Soluble CD30 concentrations in ESRD patients with and without panel reactive HLA antibodies

BACKGROUND: In this retrospective study we compared accuracy of panel reactive antibodies (PRA) with serum soluble CD30 (sCD30) contents in predicting acute rejection crisis post-renal transplant. METHODS: Pre-transplant sera from 115 patients were evaluated for their PRA and sCD30 concentrations. All patients received calcineurin inhibitor-based immunosuppressive therapy. Objective measurements for rejection were biopsy-proven acute rejection (AR) episodes within first six months of the transplant. Post-transplant sera of patients with AR were tested for the presence of donor-specific HLA antibodies (DSA). RESULTS: Overall AR rate was 16% (18/115). Patients positive for PRA and sCD30 tests were at significantly higher risk for AVR compared with those patients negative for both the tests (36% vs. 5%, p=0.01). Among negative PRA patients risk for AR was significantly elevated if they were also tested positive for sCD30 concentrations (21% vs. 5%, p=0.04). Of the 18 patients with AR, 14 were positive for sCD30, and 13 of them (93%) developed DSA post-transplant (p=0.001). CONCLUSION: These data showed that patients positive for sCD30 contents are at high risk for the development of DSA and AR post-transplant regardless of their pre-transplant PRA.     

Post-Transplant HLA class II Antibodies and High Soluble CD30 Levels are Independently Associated with Poor Kidney Graft Survival

HLA-specific antibodies (HSA) and soluble CD30 (sCD30) were measured in 208 renal transplant recipients with functioning grafts at least 1 year after transplantation (median 8.2 years) to investigate the predictive value of HSA and sCD30 on subsequent graft outcome. HSA (class I and class II) were detected by both ELISA LAT-M and Luminex LabScreen assays. Data on graft outcome was collected with a median follow-up time of 3.5 years after antibody and sCD30 measurement. Recipients with post-transplant HLA class II antibodies had particularly poor graft outcome with a hazard ratio (HR) of 7.8 (p < 0.0001) when detected by ELISA, and a HR of 6.0 (p < 0.0001) when detected by Luminex. A high post-transplant sCD30 level >or=100 U/mL was associated with increased risk of subsequent graft failure (HR 2.7, p = 0.03). sCD30 and HSA had an independent and additive association with graft outcome. Recipients with HLA class II antibody and high sCD30 had the highest risk of subsequent graft failure (HR 43.4, p < 0.0001 and HR 18.1, p = 0.0008 for ELISA and Luminex, respectively). These data show that detection of HSA and serum sCD30 measured at least 1-year post-transplant provides valuable and predictive information regarding subsequent graft outcome.     

Soluble CD30 and Hepatocyte growth factor as predictive markers of antibody-mediated rejection of the kidney allograft

Our retrospective study was aimed to assess the relevance of pre- and post-transplant measurements of serum concentrations of the soluble CD30 molecule (soluble CD30, sCD30) and the cytokine Hepatocyte growth factor (HGF) for prediction of the risk for development of antibody-mediated rejection (AMR) in kidney transplant patients. Evaluation of sCD30, HGF levels and the presence of HLA-specific antibodies in a cohort of 205 patients was performed before, 2 weeks and 6 months after transplantation. Patients were followed up for kidney graft function and survival for two years. We found a tendency of higher incidence of AMR in retransplanted patients with elevated pre-transplant sCD30 (≥ 100 U/ml) (p = 0.051), however no such correlation was observed in first-transplant patients. Kidney recipients with simultaneously high sCD30 and HLA-specific antibodies (sCD30+/Ab+) before transplantation had significantly lower AMR-free survival compared to the other patient groups (p < 0.001). HGF concentrations were not associated with the incidence of AMR at any time point of measurement, nevertheless, the combined analysis HGF and sCD30 showed increased incidence of AMR in recipients with elevated pretransplant sCD30 and low HGF levels. Conclusion: the predictive value of pretransplant sCD30 for the development of antibody-mediated rejection after transplantation is significantly potentiated by the co-presence of HLA specific antibodies. The role of HGF as a rejection-protective factor in patients with high pretransplant HGF levels would need further investigation.     

