Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the produc...Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.展开更多
Allo-antibodies, particularly when donor specific, are one of the most important factors that cause both early and late graft dysfunction. The authors review the current state of the art concerning this important issu...Allo-antibodies, particularly when donor specific, are one of the most important factors that cause both early and late graft dysfunction. The authors review the current state of the art concerning this important issue in renal transplantation. Many antibodies have been recognized as mediators of renal injury. In particular donorspecific-Human Leukocyte Antigens antibodies appear to play a major role. New techniques, such as solid phase techniques and Luminex, have revealed these antibodies from patient sera. Other new techniques have uncovered alloantibodies and signs of complement activation in renal biopsy specimens. It has been acknowledged that the old concept of chronic renal injury caused by calcineurine inhibitors toxicity should be replaced in many cases by alloantibodies acting against the graft. In addition, the number of patients on waiting lists with preformed anti-human leukocyte antigens(HLA) antibodies is increasing, primarily from patients with a history of renal transplant failure already been sensitized. We should distinguish early and late acute antibody-mediated rejection from chronic antibody-mediated rejection. The latter often manifets late during the course of the posttransplant period and may be difficult to recognize if specific techniques are not applied. Different therapeutic strategies are used to control antibody-induced damage.These strategies may be applied prior to transplantation or, in the case of acute antibody-mediated rejection, after transplantation. Many new drugs are appearing at the horizon; however, these drugs are far from the clinic because they are in phase Ⅰ-Ⅱ of clinical trials. Thus the pipeline for the near future appears almost empty.展开更多
AIM To analyze the clinical impact of preformed antiH LA-Cw vs antiH LA-A and/or-B donor-specific antibodies(DSA) in kidney transplantation.METHODS Retrospective study, comparing 12 patients transplanted with DSA excl...AIM To analyze the clinical impact of preformed antiH LA-Cw vs antiH LA-A and/or-B donor-specific antibodies(DSA) in kidney transplantation.METHODS Retrospective study, comparing 12 patients transplanted with DSA exclusively antiH LA-Cw with 23 patients with preformed DSA antiH LA-A and/or B.RESULTS One year after transplantation there were no differencesin terms of acute rejection between the two groups(3 and 6 cases, respectively in the DSA-Cw and the DSA-A-B groups; P = 1). At one year, eG FR was not significantly different between groups(median 59 mL /min in DSA-Cw group, compared to median 51 mL /min in DSA-A-B group, P = 0.192). Moreover, kidney graft survival was similar between groups at 5-years(100% in DSA-Cw group vs 91% in DSA-A-B group, P = 0.528). The sole independent predictor of antibody mediated rejection(AMR) incidence was DSA strength(HR = 1.07 per 1000 increase in MFI, P = 0.034). AMR was associated with shortened graft survival at 5-years, with 75% and 100% grafts surviving in patients with or without AMR, respectively(Log-rank P = 0.005).CONCLUSION Our data indicate that DSA-Cw are associated with an identical risk of AMR and impact on graft function in comparison with "classical" class I DSA.展开更多
