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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 1  |  Page : 31-36
Soluble CD30 in renal transplant recipients: Is it a good biomarker to predict rejection?


Organ Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

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Date of Web Publication8-Jan-2010
 

   Abstract 

It has been suggested that the serum soluble CD30 (sCD30) level may be a poten­tial marker for the prediction of acute allograft rejection in kidney transplant recipients. Therefore, its serum concentrations might offer a promising non-invasive tool to recognize patients with an increased risk for developing an acute graft rejection. We retrospectively correlate pre and post transplant level on post transplant graft survival, incidence of acute rejection and graft function using stored serum samples. Ninety-nine patients were divided in two separate groups: Group A in whom sample collection was done one day before transplantation and Group B where sample collection was done five days after transplantation. Younger recipients (aged less than 20 years) had higher sCD30 levels (P= 0.02). There was neither significant difference in the incidence of acute rejection nor incomplete response rate after anti rejection therapy in relation to pre trans­plant or post transplant sCD30. We could not find a significantly inferior graft survival rate in the high sCD30 group. In conclusion, younger patients had higher sCD30 concentrations however no correlation existed between the serum concentrations and occurrence of rejection episodes or graft survival.

How to cite this article:
Azarpira N, Aghdaie MH, Malekpour Z. Soluble CD30 in renal transplant recipients: Is it a good biomarker to predict rejection?. Saudi J Kidney Dis Transpl 2010;21:31-6

How to cite this URL:
Azarpira N, Aghdaie MH, Malekpour Z. Soluble CD30 in renal transplant recipients: Is it a good biomarker to predict rejection?. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Oct 26];21:31-6. Available from: https://www.sjkdt.org/text.asp?2010/21/1/31/58704

   Introduction Top


CD30 is a 120-kDa transmembrane glycopro­tein that belongs to the tumor necrosis factor and nerve growth factor receptor superfamily. [1] It is expressed on CD4 + and CD8 + activated T cells that secrete Th2-type cytokines. After ac­tivation of CD30 + T cells, a soluble form of CD30 (sCD30) is released into the blood stream, leading to the speculation that sCD30 levels may be closely related to CD30 expre­ssion on T cells and therefore serve as a mar­ker for immune activation. [2] Low serum levels of soluble CD30 were found in healthy humans, whereas increased sCD30 serum concentrations were detected under pathophysiological situa­tions such as systemic lupus erythematosus, rheumatoid arthritis, certain viral infections and adult T cell leukemia/lymphoma. [3] Identification of renal graft candidates at high risk of graft loss is an important part of pre-transplant eva­luation. Early recognition of acute rejections (AR) may help in treatment and avoidance of long term sequelae Currently, panel reactive antibodies (PRA) are generally accepted as the indicators of immunological status of renal graft candidates and the predictors of renal graft out­come. [4] Recently serum levels of sCD30 have received much attention. [5],[6],[7],[8],[9],[10],[11] Several reports show that elevated sCD30 levels, pre and post trans­plantation are associated with a poor prognosis for long term kidney graft survival. [12],[13],[14],[15],[16] These studies found higher sCD30 levels in allograft recipients and a good predictor of impending AR. Pelzl et al found that sCD30 measured on post-transplantation days 3 to 5 can offer a non­invasive means for recognizing patients with impending AR. [17] Based on these findings, we conducted a retrospective analysis on the effect of pre transplant and post transplant sCD30 in two separate groups of patients receiving kid­ney transplant. We evaluated the effect of sCD30 not only on incidence of AR but also on the responsiveness of anti rejection therapy and graft function at two years follow up.


   Material and Methods Top


96 patients underwent kidney transplantation from June 2005 to July 2006 at Shiraz Univer­sity Nemazi Hospital Transplantation Center were included in this study. Informed consent was obtained from each patient. The clinical characteristics related to transplantation and per­centage of PRA were retrieved from our Kid­ney Transplant Database. The sera of patients were collected and stored at -40°C. As there was controversial opinion about the best time for s CD30 measuring, we divided our patients in two separate groups. Group A: sample collec­tion was done one day prior to transplantation (n= 48) and Group B: 5 days after transplan­tation (n= 48). The detailed data of patients' demographic characteristics and pre-transplant status are shown in [Table 1] and [Table 2], which were comparable in two groups.