sCD30, interleukin-1beta-converting enzyme and anti-Annexin V autoantibodies concentrations in heart transplant recipients

sCD30 and ICE/caspase-1 as apoptosis-regulating factors are suspected to be involved in the survival rate of immunocompetent cells during immunosuppression after allotransplantation. Serum CD30 and ICE/caspase-1 concentrations were estimated and associated with unspecific serum apoptosis marker--anti-Annexin V antibodies and myocardial biopsies results. MATERIALS AND METHODS: 28 clinically stabile patients--heart transplant recipients at least 3 months after cardiac transplantation performed due to heart failure caused by ischaemic and/or congestive cardiomyopathy or/and primary valvular heart disease (26 men and 2 women, mean age=36.8 years, S.D.=7.6) with normal heart function assessed by use of ultrasound scan--were involved in the trial. The patients were divided and analyzed in two ways: first according to the results of elective endomyocardial biopsies and second to main immunosuppressive agent used. The enzyme immunoassay (CD30, Dako; interleukin-1beta-converting enzyme (ICE)/Caspase-1 ELISA and anti-Annexin V BENDER MedSystem) for soluble CD30, caspase-1 and anti-Annexin V autoantibodies serum levels was used. RESULTS: sCD30 and caspase-1 concentrations were non-significantly up-regulated in all analysed groups--with or without rejection signs or immunosuppressed with cyclosporine or especially tacrolimus. In contrast anti-Annexin V autoantibodies concentration was non-significantly down-regulated also in all studied groups. Moreover in the group with signs of transplant rejection, strong negative correlation between anti-Annexin antibodies and rejection grade was observed (-0.65, p<0.05). Biopsy results were comparable in groups treated with tacrolimus and cyclosporine A. CONCLUSIONS: The increasing tendency of sCD30 and caspase-1 as well as the decrease in anti-Annexin V autoantibodies concentrations in heart recipients could be the result of post-transplant apoptosis disturbances. This tendency seems to be inhibited in a greater degree by tacrolimus than by cyclosporine. Anti-Annexin V autoantibodies might be considered as negative rejection markers due to their strong negative correlation with the rejection grade.     

白细胞介素18受体和CD30抗原在移植肾组织中的表达

目的:探讨白细胞介素18受体(IL18R)和CD30抗原在移植肾排异反应中的局部表达及其临床意义。方法:采用链霉亲合素过氧化物酶(SP)免疫组织化学法检测44例移植肾切除标本[其中超急性排异反应(HAR)8例,急性排异反应(AR)16例,慢性排异反应(CR)12例和非免疫因素导致肾功能损害8例]及6例正常肾组织中IL18R和CD30的表达。结果:IL18R表达主要发生在肾小管上皮细胞,胞质表达为主。正常对照组肾小管上皮细胞表达为 ～ ,肾小球系膜细胞无表达。HAR、AR肾小管及肾小球的表达明显增强。CR组IL18R表达减弱。正常对照组肾小球、肾小管上皮细胞均无CD30抗原表达。HAR肾小球系膜细胞CD30( ),其余各组肾小球系膜细胞均无CD30抗原表达。CD30阳性均表现为胞质表达。肾小管上皮细胞CD30抗原表达多见于HAR和AR。CR及其他组肾小管上皮细胞CD30抗原表达较少。结论:IL18R和CD30抗原可能参与HAR、AR过程。检测IL18R和CD30抗原可为评价移植肾病理改变和肾移植预后提供重要参考。     

Pre- and post-transplant monitoring of soluble CD30 levels as predictor of acute renal allograft rejection

Identification of renal graft candidates at high risk of impending acute rejection (AR) and graft loss may be helpful for patient-tailored immunosuppressive regimens and renal graft survival. To investigate the feasibility with soluble CD30 (sCD30) as predictor of AR, sCD30 levels of 70 patients were detected on day 0 pre-transplant and day 1, 3, 5, 7, 10, 14, 21, and 30 post-transplant. AR episodes in 6 months were recorded and then patients were divided into Group AR (n=11) and Group UC (n=59). Results showed that the patients had higher pre-transplant sCD30 levels than healthy people. A significant decrease of sCD30 was observed on the first day post-transplant and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC (P<0.001). Patients of Group AR also had higher sCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 (P<0.001). The sCD30 level presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value. Therefore, sCD30 level may be a good marker of increased alloreactivity and of significant predictive value. It's necessary to monitor the variation of sCD30 in the early period post-transplant.     