The γc cytokines play an important role in proliferation and survival of T cells. Blocking the γc signals can cause the activated donor-reactive T cells losing the ability to proliferate, and getting into apoptosis ...The γc cytokines play an important role in proliferation and survival of T cells. Blocking the γc signals can cause the activated donor-reactive T cells losing the ability to proliferate, and getting into apoptosis pathway, which contributes to induction of the peripheral tolerance. In this study, we induced the transplant tolerance through blocking the γc in combination with donor-specific transfusion (DST) in the cardiac transplantation. Following DST, on the day 2, 4 and 6, C57BL/6 recipients received anti-γc monoclonal antibodies (mAbs) injection, and those in control group were not given anti-γc mAbs. On the day 7, Balb/c cardiac allografts were transplanted. All recipients in experimental group accepted cardiac allografts over 30 days, and two of them accepted allografts without rejection until sacrifice on the 120 day. Animals only receiving DST rejected grafts within 5 days, and the mice receiving cardiac transplantation alone rejected grafts within 9 days. Our study showed that blockade of γc signaling combined with DST significantly prolonged allograft survival, which was probably associated with inhibition of antigen-specific T-cell proliferation and induction of apoptosis.展开更多
AIM To investigate the incidence, risk factors and clinical outcomes of acute antibody-mediated rejection(ABMR) after intestinal transplantation(ITx).METHODS A retrospective single-center analysis was performed to ide...AIM To investigate the incidence, risk factors and clinical outcomes of acute antibody-mediated rejection(ABMR) after intestinal transplantation(ITx).METHODS A retrospective single-center analysis was performed to identify cases of acute ABMR after ITx, based on the presence of donor-specific antibody(DSA), acute tissue damage, C4 d deposition, and allograft dysfunction.RESULTS Acute ABMR was identified in 18(10.3%) out of 175 intestinal allografts with an average occurrence of 10 d(range, 4-162) after ITx. All acute ABMR cases were presensitized to donor human leukocyte antigens class Ⅰand/or Ⅱ antigens with a detectable DSA. A positive cross-match was seen in 14(77.8%) cases and twelve of 18 patients(66.7%) produced newly-formed DSA following ITx. Histological characteristics of acute ABMR include endothelial C4 d deposits, interstitial hemorrhage, and severe congestion with focal fibrin thrombin in the lamina propria capillaries. Multivariate analysis identified a liver-free graft and high level of panel reactive antibodyas a significant independent risk factor. Despite initial improvement after therapy, eleven recipients(61.1%) lost transplant secondary to rejection. Of those, 9(50%) underwent graft removal and 4(22.2%) received second transplantation following acute ABMR. At an average follow-up of 32.3 mo(range, 13.3-76.4), 8(44.4%) recipients died.CONCLUSION Our results indicate that acute ABMR is an important cause of intestine graft dysfunction, particularly in a liver-exclusive graft and survivors are at an increased risk of developing refractory acute rejection and chronic rejection. More effective strategies to prevent and manage acute ABMR are needed to improve outcomes.展开更多
BACKGROUND The liver has traditionally been regarded as resistant to antibody-mediated rejection(AMR).AMR in liver transplants is a field in its infancy compared to kidney and lung transplants.In our case we present a...BACKGROUND The liver has traditionally been regarded as resistant to antibody-mediated rejection(AMR).AMR in liver transplants is a field in its infancy compared to kidney and lung transplants.In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure(ALF)with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies(DSA).This case highlights the need for further investigations and heightened awareness for timely diagnosis.CASE SUMMARY A 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor.The recipient MELD at the time of transplant was 28.The flow cytometric crossmatches were noted to be positive for T and B lymphocytes.The patient had an uneventful recovery postoperatively.Starting on postoperative day 5 the patient developed fevers,elevated liver function tests,distributive shock,renal failure,and hepatic encephalopathy.She went into ALF with evidence of antibody mediated rejection with portal inflammation,bile duct injury,endothelitis,and extensive centrizonal necrosis,and C4d staining on allograft biopsy and elevated DSA.Despite various interventions including plasmapheresis and immunomodulating therapy,she continued to deteriorate.She was relisted and successfully underwent liver retransplantation.CONCLUSION This very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.展开更多
