Role of TH1/TH2 Cytokines in Kidney Allograft Rejection

One of the major issues in contemporary kidney transplantation is prevention of acute allograft rejection episodes (AREs). Cytokines are crucial mediators of immune reactions leading to AREs. We correlated serum Th1/Th2 cytokine concentrations with AREs. The project included 44 patients undergoing kidney transplantation. During the 3-month period following the transplantation, ARE was diagnosed in 11 patients. Serum samples collected 1 day before and 2, 7, 14, and 30 days after transplantation were tested for interleukin (IL)-2, IL-4, IL-5, IL-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α concentrations using flow cytometry. Nonrejection (NONAR) and rejection (ARE) groups of patients did not show significant differences in baseline demographic characteristics. We observed that higher pretransplantation serum levels of IFN-γ (P = .000003) and IL-10 (P = .000001) were associated with AREs. Our analysis also showed slightly higher IL-4 serum levels among NONAR patients up to 7 days posttransplantation, followed by a drop in concentrations in NONAR patients. In contrast, there was a continuous increase among ARE patients. No significant differences were observed in plasma levels of IL-2, IL-5, IL-10, or TNF-α between the two groups. Higher pretransplantation levels of IFN-γ and IL-10 observed in ARE patients indicated ongoing nondetected, probably nonspecific, inflammatory processes able to intensify an immune response directed against the transplanted organ leading to its acute rejection. Higher levels of IL-4 prior to and shortly after transplantation may have protective effects on graft survival. However, a prolonged, increased production of IL-4 after transplantation can also contribute to AREs.     

Panel reactive HLA antibodies,soluble CD30 levels,and acute rejection six months following renal transplant

Domingues EMFL, Matuck T, Graciano ML, Souza E, Rioja S, Falci MC, Monteiro de Carvalho DB, Porto LC. Panel reactive HLA antibodies, soluble CD30 levels, and acute rejection six months following renal transplant.
Clin Transplant 2010: 24: 821–829. © 2009 John Wiley & Sons A/S. Abstract: Background: Specific anti‐human leukocyte antigen antibodies (HLA) in the post‐transplant period may be present with acute rejection episodes (ARE), and high soluble CD30 (sCD30) serum levels may be a risk factor for ARE and graft loss. Methods: HLA cross‐matching, panel reactive antibodies (PRA), and sCD30 levels were determined prior to transplantation in 72 patients. Soluble CD30 levels and PRA were re‐assessed at day 7, 14, 21, and 28, and monthly up to the sixth. Results: Twenty‐four subjects had a positive PRA and 17 experienced ARE. Nine of 17 ARE subjects demonstrated positive PRA and 16 had HLA mismatches. Positive PRA was more frequent in ARE subjects (p = 0.03). Eight subjects with ARE had donor‐specific antibodies (DSA) in serum samples pre‐transplantation, two subjects developed DSA. Three subjects without ARE had positive PRA only in post‐transplantation samples. Soluble CD30 levels were higher in pre‐transplant samples and ARE subjects than non‐ARE subjects (p = 0.03). Post‐transplant sCD30 levels were elevated in subjects who experienced rejection and were significantly higher at seven d (p = 0.0004) and six months (p = 0.03). Conclusions: Higher sCD30 levels following transplant were associated with ARE. Elevated sCD30 levels may represent a risk factor for acute rejection.     

Pretransplant soluble CD30 serum concentration does not affect kidney graft outcomes 3 years after transplantation