苏木水提取物的抗急性排斥与Th1/Th2免疫偏移作用

目的探讨苏木水提取物在心脏移植中的免疫抑制作用及其机制。方法以W istar大鼠为供者、SD大鼠为受者,建立异位(腹腔)心脏移植模型。96只SD大鼠随机分为4组,每组24只。对照组:术前给橄榄油(8m l/kg.d);A组:给环孢菌素A(5m g/kg.d);B组:给苏木水提取物(37.5g/kg.d);C组:给苏木水提取物(25g/kg.d)+半量环孢菌素A(2.5m g/kg.d)。术后观察移植心的存活时间,心肌组织学和超微结构改变,术后3d和7d用逆转录-聚合酶链反应(RT-PCR)检测移植心脏白细胞介素-2(IL-2)信使核糖核酸(mRNA)、白细胞介素-10(IL-10)mRNA的表达,用酶联免疫吸附测定法(EL ISA)检测血清IL-2和IL-10的含量。结果与对照组比较,A组、B组、C组移植心存活时间延长(P<0.01),淋巴细胞浸润和心肌坏死程度较对照组轻,心肌IL-2mRNA表达较对照组减弱(P<0.01),IL-10mRNA表达较对照组增强(P<0.01)。A组术后3d和7d,B组、C组术后3d血清IL-2水平较对照组明显降低(P<0.01),A组术后7d,B组术后3d血清IL-10较对照组增高(P<0.05)。结论苏木水提取物在心脏移植后具有免疫抑制作用,可引起T h1向T h2免疫偏移。     

High variation of individual soluble serum CD30 levels of pre-transplantation patients: sCD30 a feasible marker for prediction of kidney allograft rejection?

BACKGROUND: Previous studies have suggested that the pre-transplant levels of the soluble CD30 molecule (sCD30) represent a non-invasive tool which can be used as a biomarker for the prediction of kidney allograft rejections. METHODS: In order to evaluate the feasibility of sCD30 for pre-transplantation monitoring the sera of potential kidney recipients (n = 652) were collected four times in a 3 months interval. Serum from healthy blood donors (n = 203) served as controls. The sCD30 concentrations of all samples were determined using a commercially available ELISA. This strategy allowed the detection of possible variations of individual sCD30 levels over time. RESULTS: Heterogeneous sCD30 concentrations were found in the samples obtained from individual putative kidney transplant recipients when quarterly measured over 1 year. Total 95% of serum samples obtained from healthy controls exhibited sCD30 values <30 U/ml, whereas most recipients displayed higher serum levels (>30 U/ml). Total 524 patients (80.4%) constantly exhibited serum concentrations of <100 U/ml during the period investigated, whereas 109 patients (16.7%) showed variations by exceeding the proposed 'cut off' of 100 U/ml for one to three times. The frequency of samples exhibiting sCD30 values >100 U/ml was significantly lower than that previously reported. CONCLUSIONS: The high degree of variation does not allow the stratification of patients into high and low immunological risk groups based on a single sCD30 value > 100 U/ml. Due to the heterogeneity of sCD30 levels during time course and the high values of SD, its implementation as a pre-transplant marker cannot be justified to generate special provisions for the organ allocation to patients with single sCD30 values > 100 U/ml.     

肾移植患者急性排斥反应与sCD30的相关性

目的 研究检测肾移植患者手术前后血清溶解性CD30（sCD30）水平的临床意义。方法 采用酶联免疫吸附剂测定法（ELISA）检测69例肾移植患者术前及术后sCD30的水平，并分析sCD30与肾移植受者术后急性排斥发生的关系。结果 术前sCD30阳性患者11例，其中有6例发生急性排斥，sCD30阴性患者58例，发生急性排斥5例。两组相比排斥反应发生率差异有统计学意义（P〈0．01）。术后5dsCD30在发生排斥患者组中的水平与对照组间差异有统计学意义（P〈0．05），而术后1、3d水平两组间差异无统计学意义（P〉0．05）。结论 肾移植手术前后监测sCD30水平，特别是术前及术后第5天左右时的检测水平，对于评估和预测急性排斥反应发生的可能性，具有重要的参考价值。     