AIM To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab in chronic-active antibody-mediated rejection(c AMR) settings.METHODS We compared 21 kidney transplant ...AIM To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab in chronic-active antibody-mediated rejection(c AMR) settings.METHODS We compared 21 kidney transplant recipients(KTRs) with a diagnosis of c AMR in a retrospective casecontrol analysis: nine KTRs treated with plasmapheresis, intravenous immunoglobulins and rituximab(PE-IVIGRTX group) vs 12 patients(control group) not treated with antibody-targeted therapies. We examined kidney survival and functional outcomes 24 mo after diagnosis. Histological features and donor-specific antibody(DSA) characteristics(MFI and C1 q-fixing ability) were also investigated.RESULTS No difference in graft survival between the two groups was noted: three out of nine patients in the PE-IVIG-RTX group(33.3%) and 4/12 in the control group(33.3%) experienced loss of allograft function at a median time after diagnosis of 14 mo(min 12-max 18) and 15 mo(min 7-max 22), respectively. Kidney functional tests and proteinuria 24 mo after cA MR diagnosis were also similar in both groups. Only microvascular inflammation(glomerulitis + peritubular capillaritis score) was significantly reduced after PE-IVIG-RTX in seven out of eight patients(87.5%) in the PE-IVIG-RTX group(median score 3 in pre-treatment biopsy vs 1.5 in post-treatment biopsy; P = 0.047), without any impact on kidney survival and/or DSA characteristics. No functional or histological parameter at diagnosis was predictive of clinical outcome.CONCLUSION Our data showed no difference in the two year posttreatment outcome of kidney grafts treated with PE-IVIGRTX for c AMR diagnosis, however there were notable improvements in microvascular inflammation in posttherapy protocol biopsies. Further studies, especially involving innovative therapeutic approaches, are required to improve the management and long-term results of this severe condition.展开更多
Antibody-mediated rejection(ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation(ITx). Compelling evidence indicates that donor-specific antibodies can mediate and pr...Antibody-mediated rejection(ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation(ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibodymediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation.展开更多
AIM To investigate the role of glutathione S-transferase T1 donor-specific T lymphocytes in plasma cell-rich rejection of liver allografts.METHODS The study group included 22 liver transplant patients. Among them, 18 ...AIM To investigate the role of glutathione S-transferase T1 donor-specific T lymphocytes in plasma cell-rich rejection of liver allografts.METHODS The study group included 22 liver transplant patients. Among them, 18 patients were mismatched for the glutathione S-transferase T1(GSTT1) alleles(don+/rec-), and 4 were matched(don+/rec+). Seven of the mismatched patients produced anti-GSTT1 antibodies and developed plasma cell-rich rejection(former de novo immune hepatitis). For the detection of specific Tlymphocytes, peripheral blood mononuclear cells were collected and stored in liquid nitrogen. The memory T cell response was studied by adding to the cell cultures to a mix of 39 custom-made, 15-mer overlapping peptides, which covered the entire GSTT1 amino acid sequence. The specific cellular response to peptides was analyzed by flow cytometry using the markers CD8, CD4, IL-4 and IFNγ.RESULTS Activation of CD8^+ T cells with different peptides was observed exclusively in the group of patients with plasma-cell rich rejection(3 