IntroductionAn elevated serum concentration of soluble the form of CD30 (sCD30), an activation marker of mainly T_H2-type cytokines producing T lymphocytes, has been reported as a predictive factor for acute cellular rejection episodes and poor graft outcomes in kidney transplantation. This historic cohort study investigated the association of a pretransplant sCD30 serum concentrations with kidney graft function and graft survival 3 years posttransplantation in adult recipients of deceased donor kidney grafts, treated with monoclonal anti-CD25 antibodies as an induction treatment combined with a cyclosporine (CsA)-based maintenance triple therapy.Materials and MethodsThe pretransplant sera of 296 recipients were tested for sCD30 content using a microsphere flow-cytometry assay. The estimated glomerular filtration rate (eGFR) was determined by the 4-variable Modification of Diet in Renal Disease equation. The incidences of graft loss were calculated with the use of Kaplan-Meier survival analysis and compared using the log-rank test.ResultsAccording to the distribution of the pretransplant sCD30 levels concentration ≥2700 pg/mL was defined as high (n = 146) and concentration <2700 pg/mL as low (n = 150). Three years posttransplantation, the eGFR was not significantly different in the recipients in high and low sCD30 groups (65 ± 24 vs 67 ± 21 mL/min/1.73 m²; P = .43); there was no association between the eGFR 3 years after transplantation and the pretransplant sCD30 levels (r² = 0.002; P = .49). Graft survival 3 years after transplantation was also not different in the recipients in high and low sCD30 groups (P = .52).ConclusionIn our adult deceased-donor kidney graft recipients, the pretransplant sCD30 serum concentration was not a predictive factor of immunologic risk associated with the kidney graft function 3 years posttransplantation; neither did it affect graft survival 3 years after transplantation. The immunosuppression with anti-CD25 antibodies as an induction treatment combined with the CsA-based maintenance triple therapy could possibly be decisive for our findings.     

Does pretransplant soluble CD30 serum concentration affect deceased-donor kidney graft function 3 years after transplantation?

Elevated serum concentrations of soluble CD30 molecule (sCD30) have been related to acute cellular rejection and poor graft outcomes in kidney transplantation. This historical cohort study investigated the association of pretransplant sCD30 serum concentrations with kidney graft function expressed as estimated glomerular filtration rate (GFR) at 3 years after transplantation. Pretransplant sera from 176 adult deceased-donor kidney graft recipients were tested for sCD30 content using a commercially available automated enzyme-linked immunosorbent assay. The immunosuppression consisted of induction therapy with monoclonal anti-CD25 antibodies and a maintenance regimen of cyclosporine (CsA)-based therapy. GFR was estimated (eGFR) by the four-variable Modification of Diet in Renal Disease (MDRD) Study equation. According to the distribution of pretransplant sCD30 levels (median 66.7 U/mL; interquartile range, 46.6 to 98.6 U/mL), a concentration of 66 U/mL or higher was defined as high (n = 89) and below 66 U/mL as low (n = 87). Three years after transplantation, eGFR was not significantly different among recipients in high versus low sCD30 groups (69 +/- 23 mL/min/1.73m2 vs 66 +/- 21 mL/min/1.73m2; P = .327) and there was no correlation between eGFR and pretransplant sCD30 levels (r2 = 0.001; P = .73). Upon multivariate regression analysis, donor age, recipient body mass index at transplantation, and acute rejection episodes were independent variables affecting eGFR at 3 years after transplantation. This study showed that pretransplant sCD30 serum concentrations were not associated with deceased-donor kidney graft function at 3 years after transplantation. The immunosuppression with anti-CD25 antibodies and a triple CsA-based maintenance regimen could possibly be decisive for our findings.     

Th1/Th2 Cytokines and Soluble CD30 Levels in Kidney Allograft Patients With Donor Bone Marrow Cell Infusion

Objective

We investigated the relevance of donor bone marrow cell infusion (DBMI) and serum levels of interferon-γ (IFN-γ), interleukin-10 (IL-10), and soluble CD30 (sCD30) in kidney recipients.

Patients and Methods

We analyzed the allograft outcomes correlated with sCD30, IFN-γ, and IL-10 levels using pre- and posttransplantation sera from 40 live donor renal transplants (20 patients with DBMI [2.1 × 10⁹ ± 1.3 × 10⁹ mononuclear cells/body] and 20 controls).