Pre-transplant Th1 and post-transplant Th2 cytokine patterns are associated with early acute rejection in renal transplant recipients

In this retrospective study, we tried to define pre- and post-transplant immunological parameters that identify patients at risk for early acute rejection. Lymphocyte subpopulations and plasma levels of cytokines and neopterin were determined pre- and post-transplant in 32 renal transplant recipients with biopsy-proven early acute graft rejection. Recipients without early acute rejection served as controls. High pre-transplant interferon-gamma (IFN-gamma) plasma levels (p = 0.006), consistently high levels of neopterin early post-transplant (p = 0.008), a post-transplant switch from a Th1 to a Th2 cytokine pattern with decreasing IFN-gamma (p = 0.02), low CD8+ lymphocyte counts (p = 0.006) and consistently high CD19+ B lymphocyte counts were associated with acute rejection. Our data suggest that patients with a pre-transplant Th1 and an early post-transplant Th2 cytokine pattern are pre-disposed for early acute rejection.     

The Roles of CD8 Central and Effector Memory T-Cell Subsets in Allograft Rejection

The contribution of secondary lymphoid tissue-homing central memory T cells (T_CM) and peripheral tissue-homing effector memory T cells (T_EM) to allograft rejection is not known. We tested whether T_EM is the principal subset responsible for allograft rejection due to the nonlymphoid location of target antigens. Skin allograft rejection was studied after transferring either CD8 T_CM or T_EM to wild-type mice and to mice that lack secondary lymphoid tissues. We found that CD8 T_CM and T_EM were equally effective at rejecting allografts in wild-type hosts. However, CD8 T_EM were significantly better than T_CM at rejecting allografts in the absence of secondary lymphoid tissues. CD8 T_CM were dependent upon secondary lymphoid tissues more than T_EM for optimal differentiation into effectors that migrate into the allograft. Recall of either CD8 T_CM or T_EM led to accumulation of T_EM after allograft rejection. These findings indicate that either CD8 T_CM or T_EM mediate allograft rejection but T_EM have an advantage over T_CM in immune surveillance of peripheral tissues, including transplanted organs.     

Pre-transplant level of soluble CD30 is associated with infection after heart transplantation

BACKGROUND: One immunologic element of the immune system is the CD30 molecule which belongs to the TNF-R superfamily. CD30 can serve as a T-cell signal transducing molecule and is expressed by a subset of activated T lymphocytes, CD45RO(+) memory T cells. Augmentation of soluble CD30 during kidney transplant (Tx) rejection has been reported. Our study was to determine if the level of sCD30 prior to heart transplant (HTx) could categorize the patients (pts) into high or low immunologic risk for post-Tx outcome. METHODS: Pre-Tx sera from 100 consecutive HTx recipients were studied. sCD30 was detected by ELISA using the commercially available CD30 monoclonal antibody. Level of sCD30 was correlated with two-yr Tx outcome. RESULTS: Significant correlation was seen between the high level of sCD30 and lower incidence of infection. Four of the 35 pts with pre-Tx high level of sCD30 level (>90 U/mL) developed infection post-Tx. However, 31/65 pts who had a low level of sCD30 (<90 U/mL) developed infection post-transplantation (p < 0.0003). No remarkable differences were noted with the other clinical parameters, including mean hospitalization, 3A biopsy rejection or death. CONCLUSIONS: We report for the first time that the high level of sCD30 prior to the HTx may be associated with a higher immunologic ability of the pts and therefore, may have a protective effect in the development of infection post-Tx.     

Plasma levels of soluble CD30 are increased in children with chronic renal failure and with primary growth deficiency and decrease during treatment with recombination human growth hormone.

