and the graft of patient 3 was lost at 9 months posttransplantation due to resistant antibody-mediated rejection with thrombotic microangiopathy. In these three cases of crossmatch-positive patients, rituximab failed to prevent antibody-mediated rejection. Others studies will be needed to determine the place of rituximab in these patients. 相似文献
9.
Pediatric heart transplantation across a positive crossmatch: First year results from the CTOTC‐04 multi‐institutional study
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S. Webber A. Zeevi K. Mason L. Addonizio E. Blume A. Dipchand R. Shaddy B. Feingold C. Canter D. Hsu W. Mahle B. Armstrong Y. Morrison D. Ikle H. Diop J. Odim the CTOTC‐ Investigators 《American journal of transplantation》2018,18(9):2148-2162
Sensitization is common in pediatric heart transplant candidates and waitlist mortality is high. Transplantation across a positive crossmatch may reduce wait time, but is considered high risk. We prospectively recruited consecutive candidates at eight North American centers. At transplantation, subjects were categorized as nonsensitized or sensitized (presence of ≥1 HLA antibody with MFI ≥1000 using single antigen beads). Sensitized subjects were further classified as complement‐dependent cytotoxicity crossmatch (CDC‐crossmatch) positive or negative and as donor‐specific antibodies (DSA) positive or negative. Immunosuppression was standardized. CDC‐crossmatch–positive subjects also received perioperative antibody removal, maintenance corticosteroids, and intravenous immunoglobulin. The primary endpoint was the 1 year incidence rate of a composite of death, retransplantation, or rejection with hemodynamic compromise. 317 subjects were screened, 290 enrolled and 240 transplanted (51 with pretransplant DSA, 11 with positive CDC‐crossmatch). The incidence rates of the primary endpoint did not differ statistically between groups; nonsensitized 6.7% (CI: 2.7%, 13.3%), sensitized crossmatch positive 18.2% (CI: 2.3%, 51.8%), sensitized crossmatch negative 10.7% (CI: 5.7%, 18.0%), P = .2354. The primary endpoint also did not differ by DSA status. Freedom from antibody‐mediated and cellular rejection was lower in the crossmatch positive group and/or in the presence of DSA. Follow‐up will determine if acceptable outcomes can be achieved long‐term. 相似文献
10.
Outcome of the risk‐stratified desensitization protocol in donor‐specific antibody‐positive living kidney transplant recipients: a retrospective study
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Daigo Okada Masayoshi Okumi Yoichi Kakuta Kohei Unagami Junpei Iizuka Toshio Takagi Hideki Ishida Kazunari Tanabe 《Transplant international》2018,31(9):1008-1017
Acceptable outcomes of donor‐specific antibody (DSA)‐positive living kidney transplantation (LKT) have recently been reported. However, LKT in crossmatch (XM)‐positive patients remains at high‐risk and requires an optimal desensitization protocol. We report our intermediate‐term outcomes of XM‐positive LKT vs. XM‐negative LKT in patients who underwent LKT between January 2012 and June 2015 in our institution. The rate of acute antibody‐mediated rejection (ABMR) within 90 days postoperation, graft function, and patient, and graft survival rates at 4 years were investigated. Patients were divided into three groups: XM?DSA? (n = 229), XM?DSA+ (n = 36), and XM + DSA+ (n = 15). The XM + DSA+ group patients underwent desensitization with high‐dose intravenous immunoglobulin, plasmapheresis, and rituximab. The rates of ABMR within 90 days in the XM?DSA?, XM?DSA+, and XM + DSA+ groups were 1.3%, 9.4%, and 60.0%, respectively (P < 0.001). There were no significant differences in the graft function throughout the observational period, the 4‐year patient or graft survival rates among three groups. This study showed that intermediate‐term outcomes of XM‐positive LKT were comparable to XM‐negative LKT. However, our current desensitization protocol cannot avert ABMR within 90 days, and XM positivity is still a significant risk factor for ABMR. Further refinement of the current desensitization regimen is required. 相似文献
11.