Results

Patients with acute rejection episodes (ARE)—3/20 DBMI and 6/20 controls—showed increased sCD30 and IFN-γ as well as decreased IL-10 posttransplantation compared with nonrejectors. Significant differences were observed for sCD30 and IFN-γ levels: 59.54 vs 30.92 ng/mL (P = .02) and 11.91 vs 3.01 pg/mL (P = .01), respectively. Comparison of pre- and posttransplant levels of IFN-γ, IL-10, and sCD30 in ARE patients showed higher levels in posttransplant sera except for IFN-γ in controls (6.37 vs 11.93; P = .01). Increased IFN-γ and IL-10 were correlated with rejection (r = .93; P = .008). sCD30 correlated with serum creatinine among ARE patients in control and DBMI groups (r = .89; P = .019; and r = 1.00; P < .0001, respectively).

Conclusions

Higher levels of sCD30, IFN-γ, and IL-10 posttransplantation in rejecting patients provided evidence for coexistence of cellular and humoral responses in ARE. There appeared to be a down-regulatory effect of infusion on alloresponses.     

Level of Soluble CD30 After Kidney Transplantation Correlates With Acute Rejection Episodes

Measurement of soluble CD30 (sCD30) levels may predict acute rejection episodes (ARE). To explore the value of sCD30 after transplantation, we tested serum sCD30 levels in 58 kidney transplant cases at 1 day before and 7 and 28 days after transplantation by enzyme-linked immunosorbent assay (ELISA). The incidences of ARE after kidney transplantation were recorded simultaneously. Meanwhile, 31 healthy individuals were selected as a control group. The results showed a relationship between sCD30 level in serum before kidney transplantation and the incidence of ARE. However, the relationship was more significant between serum sCD30 levels at day 7 after kidney transplantation and the incidence of ARE. There was no obvious relationship between serum sCD30 levels at day 28 after kidney transplantation and the incidence of ARE. These results suggested that the level of sCD30 at day 7 posttransplantation provides valuable data to predict ARE.     

Association of elevated pretransplant sCD30 levels with graft loss in 206 patients treated with modern immunosuppressive therapies after renal transplantation

BACKGROUND: Recent reports suggest that high pretransplant serum levels of soluble CD30 (sCD30) are a risk factor for rejections after kidney transplantation. The aim of our study was to elucidate the predictive value of pretransplant sCD30 levels for kidney transplantation outcome in a single-center patient cohort that has been treated with modern immunosuppressive therapies after transplantation. METHODS: We retrospectively analyzed sCD30 in multiple pretransplant sera from 206 patients, of whom 174 were transplanted with a cadaveric kidney and 32 patients received an allograft from a living donor. Renal function after transplantation was estimated by measuring serum creatinine and by rejection diagnosis. RESULTS: We could demonstrate a statistically significant association between increased pretransplant sCD30 values and graft failures (P=0.005). Receiver operating curve analysis revealed a cutoff value of 124 U/mL pretransplant sCD30. A multivariate analysis confirmed pretransplant sCD30 values >124 U/mL (P=0.011) and rejection episodes (P<0.0001) as independent risk factors for graft loss. CONCLUSION: Our study revealed a strong correlation between pretransplant sCD30 levels and the incidence of graft failure, but we could not confirm that the development of rejection episodes is correlated with pretransplant sCD30 values.     

Serum sCD30 in monitoring of alloresponse in well HLA-matched cadaveric kidney transplantations

In kidney transplantation, pretransplant serum sCD30 testing has been proposed in immunological risk estimation together with anti-HLA antibodies. We evaluated the risks associated with high pretransplant serum sCD30 in well HLA-matched cadaveric kidney recipients recruited in a clinical study comparing different immunosuppressive regimens. Rejection rate was similar in 37 recipients with high pretransplant serum sCD30 compared to 117 recipients with low serum sCD30 (16% vs. 15%, P=NS). Compared to pretransplant levels, the posttransplant sCD30 levels generally decreased, also in patients with rejection, although on day 21 posttransplant, rejecting patients had significantly higher relative sCD30 than nonrejecting patients (P<0.01). However, steroid-resistant rejection was associated with increasing posttransplant sCD30 levels. High pretransplant sCD30 values were associated with tubulointerstitial rejection. There was no correlation of sCD30 with delayed graft function. Good HLA matching seems to be effective in neutralizing the negative effect of a high pretransplant serum sCD30.     