BACKGROUND: Previous studies have suggested that in vivo Th2 lymphocyte activation is related to increased soluble CD30 (sCD30) plasma levels. As various hormones (dehydroepiandrosterone, glucocorticoids, progesterone) can regulate the Th1/Th2 balance, and because growth hormone (GH) enhances lymphocyte function, we measured sCD30 plasma levels, before and after treatment with recombinant human GH (rhGH), in children with growth failure due to chronic renal failure (CRF) or to isolated GH deficiency in order to evaluate the potential effects of rhGH treatment on Th1/Th2 balance. METHODS: sCD30 plasma levels were determined by ELISA assay in 30 children with CRF (mean age 10.7+/-3.7 years), in five children with isolated GH deficiency (mean age 11.4+/-2.6 years), and in 10 normal controls (mean age 10.1+/-3.5 years). RESULTS: sCD30 levels were higher in the 30 children with CRF than in the 10 controls (179.8+/-79.4 vs 11.3+/-10.9 U/ml, P<0.001) exhibiting an inverse correlation with glomerular filtration rate (GFR) (r=-0.7860, P<0.001). In 11 children with CRF, after 19.9+/-16.7 months of rhGH treatment, a decrease of sCD30 plasma level (170+/-50 vs 134+/-49 U/ml, P<0.01) was observed. The five children with primary GH deficiency had higher sCD30 plasma level than controls (mean 147+/-105 vs 11+/-10 U/ml, P<0.004) and sCD30 plasma levels decreased to 95.2+/-109.6 U/ml after rhGH treatment. CONCLUSIONS: The finding that rhGH treatment decreased sCD30 plasma levels in children with CRF, and that children with primary GH deficiency had higher sCD30 plasma levels than controls, suggest that GH may regulate CD30 expression and possibly the balance of Th1/Th2. Whether the uraemia-induced increase in sCD30 is due to decreased renal excretion, to overproduction or both, remains to be determined.     

Absence of CD4CD25 regulatory T cell expansion in renal transplanted patients treated in vivo with Belatacept mediated CD28-CD80/86 blockade

AIMS: Belatacept is a new recombinant molecule (CTLA4-Ig) that interferes with the second activation signal of T lymphocytes. CTLA4-Ig induced T cell allograft tolerance in rodents but not in primates. We examined the changes in peripheral lymphocyte subsets, including regulatory T cells, in renal transplant patients treated with Belatacept. METHODS: A cross-sectional immunological study was carried out 6 months after transplantation in 28 patients enrolled in the Belatacept phase II study. Eighteen patients received Belatacept, mycophenolate mofetil and steroids (Belatacept group), while the control group of 10 patients received cyclosporine, mycophenolate mofetil and steroids (CsA group). Lymphocyte subsets were examined by flow cytometry. Foxp3 mRNA expression was measured by quantitative PCR. RESULTS: The number of T lymphocytes and the percentage of CD3+ T cells were similar in both groups. However, the percentage of CD3+ CD4+ T cells was lower in the Belatacept group than in the control CsA group (B=42.5%+/-13.7 vs CsA=52.9%+/-9, p<0.005), and the percentage of CD3+ CD8+ cells was higher in the Belatacept group than in the control (B=32.9%+/-6.7 vs CsA=19.5%+/-8.2, p<0.0002). The percentage of CD19+ cells was similar in both groups. Among CD56+cells, only the percentage of CD16+ cells was significantly higher in the Belatacept group than in the control (B=82%+/-12 vs CsA=59.7%+/-25, p=0.01). Among CD4 and CD8 T cells the percentage of activated lymphocytes expressing CTLA4, HLA-DR or CD40L was similar in both groups. The percentage of CD4+CD25+ T cells was higher in the CsA group. The percentage of regulatory CD4+CD25+ cells with bright CD25 staining was similar in both groups (B=3.6+/-2.3% vs CsA=4.7+/-1.9%, ns) as was the expression of FoxP3. CONCLUSION: Our results indicated that Belatacept did not induce regulatory T cell expansion in vivo. We suggest that Belatacept treatment should be maintained after transplantation to allow graft acceptance.     