out of 7), with production of IL-4 and/or IFNγ at a rate of 1%-4.92% depending on the peptides. The CD4^+ response was most common and not exclusive for patients with the disease, where 5 out of 7 showed percentages of activated cells from 1.24% to 31.34%. Additionally, two patients without the disease but with the mismatch had cells that became stimulated with some peptides(1.45%-5.18%). Highly unexpected was the finding of a double positive CD4^+CD8^(low) T cell population that showed the highest degree of activation with some of the peptides in 7 patients with the mismatch, in 4 patients with plasma cell-rich rejection and in 3 patients without the disease. Unfortunately, CD4^+CD8^(low) cells represent 1% of the total number of lymphocytes, and stimulation could not be analyzed in 9 patients due to the low number of gated cells. Cells from the 4 patients included as controls did not show activation with any of the peptides. CONCLUSION Patients with GSTT1 mismatch can develop a specific T-cell response, but the potential role of this response in the pathogenesis of plasma cell-rich rejection is unknown.展开更多
目的:临床上预存供者特异性抗体(donor specific antibody,DSA)患者术后易发生抗体介导的排斥反应(antibody-mediated rejection,AMR),术后发生并发症和移植失败的风险相对较高。本研究旨在探讨DSA阳性肾移植临床治疗效果并分析术前预...目的:临床上预存供者特异性抗体(donor specific antibody,DSA)患者术后易发生抗体介导的排斥反应(antibody-mediated rejection,AMR),术后发生并发症和移植失败的风险相对较高。本研究旨在探讨DSA阳性肾移植临床治疗效果并分析术前预处理在DSA阳性肾移植中的作用与安全性,为临床DSA阳性肾移植提供单中心治疗经验。方法:回顾性分析郑州大学第一附属医院肾移植科的15例DSA阳性肾移植患者的临床资料,8例为公民逝世后器官捐献来源(organ donation after citizen’s death,DCD)肾移植受者,其中3例在术前未作脱敏治疗(DCD未处理组,n=3),5例受者在术前使用利妥昔单抗作脱敏治疗(DCD预处理组,n=5);其余7例为亲属活体供者(living related donors,LRD)肾移植受者,术前接受利妥昔单抗和血浆置换脱敏治疗(LRD预处理组,n=7)。收集受者肾功能,DSA水平变化,并发症发生情况,术后1年、3年及5年受者和移植肾存活情况等,并比较3组患者的恢复情况与术后并发症的差异。结果:15例受者术前群体反应性抗体(panel reactive antibody,PRA)与DSA均为阳性,均使用甲强龙+兔抗人胸腺细胞免疫球蛋白诱导治疗后行肾移植术。DCD未处理组术后均发生DSA水平反弹、移植肾功能延迟恢复(delayed renal graft function,DGF)与排斥反应,通过联合治疗后患者的DSA水平降低,移植肾功能恢复正常;DCD预处理组均未发生抗体反弹,1例受者出现DGF,接受血浆置换治疗后肾功能恢复正常,余4例受者均于术后2周内肾功能恢复至正常;LRD预处理组中2例发生DSA水平反弹,1例出现排斥反应,经治疗后移植肾功能均恢复至正常,DSA维持在低水平。DCD未处理组患者DGF、排斥反应的发生率高于DCD预处理组和LRD预处理组;术后血尿、蛋白尿、细菌真菌感染发生率及BK病毒感染率的差异均无统计学意义(均P>0.05)。在15例受者中,11例随访1年以上,6例3年以上,1例5年以上,受者和移植肾存活率均为100%。结论:经过有效的术前预处理进行脱敏治疗能够有效预防DSA阳性肾移植抗体反弹,减少围手术期并发症的发生。展开更多
文摘Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.
文摘Allo-antibodies, particularly when donor specific, are one of the most important factors that cause both early and late graft dysfunction. The authors review the current state of the art concerning this important issue in renal transplantation. Many antibodies have been recognized as mediators of renal injury. In particular donorspecific-Human Leukocyte Antigens antibodies appear to play a major role. New techniques, such as solid phase techniques and Luminex, have revealed these antibodies from patient sera. Other new techniques have uncovered alloantibodies and signs of complement activation in renal biopsy specimens. It has been acknowledged that the old concept of chronic renal injury caused by calcineurine inhibitors toxicity should be replaced in many cases by alloantibodies acting against the graft. In addition, the number of patients on waiting lists with preformed anti-human leukocyte antigens(HLA) antibodies is increasing, primarily from patients with a history of renal transplant failure already been sensitized. We should distinguish early and late acute antibody-mediated rejection from chronic antibody-mediated rejection. The latter often manifets late during the course of the posttransplant period and may be difficult to recognize if specific techniques are not applied. Different therapeutic strategies are used to control antibody-induced damage.These strategies may be applied prior to transplantation or, in the case of acute antibody-mediated rejection, after transplantation. Many new drugs are appearing at the horizon; however, these drugs are far from the clinic because they are in phase Ⅰ-Ⅱ of clinical trials. Thus the pipeline for the near future appears almost empty.