A New Diagnostic Algorithm for Antibody‐Mediated Microcirculation Inflammation in Kidney Transplants
B. Sis G. S. Jhangri J. Riopel J. Chang D. G. de Freitas L. Hidalgo M. Mengel A. Matas P. F. Halloran 《American journal of transplantation》2012,12(5):1168-1179
We studied the significance of microcirculation inflammation in kidney transplants, including 329 indication biopsies from 251 renal allograft recipients, who were mostly nonpresensitized (crossmatch negative). Glomerulitis (g) and peritubular capillaritis (ptc) were often associated with antibody‐mediated rejection (65% and 75%, respectively), but were also found in other diseases in the absence of donor‐specific antibody (DSA): T‐cell‐mediated rejection (ptc, g), glomerulonephritis (g) and acute tubular necrosis (ptc). To develop rules for reducing the nonspecificity of microcirculation inflammation and defining the best grading thresholds associated with DSA, we built and validated a decision tree to predict DSA. The decision tree revealed that g + ptc sum (addition of g‐score plus ptc‐score) was the best predictor of DSA, followed by time posttransplant, then C4d, which had a small role. Late biopsies with g + ptc > 0 showed higher frequency of DSA compared to early biopsies with g + ptc > 0 (79% vs. 27%). Microcirculation inflammation in early biopsies was often false positive (antibody‐independent). The decision tree predicted DSA with higher sensitivity and accuracy than C4d staining. Microcirculation inflammation sum score predicted graft failure independently of time, C4d and transplant glomerulopathy. Thus any degree of microcirculation inflammation in late kidney transplant biopsies strongly indicates presence of DSA and predicts progression to graft failure. 相似文献
12.
Daclizumab Versus Rabbit Antithymocyte Globulin in High‐Risk Renal Transplants: Five‐Year Follow‐up of a Randomized Study
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D. Durand G. Mourad P. Lang M. Kessler B. Charpentier G. Touchard F. Berthoux P. Merville N. Ouali J.‐P. Squifflet F. Bayle K. M. Wissing D. Abramowicz 《American journal of transplantation》2015,15(7):1923-1932
We previously reported a randomized controlled trial in which 227 de novo deceased‐donor kidney transplant recipients were randomized to rabbit antithymocyte (rATG, Thymoglobulin) or daclizumab if they were considered to be at high immunological risk, defined as high panel reactive antibodies (PRA), loss of a first kidney graft through rejection within 2 years of transplantation, or third or fourth transplantation. Patients treated with rATG had lower incidences of biopsy‐proven acute rejection (BPAR) and steroid‐resistant rejection at 1 year. Patients were followed to 5 years posttransplant in an observational study; findings are described here. Treatment with rATG was associated with a lower rate of BPAR at 5 years (14.2% vs. 26.0% with daclizumab; p = 0.035). Only one rATG‐treated patient (0.9%) and one daclizumab‐treated patient (1.0%) developed BPAR after 1 year. Five‐year graft and patient survival rates, and renal function, were similar between the two groups. Overall graft survival at 5 years was significantly higher in patients without BPAR (81.0% vs. 54.8%; p < 0.001). In conclusion, rATG is superior to daclizumab for the prevention of BPAR among high‐immunological‐risk renal transplant recipients. Overall graft survival at 5 years was approximately 70% with either induction therapy, which compares favorably to low‐risk cohorts. 相似文献
13.
Lunz J Ruppert KM Cajaiba MM Isse K Bentlejewski CA Minervini M Nalesnik MA Randhawa P Rubin E Sasatomi E de Vera ME Fontes P Humar A Zeevi A Demetris AJ 《American journal of transplantation》2012,12(1):171-182
C4d-assisted recognition of antibody-mediated rejection (AMR) in formalin-fixed paraffin-embedded tissues (FFPE) from donor-specific antibody-positive (DSA+) renal allograft recipients prompted study of DSA+ liver allograft recipients as measured by lymphocytotoxic crossmatch (XM) and/or Luminex. XM results did not influence patient or allograft survival, or cellular rejection rates, but XM+ recipients received significantly more prophylactic steroids. Endothelial C4d staining strongly correlates with XM+ (<3 weeks posttransplantation) and DSA+ status and cellular rejection, but not with worse Banff grading or treatment response. Diffuse C4d staining, XM+, DSA+ and ABO- incompatibility status, histopathology and clinical-serologic profile helped establish an isolated AMR diagnosis in 5 of 100 (5%) XM+ and one ABO-incompatible, recipients. C4d staining later after transplantation was associated with rejection and nonrejection-related causes of allograft dysfunction in DSA- and DSA+ recipients, some of whom had good outcomes without additional therapy. Liver allograft FFPE C4d staining: (a) can help classify liver allograft dysfunction; (b) substantiates antibody contribution to rejection; (c) probably represents nonalloantibody insults and/or complete absorption in DSA- recipients and (d) alone, is an imperfect AMR marker needing correlation with routine histopathology, clinical and serologic profiles. Further study in late biopsies and other tissue markers of liver AMR with simultaneous DSA measurements are needed. 相似文献
14.