Distinct Cytokine Patterns in Different States of Kidney Allograft Function

Cytokines are crucial inflammatory mediators involved in the development of immune response leading to allograft rejection. We investigated the cytokine patterns in patients sera from cases of acute rejection episodes (ARE), chronic rejection (CR), and long-term stable courses (STABLE). The project included 20 patients with ARE, 20 with CR, and 15 with at least a 5-year stable course. Serum samples collected at the time of rejection diagnosis were cytometrically tested for concentrations of interleukin (IL) 2, IL-4, IL-6, IL-10, interferon (IFN) γ, and tumor necrosis factor α. No significant differences between investigated groups were observed before transplantation (P > .05). Significant differences were observed among the groups in serum levels of IFN-γ, IL-4, IL-6, and IL-10. Our data suggested that distinct serum cytokine patterns were present among various states of kidney allograft function. ARE was characterized by a mixed cytokine pattern with elevated IL-10 and IFN-γ compared with the STABLE patients. The cytokine pattern in CR patients, in turn, was characterized by elevated levels of IL-4, IL-6, and IL-10 and decreased levels of IFN- γ compared with both STABLE and ARE subjects. Our results suggested that the T_H2 response may contribute to the initiation and/or maintenance of CR, because IL-4, IL-6, and IL-10 serve as growth and differentiation factors for B cells to increase antibody production. We also observed up-regulated production of IFN-γ and down-regulation of T_H2 cytokines among patients with stable long- term graft function.     

Identification of highly responsive kidney transplant recipients using pretransplant soluble CD30

The identification of high immunologic responders is desirable for the selection of appropriate immunosuppressive regimens. With the collaboration of 29 transplant centers in 15 countries, we investigated whether the pretransplant serum content of soluble CD30 (sCD30), a marker for the activation state of Th2-type cytokine producing T cells, is a useful predictor of kidney graft outcome. Pretransplant sera of 3899 cadaver kidney recipients were tested for serum sCD30 concentration using a commercially available enzyme-linked immunosorbent assay kit. Subsequent kidney graft survival was analyzed. The 5-yr graft survival rate in 901 recipients with a high pretransplant serum sCD30 (> or =100 U/ml) was 64 +/- 2%, significantly lower than the 75 +/- 1% rate in 2998 recipients with low sCD30 (<100 U/ml) (P < 0.0001). High sCD30 was associated primarily with graft loss and not with patient death. The sCD30 effect on graft survival was evident in first transplants as well as in retransplants, in presensitized patients with lymphocytotoxic antibodies as well as in nonsensitized patients, and in patients who received HLA well-matched kidneys as well as in patients who received poorly matched grafts. Recipients with a high pretransplant sCD30 needed significantly more rejection treatment after the first posttransplant year and continued to lose grafts at a higher rate during the 5-yr follow-up period, indicating that pretransplant sCD30 predicts not only the risk of acute rejection but also of chronic allograft nephropathy.     

Lipoxin A4 Attenuates Acute Rejection Via Shifting Th1/Th2 Cytokine Balance in Rat Liver Transplantation

Aims

To study the role of lipoxin A4 (LXA4) in rat liver transplant rejection.

Methods

An acute rejection model of liver transplantation was established in inbred rats DA to LEW that were randomly divided into a control group and a LXA4 group. Liver morphologic changes were examined using hematoxylin/eosin staining. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were quantified to measure liver injury. Intragraft mRNA and protein expressions of interferon (IFN)-γ interleukin and (IL)-10 were detected by real-time polymerase chain reaction and Western blots, respectively. The serum levels of IFN-γ and IL-10 were assayed by enzyme-linked immunosorbent assay.

Results

LXA4 treatment improved hepatic tissue injury as indicated by morphologic analysis. Serum ALT and AST levels were significantly decreased at day 7 post-transplantation (P < .05). Concurrently, expression of IFN-γ was downregulated (P < .05) and secretion of IL-10 was enhanced (P < .05).