文摘AIM To analyze the clinical impact of preformed antiH LA-Cw vs antiH LA-A and/or-B donor-specific antibodies(DSA) in kidney transplantation.METHODS Retrospective study, comparing 12 patients transplanted with DSA exclusively antiH LA-Cw with 23 patients with preformed DSA antiH LA-A and/or B.RESULTS One year after transplantation there were no differencesin terms of acute rejection between the two groups(3 and 6 cases, respectively in the DSA-Cw and the DSA-A-B groups; P = 1). At one year, eG FR was not significantly different between groups(median 59 mL /min in DSA-Cw group, compared to median 51 mL /min in DSA-A-B group, P = 0.192). Moreover, kidney graft survival was similar between groups at 5-years(100% in DSA-Cw group vs 91% in DSA-A-B group, P = 0.528). The sole independent predictor of antibody mediated rejection(AMR) incidence was DSA strength(HR = 1.07 per 1000 increase in MFI, P = 0.034). AMR was associated with shortened graft survival at 5-years, with 75% and 100% grafts surviving in patients with or without AMR, respectively(Log-rank P = 0.005).CONCLUSION Our data indicate that DSA-Cw are associated with an identical risk of AMR and impact on graft function in comparison with "classical" class I DSA.
基金supported by grants from the National Natural Sciences Foundation of China (No. 30500468 and 30700768)
文摘The γc cytokines play an important role in proliferation and survival of T cells. Blocking the γc signals can cause the activated donor-reactive T cells losing the ability to proliferate, and getting into apoptosis pathway, which contributes to induction of the peripheral tolerance. In this study, we induced the transplant tolerance through blocking the γc in combination with donor-specific transfusion (DST) in the cardiac transplantation. Following DST, on the day 2, 4 and 6, C57BL/6 recipients received anti-γc monoclonal antibodies (mAbs) injection, and those in control group were not given anti-γc mAbs. On the day 7, Balb/c cardiac allografts were transplanted. All recipients in experimental group accepted cardiac allografts over 30 days, and two of them accepted allografts without rejection until sacrifice on the 120 day. Animals only receiving DST rejected grafts within 5 days, and the mice receiving cardiac transplantation alone rejected grafts within 9 days. Our study showed that blockade of γc signaling combined with DST significantly prolonged allograft survival, which was probably associated with inhibition of antigen-specific T-cell proliferation and induction of apoptosis.
文摘AIM To investigate the incidence, risk factors and clinical outcomes of acute antibody-mediated rejection(ABMR) after intestinal transplantation(ITx).METHODS A retrospective single-center analysis was performed to identify cases of acute ABMR after ITx, based on the presence of donor-specific antibody(DSA), acute tissue damage, C4 d deposition, and allograft dysfunction.RESULTS Acute ABMR was identified in 18(10.3%) out of 175 intestinal allografts with an average occurrence of 10 d(range, 4-162) after ITx. All acute ABMR cases were presensitized to donor human leukocyte antigens class Ⅰand/or Ⅱ antigens with a detectable DSA. A positive cross-match was seen in 14(77.8%) cases and twelve of 18 patients(66.7%) produced newly-formed DSA following ITx. Histological characteristics of acute ABMR include endothelial C4 d deposits, interstitial hemorrhage, and severe congestion with focal fibrin thrombin in the lamina propria capillaries. Multivariate analysis identified a liver-free graft and high level of panel reactive antibodyas a significant independent risk factor. Despite initial improvement after therapy, eleven recipients(61.1%) lost transplant secondary to rejection. Of those, 9(50%) underwent graft removal and 4(22.2%) received second transplantation following acute ABMR. At an average follow-up of 32.3 mo(range, 13.3-76.4), 8(44.4%) recipients died.CONCLUSION Our results indicate that acute ABMR is an important cause of intestine graft dysfunction, particularly in a liver-exclusive graft and survivors are at an increased risk of developing refractory acute rejection and chronic rejection. More effective strategies to prevent and manage acute ABMR are needed to improve outcomes.