Soluble CD30 and ELISA‐detected human leukocyte antigen antibodies for the prediction of acute rejection in pediatric renal transplant recipients

Biomarker‐based post‐transplant immune monitoring for the prediction of impending graft rejection requires validation in specific patient populations. Serum of 28 pediatric renal transplant recipients within the framework of a well‐controlled prospective randomized trial was analyzed pre‐ and post‐transplant for soluble CD30 (sCD30), a biomarker reflecting mainly T‐cell reactivity, and anti‐human leukocyte antigen (anti‐HLA) antibody reactivity, a biomarker for B‐cell activation. A sCD30 concentration ≥40.3 U/ml on day 14 was able to discriminate between patients with or without biopsy‐proven acute rejection (BPAR) with a sensitivity of 100% and a specificity of 76%. Six of seven patients (86%) with BPAR showed a sCD30 above this cut‐off, whereas only 3/21 patients (14%) without BPAR had a sCD30 above this cut‐off (P = 0.004). For pre‐ and post‐transplant anti‐HLA class II reactivities by enzyme‐linked immunosorbent assay, a cut‐off value of 140 optical density was able to discriminate rejecters from nonrejecters with a sensitivity of 86% or 71% and a specificity of 81% or 90%, respectively. Withdrawal of steroids was associated with a approximately twofold higher serum sCD30 compared to controls, but did not affect anti‐HLA reactivities. An increased post‐transplant sCD30 serum concentration and positive pre‐ and post‐transplant anti‐HLA class II reactivities are informative biomarkers for impending BPAR in pediatric renal transplant recipients. (TWIST, Clinical Trial No: FG‐506‐02‐43)     

肾移植受者术前血清可溶性CD30水平对急性排斥的影响

目的 研究术前血清可溶性CD30(sCD30)水平对肾移植受者术后6个月内急性排斥及排斥类型的预测作用。方法 共纳入自1998年12月至2003年8月在本中心行同种异体肾移植手术且存有术前血标本的707例受者。 回顾性总结该组受者术后6个月内急性排斥的发生情况及其它临床资料,同时选取健康对照40例。用sCD30 ELISA 试剂盒复孔检测肾移植受者术前和健康对照血清sCD30水平。根据术前sCD30水平将肾移植受者分为低sCD30组、中间sCD30组和高sCD30组。结果 肾移植组术前sCD30水平明显高于健康对照。血管性、细胞性排斥及临界改变的发生率随着sCD30水平的升高而升高(P均 < 0.05),但低、中、高sCD30 3组急性排斥逆转率却分别为100%、90.6%和78.6%,低sCD30组、中间sCD30组与高sCD30组比较差异均有统计学意义(P均 < 0.05)。血管性排斥、细胞性排斥、临界改变和临床排斥的sCD30水平[(198.95±76.09)、(165.89±44.56)、(172.94±74.22)和(161.23±64.87) U/ml]和未排斥组[(133.76±61.95) U/ml]比较,差异均有统计学意义(P均 < 0.01)。多因素logistic回归分析显示,高sCD30、群体反应性抗体(PRA)阳性和巨细胞病毒(CMV)抗原阳性均为急性排斥的危险因素,优势比分别为2.683、2.384和2.065。结论 术前高sCD30水平预示术后急性排斥发生率的增高。     

Immunological monitoring after organ transplantation: potential role of soluble CD30 blood level measurement

Analysing the relevance of soluble CD30 (sCD30) in the bloodstream before and after transplantation may be important for the monitoring of transplant recipients. In this study, 27 patients (15 pediatric liver and 12 adult kidney graft recipients) were investigated. In the liver graft group, the patients who developed acute rejection during the first month (n=9) had a slightly higher sCD30 value on pre-transplantation baseline (day 0) and post-transplantation day 7, when compared to patients with normal graft function (n=6) (day 0: 102(1.6) U/ml versus 118(1.5) U/ml, p=0.52) and (day 7: 69(1.5) U/ml versus 83(1.6) U/ml, p=0.47). Increased serum sCD30 was shown to correlate with increased interleukin-10 circulating levels between day 0 and day 7 (r=0.53; p=0.04), whereas, no correlation could be evidenced between interferon-gamma (IFN-gamma) and sCD30 (r=0.02; p=0.47). Similarly, in the kidney transplantation group, no significant difference was found in sCD30 levels at day 0 in both groups with graft rejection or normal graft function (n=6) (85(1.3) U/ml versus 77(1.6) U/ml, p=0.66), but sCD30 decreased significantly at day 7 post-transplantation from baseline value in the rejection group (n=6) (77(1.6) versus 35(1.4); p=0.02). We conclude that increased serum sCD30 was correlated with increased IL-10 (interleukin-10) circulating levels, but not with IFN-gamma levels in the post-transplantation period. Neither pre-transplantation sCD30 nor sCD30 at day 7 post-transplantation could be correlated with acute rejection in liver graft recipient. The monitoring of sCD30 might constitute a tool to assess the risk of acute rejection in renal transplant but did not appear as a valuable mean for early immunological monitoring in the small group of liver allograft recipients patients analysed in this study.     