T. B. Dunn H. Noreen K. Gillingham D. Maurer O. G. Ozturk T. L. Pruett R. A. Bray H. M. Gebel A. J. Matas 《American journal of transplantation》2011,11(10):2132-2143
Single‐antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor‐specific antibody (DSA). We grouped 587 kidney transplants using clinical history and single‐antigen bead (SAB) testing of day of transplant serum as (1) unsensitized; PRA = 0 (n = 178), (2) third‐party sensitized; no DSA (n = 363) or (3) donor sensitized; with DSA (n = 46), and studied rejection rates, death‐censored graft survival (DCGS) and risk factors for rejection. Antibody‐mediated rejection (AMR) rates were increased with DSA (p < 0.0001), but not with panel reactive antibody (PRA) in the absence of DSA. Cell‐mediated rejection (CMR) rates were increased with DSA (p < 0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p = 0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization. 相似文献
15.
Sureshkumar KK Hussain SM Marcus RJ Ko TY Khan AS Tom K Vivas CA Parris G Jasnosz KM Thai NL 《Clinical nephrology》2012,77(3):246-253
Antibody-mediated rejection (AMR) following renal transplantation is less responsive to conventional anti-rejection therapies. Plasmapheresis (PP), intravenous immunoglobulin (IVIg), rabbit antithymocyte globulin (rATG) and rituximab deplete immature B-cells but not mature plasma cells. The proteasome inhibitor bortezomib has activity against mature plasma cell, the source of damaging donor-specific antibody (DSA).We present the successful use of bortezomib in 2 patients who developed AMR following kidney transplantation. The first patient was a 54-year-old white female who received living-unrelated kidney transplantation from her husband. She developed severe AMR early after transplantation with rising DSA titers consistent with an anamnestic immune response by memory cells to the donor antigens. Renal function deteriorated despite treatment with pulse methylprednisolone (MP), PP and IVIg. After initiation of therapy with bortezomib, DSA titers became negative and serum creatinine returned to baseline with histological resolution of AMR. The second patient was a 19-year-old white male who received deceased donor kidney transplantation and developed AMR within 2 weeks, refractory to therapy with pulse MP, PP and IVIg with rising DSA. Bortezomib use resulted in disappearance of DSA and renal function improvement. Both patients tolerated the treatment well with stable renal function at last follow-up. The novel mechanisms of action and preliminary results with bortezomib are encouraging, but require larger studies and longer follow-up. 相似文献
16.
M. J. Everly J. J. Everly L. J. Arend P. Brailey B. Susskind A. Govil A. Rike P. Roy-Chaudhury G. Mogilishetty R. R. Alloway A. Tevar E. S. Woodle 《American journal of transplantation》2009,9(5):1063-1071
The effect of de novo DSA detected at the time of acute cellular rejection (ACR) and the response of DSA levels to rejection therapy on renal allograft survival were analyzed. Kidney transplant patients with acute rejection underwent DSA testing at rejection diagnosis with DSA levels quantified using Luminex single-antigen beads. Fifty-two patients experienced acute rejection with 16 (31%) testing positive for de novo DSA. Median follow-up was 27.0 ± 17.4 months postacute rejection. Univariate analysis of factors influencing allograft survival demonstrated significance for African American race, DGF, cytotoxic PRA >20% (current) and/or >50% (peak), de novo DSA, C4d and repeat transplantation. Multivariate analysis showed only de novo DSA (6.6-fold increased allograft loss risk, p = 0.017) to be significant. Four-year allograft survival was higher with ACR (without DSA) (100%) than mixed acute rejection (ACR with DSA/C4d) (65%) or antibody-mediated rejection (35%) (p < 0.001). Patients with >50% reduction in DSA within 14 days experienced higher allograft survival (p = 0.039). De novo DSAs detected at rejection are associated with reduced allograft survival, but prompt DSA reduction was associated with improved allograft survival. DSA should be considered a potential new end point for rejection therapy. 相似文献
17.