基金Corresponding author:Lena Sibulesky,MD,Associate Professor,Surgeon,Department of Surgery,University of Washington Medical Center,UWMC 1959 NE Pacific St,Box 356410 Seattle,Seattle,WA 98195,United States.lenasi@uw.edu。
文摘BACKGROUND The liver has traditionally been regarded as resistant to antibody-mediated rejection(AMR).AMR in liver transplants is a field in its infancy compared to kidney and lung transplants.In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure(ALF)with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies(DSA).This case highlights the need for further investigations and heightened awareness for timely diagnosis.CASE SUMMARY A 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor.The recipient MELD at the time of transplant was 28.The flow cytometric crossmatches were noted to be positive for T and B lymphocytes.The patient had an uneventful recovery postoperatively.Starting on postoperative day 5 the patient developed fevers,elevated liver function tests,distributive shock,renal failure,and hepatic encephalopathy.She went into ALF with evidence of antibody mediated rejection with portal inflammation,bile duct injury,endothelitis,and extensive centrizonal necrosis,and C4d staining on allograft biopsy and elevated DSA.Despite various interventions including plasmapheresis and immunomodulating therapy,she continued to deteriorate.She was relisted and successfully underwent liver retransplantation.CONCLUSION This very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.
文摘AIM To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab in chronic-active antibody-mediated rejection(c AMR) settings.METHODS We compared 21 kidney transplant recipients(KTRs) with a diagnosis of c AMR in a retrospective casecontrol analysis: nine KTRs treated with plasmapheresis, intravenous immunoglobulins and rituximab(PE-IVIGRTX group) vs 12 patients(control group) not treated with antibody-targeted therapies. We examined kidney survival and functional outcomes 24 mo after diagnosis. Histological features and donor-specific antibody(DSA) characteristics(MFI and C1 q-fixing ability) were also investigated.RESULTS No difference in graft survival between the two groups was noted: three out of nine patients in the PE-IVIG-RTX group(33.3%) and 4/12 in the control group(33.3%) experienced loss of allograft function at a median time after diagnosis of 14 mo(min 12-max 18) and 15 mo(min 7-max 22), respectively. Kidney functional tests and proteinuria 24 mo after cA MR diagnosis were also similar in both groups. Only microvascular inflammation(glomerulitis + peritubular capillaritis score) was significantly reduced after PE-IVIG-RTX in seven out of eight patients(87.5%) in the PE-IVIG-RTX group(median score 3 in pre-treatment biopsy vs 1.5 in post-treatment biopsy; P = 0.047), without any impact on kidney survival and/or DSA characteristics. No functional or histological parameter at diagnosis was predictive of clinical outcome.CONCLUSION Our data showed no difference in the two year posttreatment outcome of kidney grafts treated with PE-IVIGRTX for c AMR diagnosis, however there were notable improvements in microvascular inflammation in posttherapy protocol biopsies. Further studies, especially involving innovative therapeutic approaches, are required to improve the management and long-term results of this severe condition.
基金Supported by The grant from the National Natural Science Foundation of China,No.81570588
文摘Antibody-mediated rejection(ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation(ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibodymediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients. Clearly, ABMR after ITx has become an important area for research and clinical investigation.