RIP2 Is Required for NOD Signaling But Not for Th1 Cell Differentiation and Cellular Allograft Rejection

Two previous reports that receptor-interacting protein (RIP)-2 knockout (RIP2^–/–) mice had defective nuclear factor-kappa B (NF-κB) signaling and T helper (Th)1 immune responses had led us to believe that this putative serine-threonine kinase might be a possible target for transplant immunosuppression. Thus, we tested whether RIP2^–/– mice were able to reject vascularized allografts. Surprisingly, we found that T cells from RIP2^–/– mice proliferated and produced interferon (IFN)-γ after allostimulation in vitro . Moreover, naïve RIP2^–/– CD4⁺ T cells differentiated normally into Th1 or Th2 cells under appropriate cytokine microenvironments. Consistent with these findings, no difference in allograft survival was observed between wild-type and RIP2^–/– recipient mice, and rejection had similar pathology and cytokine profiles in both types of recipients. RIP2 deficiency was associated with defective NOD signaling, but this did not affect T-cell receptor (TCR)-dependent activation of the canonical NF-κB signaling or expression of NF-κB genes in rejecting allografts. Our data demonstrate that RIP2-deficient mice have intact canonical NF-κB signaling and can mount Th1-mediated alloresponses and reject vascularized allografts as efficiently as wild-type mice, thus arguing against RIP2 as a primary target for immunosuppression.     

肾移植患者术后外周血CD4+CD25+调节性T细胞的检测及其与瘦素水平的相关性

目的:了解肾移植患者术后外周血中CD4 CD25 调节性T细胞的比例和瘦素水平的变化及其临床意义,探讨CD4 CD25 调节性T细胞与瘦素水平的相关性。方法:应用放射免疫方法检肾移植患者及健康对照者外周血中瘦素的水平,流式细胞术检测外周血中CD4 CD25 调节性T细胞占CD4 T细胞的比例。结果:移植近期组(1年)与对照组患者血浆中瘦素浓度比较无差异,但移植远期组的瘦素浓度(2.5年)高于对照组和移植近期组。且外周血中CD4 CD25 调节性T细胞的比例与瘦素呈显著负相关(r=-0.83,P<0.01)。结论:肾移植术后的远期高瘦素血症可能对CD4 CD25 调节性T细胞具有负性调节作用,也许不利于移植耐受的维持。     

Inhibition of Acute Rejection After Skin or Cardiac Transplantation by Administration of Donor Antigens in the Rat

Purpose We examined differences in host immunologic changes induced by the intravenous or intraportal administration of donor antigens at engrafting and evaluated their contribution to graft survival using a rat transplantation model.Methods Lewis rat recipients were given either an intravenous or intraportal injection of donor splenocytes (1 × 10⁸) immediately after receiving skin grafts from Brown Norway donors. The immunologic responses were analyzed by mixed lymphocyte reaction (MLR) and profiles of interferon-, interleukin (IL)-2, and IL-10 in MLR supernatants. The effect on cardiac transplantation of perioperative administration of low-dose FK506 (0.1mg/kg per day) was also examined.Results Mixed lymphocyte reactions using splenocytes and sera from recipients treated intraportally were greatly inhibited. Interferon-, IL-2, and IL-10 levels were significantly higher after intraportal treatment compared with intravenous treatment (P 0.05). When FK506 was injected from day 3, a significant enhancement of cardiac allograft survival was demonstrated by intraportal treatment (16.1 ± 2.9 days) in comparison to the non-treatment (13.0 ± 1.7 days, P 0.05) and intravenous treatment rats (11.7 ± 2.7 days, P 0.05).Conclusions The Th2 deviation induced with intraportal alloantigen administration immediately after engraftment was thus observed to produce a synergistic effect with immunosuppressant treatment to suppress acute rejection.