H. S. Eng G. Bennett E. Tsiopelas M. Lake I. Humphreys S. H. Chang P. T. H. Coates G. R. Russ 《American journal of transplantation》2008,8(11):2335-2342
The significance of B‐cell crossmatching in kidney transplantation is controversial. Recipients (n = 471) transplanted in a single centre from 1987 to 2005 with complete T‐ and B‐cell crossmatch records were studied. Sera from 83 patients transplanted across a positive B‐cell crossmatch, with concomitant negative T‐cell crossmatch (T–B+) on either current and/or peak sera were studied using Luminex® to determine presence of donor‐specific antibodies (DSA). Clinical outcomes of T–B+ patients were compared with 386 T–B? patients. T–B+ predicted vascular (p = 0.01), but not cellular (p = 0.82) or glomerular (p = 0.14) rejection. IgG HLA DSA were found in 33% (n = 27) of the T–B+ patients and were associated with higher risk of any (p = 0.047), vascular (p = 0.01) or glomerular (p < 0.001) rejection at 6 months. Of 27 patients with DSA, 18/21 (86%) were the complement‐fixing IgG1 and/or IgG3 subclass antibodies. DSA imposed a statistically significant higher risk of graft loss 5 years posttransplant (1.8 [1.0–3.3], p = 0.045). This study showed that only one‐third of positive B‐cell crossmatch (BXM) was caused by DSA and was associated with late graft loss. Thus, using BXM to preclude kidney transplantation may potentially disadvantage >60% of patients in whom BXM is not indicative of the presence of DSA. 相似文献
18.
The antibody crossmatch in liver transplantation 总被引:3,自引:0,他引:3
R D Gordon J J Fung B Markus I Fox S Iwatsuki C O Esquivel A Tzakis S Todo T E Starzl 《Surgery》1986,100(4):705-715
Six hundred sixty-seven first, second, and third orthotopic liver allografts in 520 patients were reviewed to determine the effect of recipient panel-reactive antibody (PRA) and donor-recipient antibody crossmatch on 2-year patient and liver allograft survival rates. Neither a high panel-reactive antibody nor a positive crossmatch for donor-specific preformed antibody was associated with decreased patient or liver allograft survival for primary grafts or retransplants. Two patients have been given kidney transplants immediately after a liver allograft from a donor with whom each patient had an initial strongly positive donor-specific antibody crossmatch. The liver apparently removed or neutralized circulating anti-donor antibody, since the renal allografts functioned promptly and did not experience hyperacute rejection. 相似文献
19.
This case describes a 34 year old female who underwent an HLA identical living donor kidney transplant with a positive flow cytometric crossmatch (FCXM), but without any donor specific antibody (DSA). Tests to detect non-HLA antibody and autoantibody were negative. Allograft functioned well without rejection. She later received a pancreas allograft, again with a weakly positive FCXM, without DSA. After good initial graft function, she developed hyperglycemia six weeks posttransplant. Cross-sectional imaging demonstrated non-enhancing pancreas allograft with new vein thrombosis. She underwent transplant pancreatectomy, the explant pathology demonstrated changes consistent with severe acute antibody mediated rejection (AMR) causing thrombosis of the pancreas allograft. She had also developed several de-novo class-I DSAs at this time. Despite extensive testing, we could not identify a causative antibody for the initial positive FCXMs or its role in the eventual rejection of the pancreas allograft. 相似文献
20.
Gaetano Lucisano Srivathsan Thiruvengadam Sevda Hassan Alexander Gueret‐Wardle Paul Brookes Eva Santos‐Nunez Michelle Willicombe 《American journal of transplantation》2020,20(2):441-450
Whether reexposure to mismatched HLA antigens (RMM) in the setting of a negative crossmatch is associated with increased immunological risk remains an area of uncertainty. This is due to evidence derived predominantly from registry data, which lacks comprehensive information on alloantibody and rejection. In this study, we analyze the impact of low‐level preformed donor‐specific antibodies (DSA) against an RMM on transplant outcomes. From 1988 consecutive renal transplant recipients, we analyzed 179 patients undergoing retransplantation, of whom 55 had a RMM. All patients were crossmatch negative and preformed DSA were detected by single antigen beads alone. Multivariate analysis revealed that patients with preformed DSA against an RMM were independently at risk of antibody‐mediated rejection (HR 8.70 [3.42‐22.10], P < .0001) and death‐censored allograft loss (HR 3.08 [1.17‐8.14], P = .023). In addition, prior transplant nephrectomy (HR 2.04 [1.00‐4.17], P = .0495) was also associated with allograft failure, whereas receiving a retransplant that was matched at HLA class II was associated with a favorable outcome (HR 0.37 [0.14‐0.99], P = .047). In the absence of preformed DSA, an RMM was not associated with de novo DSA development, rejection, or allograft loss. In conclusion, an RMM portends increased immunological risk only in the presence of a preformed DSA in patients undergoing retransplantation. 相似文献