Conclusions

LXA4 attenuated acute rejection with a parallel shift from Th1 to Th2 responses in rat liver transplantation.     

sCD30 and neopterin as risk factors of chronic renal transplant rejection: impact of cyclosporine A, tacrolimus, and mycophenolate mofetil

High pretransplantation sCD30 levels have been shown to be associated with lower 5-year kidney graft survival in mainly Cyclosporine A (CsA)-treated recipients (Collaborative Transplant Study database). To analyze the effect of different immunosupressive regimens (CsA/Azathioprine [Aza], CsA/Mycophenolate Mofetil [MMF], Tacrolimus [Tacr]/Aza) on sCD30, we assessed serum sCD30 and neopterin together with in vitro cytokine responses in a prospective randomized study of 84 renal transplant recipients before, 4 months, and 1 year after transplantation. Panel-reactive antibody (PRA) formation, HLA matching, ATG induction therapy, and acute rejections had no impact on sCD30 levels, whereas cytomegalovirus (CMV) infections induced an up-regulation of sCD30 4 months posttransplantation (P = .003). Whereas MMF showed no effect on sCD30 compared with Aza therapy, we found a significant impact of Tacr versus CsA treatment (1-year sCD30 ≥60 U/mL: 14/42 (33%), CsA; 1/38 (3%), Tacr; P < .0005). Chronic rejection 2 years posttransplantation was associated with elevated 1-year sCD30 (P = .001) and neopterin levels (P = .006). Our data indicate that the Th2 activation marker sCD30 provides a risk factor for chronic rejection independent of classical immunological risk factors and may be down-regulated using Tacr treatment.     

Pretransplant calcium levels have no predictive value for delayed graft function, long-term graft function, cardiovascular events, or graft and patient survival in renal transplantation

BACKGROUND: Disorders of calcium homeostasis are one of the most common problems in patients with end-stage renal disease (ESRD). Elevated calcium levels increase the incidence of cardiovascular mortality in ESRD patients, and appear to be a risk factor for the occurrence of delayed graft function (DGF) after kidney transplantation. Therefore, we investigated the impact of pretransplant serum calcium levels on outcomes after kidney transplantation: DGF, acute rejection, graft function, and survival, as well as the incidence of cardiovascular events. METHODS: We studied 285 patients (96.9% of all transplanted patients) who underwent their first transplantation between 1995 and 2004. Demographic data were extracted from hospital records or were documented during follow-up; serum samples were collected at the time of transplantation. RESULTS: In our cohort the incidence of DGF was 16.5% and 35.4% of acute rejection episodes (ARE). However, pretransplant calcium levels were not related to DGF or ARE in our patient cohort. Furthermore, there was no correlation between pretransplant serum calcium level with the incidence of cardiovascular events or mortality, as well as graft function or survival. CONCLUSION: In our study population pretransplant calcium levels showed no effect on DGF, ARE rate, the occurrence of cardiovascular events or death, renal graft function, or survival. Therefore, pretransplant calcium level is not a helpful marker for risk stratification at the time of transplantation.     

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。     

Plasma levels of soluble CD30 in kidney graft recipients as predictors of acute allograft rejection

In renal transplant recipients elevated soluble serum CD30 levels are associated with increased rejection and graft loss. We sought to determine the sCD30 plasma levels before and after kidney transplantation and to assess whether sCD30 was a predictive factor of immunological risk. sCD30 plasma levels were determined by an enzyme-linked immunosorbent assay assay in 52 kidney graft recipients before as well as 7, 15, and 21 days after transplantation. Eighteen patients developed acute allograft rejection (group I) and 34 patients showed uneventful courses (group II). Before transplantation sCD30 plasma levels were elevated in both groups (mean: 162.6 +/- 89.5 U/mL). After transplantation, group I recipients with acute rejection showed higher relative levels of plasma sCD30 on days 7 and 15 (120.8 +/- 74.6 U/mL and 210.6 +/- 108.7 U/mL respectively) compared with group II patients without rejection (95 +/- 45 U/mL and 59.4 +/- 31.6 U/mL), a difference that was significant for group I (P = .0003) and not significant for group II (P = .09). On day 21, sCD30 decreased in the two groups but remained higher among group I patients (120.6 +/- 92.7 U/mL). HLA antibodies were positive in 18 patients (34.6%) with 9 (50%) experiencing at last one episode of acute rejection. Among 34 patients negative for anti-HLA antibodies, nine displayed acute rejection only (26.4%), a difference that was not significant (P > .05). If we consider 100 U/mL as the minimum predictive level for allograft rejection, our results suggested that levels of sCD30 should be taken into consideration with the presence of HLA-antibodies detectable before and after transplantation, especially in patients with more than three HLA mismatches [RR = 3.20 (0.94 < RR < 10.91)]. These data suggested that measurement of plasma sCD30 is a useful procedure for the recognition of rejection in its earliest stages.     