基金Supported by The Spanish Ministry of Economy,Instituto de Salud Carlos III,Nos.10/2332 and 11/857the Andalusian government,No.PI-0332-2007,for which Martinez-Bravo MJ was a pre-doctoral fellow
文摘AIM To investigate the role of glutathione S-transferase T1 donor-specific T lymphocytes in plasma cell-rich rejection of liver allografts.METHODS The study group included 22 liver transplant patients. Among them, 18 patients were mismatched for the glutathione S-transferase T1(GSTT1) alleles(don+/rec-), and 4 were matched(don+/rec+). Seven of the mismatched patients produced anti-GSTT1 antibodies and developed plasma cell-rich rejection(former de novo immune hepatitis). For the detection of specific Tlymphocytes, peripheral blood mononuclear cells were collected and stored in liquid nitrogen. The memory T cell response was studied by adding to the cell cultures to a mix of 39 custom-made, 15-mer overlapping peptides, which covered the entire GSTT1 amino acid sequence. The specific cellular response to peptides was analyzed by flow cytometry using the markers CD8, CD4, IL-4 and IFNγ.RESULTS Activation of CD8^+ T cells with different peptides was observed exclusively in the group of patients with plasma-cell rich rejection(3 out of 7), with production of IL-4 and/or IFNγ at a rate of 1%-4.92% depending on the peptides. The CD4^+ response was most common and not exclusive for patients with the disease, where 5 out of 7 showed percentages of activated cells from 1.24% to 31.34%. Additionally, two patients without the disease but with the mismatch had cells that became stimulated with some peptides(1.45%-5.18%). Highly unexpected was the finding of a double positive CD4^+CD8^(low) T cell population that showed the highest degree of activation with some of the peptides in 7 patients with the mismatch, in 4 patients with plasma cell-rich rejection and in 3 patients without the disease. Unfortunately, CD4^+CD8^(low) cells represent 1% of the total number of lymphocytes, and stimulation could not be analyzed in 9 patients due to the low number of gated cells. Cells from the 4 patients included as controls did not show activation with any of the peptides. CONCLUSION Patients with GSTT1 mismatch can develop a specific T-cell response, but the potential role of this response in the pathogenesis of plasma cell-rich rejection is unknown.
文摘目的:临床上预存供者特异性抗体(donor specific antibody,DSA)患者术后易发生抗体介导的排斥反应(antibody-mediated rejection,AMR),术后发生并发症和移植失败的风险相对较高。本研究旨在探讨DSA阳性肾移植临床治疗效果并分析术前预处理在DSA阳性肾移植中的作用与安全性,为临床DSA阳性肾移植提供单中心治疗经验。方法:回顾性分析郑州大学第一附属医院肾移植科的15例DSA阳性肾移植患者的临床资料,8例为公民逝世后器官捐献来源(organ donation after citizen’s death,DCD)肾移植受者,其中3例在术前未作脱敏治疗(DCD未处理组,n=3),5例受者在术前使用利妥昔单抗作脱敏治疗(DCD预处理组,n=5);其余7例为亲属活体供者(living related donors,LRD)肾移植受者,术前接受利妥昔单抗和血浆置换脱敏治疗(LRD预处理组,n=7)。收集受者肾功能,DSA水平变化,并发症发生情况,术后1年、3年及5年受者和移植肾存活情况等,并比较3组患者的恢复情况与术后并发症的差异。结果:15例受者术前群体反应性抗体(panel reactive antibody,PRA)与DSA均为阳性,均使用甲强龙+兔抗人胸腺细胞免疫球蛋白诱导治疗后行肾移植术。DCD未处理组术后均发生DSA水平反弹、移植肾功能延迟恢复(delayed renal graft function,DGF)与排斥反应,通过联合治疗后患者的DSA水平降低,移植肾功能恢复正常;DCD预处理组均未发生抗体反弹,1例受者出现DGF,接受血浆置换治疗后肾功能恢复正常,余4例受者均于术后2周内肾功能恢复至正常;LRD预处理组中2例发生DSA水平反弹,1例出现排斥反应,经治疗后移植肾功能均恢复至正常,DSA维持在低水平。DCD未处理组患者DGF、排斥反应的发生率高于DCD预处理组和LRD预处理组;术后血尿、蛋白尿、细菌真菌感染发生率及BK病毒感染率的差异均无统计学意义(均P>0.05)。在15例受者中,11例随访1年以上,6例3年以上,1例5年以上,受者和移植肾存活率均为100%。结论:经过有效的术前预处理进行脱敏治疗能够有效预防DSA阳性肾移植抗体反弹,减少围手术期并发症的发生。