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.     

Soluble CD30, Acute Rejection,and Graft Survival: Pre- and 6-Month Post-Transplant Determinations—When Is the Best Time to Measure?

Background

Pretransplantation soluble CD30 (sCD30) has been shown to be a good predictor of acute rejection (AR) and graft loss. This study aimed to evaluate the effectiveness of sCD30 measured pretransplant and up to 6 months after transplantation as a predictor of AR, graft loss, and survival at 5 years post-transplantation. Subjects were patients receiving living donor renal transplants at Bonsucesso Federal Hospital (Rio de Janeiro) in 2006 and between August 2010 and May 2011.

Soluble CD30 and HLA antibodies as potential risk factors for kidney transplant rejection

Recent literary data suggest that high pre- and post-transplant serum levels of the soluble CD30 (sCD30) molecule may be a risk factor for acute rejection and worse prognosis of the transplanted kidney. The aim of our study was to correlate the concentrations of sCD30 and the presence of HLA antibodies as defined by flow cytometry and ELISA with the clinical course and graft prognosis after transplantation. One hundred and seventeen kidney transplant patients were included into the study. The incidence of rejection episodes, graft function and graft survival for up to 1 year post-transplant were evaluated. Soluble CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. In both patient groups, a significant decrease of sCD30 was detected 2 weeks after transplantation (104.4 U/ml before vs. 37.0 U/ml post-transplant, P < 0.001). However, there was a substantial difference in the level of decrease of sCD30 between rejecting and non-rejecting patients. Patients without rejection had lower sCD30 values (31.2 U/ml post-transplant) compared to patients who experienced rejection episodes (62.9 U/ml), P < 0.04. Multifactorial analysis showed that antibodies to HLA class II antigens and elevated concentrations of sCD30 shortly after transplantation were associated with increased risk for acute rejection in the first post-transplant year. Measurement of soluble CD30 after transplantation, taken into consideration with the presence of HLA class II antibodies, might be helpful for evaluating the potential risk for acute rejection.     

High Serum Level of the Soluble CD30 Identifies Chinese Kidney Transplant Recipients at High Risk of Unfavorable Outcome

Background

We sought investigate the relationship between serum level of sCD30 and recipient/graft survival rates, rejection types, as well as other prognostic factors among Chinese kidney transplant patients.

Materials and methods

We performed enzyme-linked immunosorbent assays of serum sCD30 levels in duplicate among retrospective cohort of 707 renal transplant patients.

Results

The incidences of rejection increased in relation to the pretransplant sCD30 level. The reversal rates of rejection were 100%, 90.6%, and 78.6% for the low, intermediate, and high sCD30 groups. This observation suggested that high levels of sCD30 and pretransplant panel-reactive antibody (PRA)-positive patients are risk factors for acute rejection with odds ratios of 6.862 and 1.756. High sCD30 was an independent risk factor for functional graft survival. The 5-year graft survival rates were 99.39% ± 6.1%, 93.11% ± 1.93%, and 82.07% ± 3.97% among the low, intermediate, and high sCD30 groups, while the 5-year recipient survival rates were 89.25% ± 2.41%, 91.82% ± 1.64%, and 88.85% ± 2.36%, respectively. Increased sCD30 levels were observed among patients who were PRA-positive, cytomegalovirus antigens or antibodies positive, on long-term dialysis, and ≤ 20 years old.

Conclusions

Pretransplant sCD30 serum levels reflect immune status.