Exclusion criteria were PRA scores > 10%, previous allograft, delayed graft function (DGF), and infection episodes in the first month post­transplantation. Patients who needed dialysis during the first week without evidence of AR were diagnosed as DGF. The serum creatinine level (mg/dL) was used as a parameter of post transplant graft function and the response was categorized by serum creatinine levels after anti rejection therapy. The mean time for AR was 10-14 days. Biopsy-proven ARs were graded by the 97 Banff histological classifications. [18] Serum sCD30 content was measured using a commercially available enzyme-linked immuno­sorbent assay (Biotest AG, Dreieich, Germany). The sCD30 cutoff level of 100 U/mL was cho­sen on the basis of a previous study. [12] Pre­transplant virological serostatus was determined by assessment of CMV-IgG, EBV-VCA IgG, HBS Ag and HCV antibodies in the recipient respectively (ELISA kit, ABL, Germany). Graft loss was defined as patient death or conversion to maintenance dialysis. For the first line treat­ment of AR (either biopsy-proven or clinically treated), patients received methyl prednisolone pulse therapy (500 mg/day, for 5 days). The daily dose of cyclosporine was then adjusted according to the blood trough cyclosporine con­centration (C0); the target trough concentra­tion was 180 ng/mL. If there was no response to initial antirejection therapy, antilymphocyte antibody (OKT3) was used as a second line treatment. Patients enrolled were followed up for 2 years.


   Statistical Analysis Top


Data are expressed as means ±SD. The cor­relation between isolated parameters was esti­mated by Pearson's correlation coefficient, Chi­square and t tests. P< 0.05 was considered as significant. Analyses were performed with SPSS software (Statistical Package for the Social Sciences, version 15, SSPS Inc, Chicago, IL, USA).


   Results Top


Characteristics of Pre transplant sCD30 Level in group A

The mean sCD30 level was 130.3 ± 81.1 U/ mL (range 39- 400 U/mL). There was no signi­ficant difference in sCD30 level with respect to the gender of the recipient [Table 1]. Younger recipients (aged less than 20 years) showed significantly higher sCD30 levels, (291 ± 33.2 vs 125 ± 41.1U/mL), (P= 0.02). Among the patients with high pre transplant sCD30 Level (> 100 U/mL), 25% (5/20) had an underlying immunological disorders (three patients with systemic lupus erythematous and two patients with post infectious glumerulonephritis). sCD30 levels in two recipients with acute tubular nec­rosis (ATN), was < 100 U/mL.

Effect on Acute Rejection within the First Post transplant Month in Group A

The high sCD30 group showed a higher inci­dence of acute rejection within the post trans­plant one month than the low sCD30 group. However, this was not statistically significant (41% versus 33%, P> 0.05). One patient with re­ceived antithymocyte globulin (OKT3) and had high pre transplant sCD30 (128 IU/mL) levels. There was no significant correlation between incomplete response to anti-rejection treatment and pre transplant sCD30 levels (3/17; 17.6%), (P> 0.05).

Effect on Graft Survival Rate in Group A

During a mean of 24 months follow-up three allografts were lost (8.1%), (all of them by chronic rejection). There was no significant difference in the graft survival rate in relation to pre transplant sCD30 level (P> 0.05). About 30% of patients had at least one episode of bacterial urinary tract infection that was treated with antibiotics. One young patient de­veloped chicken pox and no confirmed fungal infection was detected.

Characteristics of Posttransplant sCD30 Level in Group B

The mean sCD30 level was 80.42 ± 35.1 U/mL (range 36-190 U/mL). There were no significant difference in sCD30 level with respect to the gender or age of the recipient (P= 0.83) [Table 2]. HBS Ag was detected in two patients' sera (sCD30 = 130 ± 3.1 IU/mL).

Effect on Acute Rejection within the First Post transplant Month in Group B

There was no correlation between sCD30 le­vel and incidence of AR. The high sCD30 group showed a 36% incidence of acute rejection within the post transplant one-month vs 34% in the low sCD30 group (P> 0.05). In addition, there was no significant correlation between incomplete response after anti-rejection and post transplant sCD30 level (2/18; 11.1%), (P> 0.05). Two patients received antithymocyte glo­bulin (OKT3), (CD30 level 80 ± 10.9 IU/mL).

Effect on Graft Survival Rate in Group B

During a mean of 24 months follow-up, three allografts were lost (all of them by chronic re­jection). There was no significant difference in the graft survival rate in relation to post trans­plant sCD30 level. Twenty-five percent of pa­tients developed urinary tract infection. A young patient developed mumps. There was no docu­mented fungal infection.


   Discussion Top


Our study in renal allograft recipients did not show any significant effect of sCD30 serum levels on AR or transplant survival. Besides PRA, recently, pretransplant sCD30 was intro­duced as an additional prognostic factor. [19],[20] We also confirmed like others that that renal allograft candidates also have higher pre trans­plant serum sCD30 levels than healthy people, which are predictive of early renal allograft loss. [17],[20] The recipient's age in our study corre­lated with pre transplant sCD30 similar to pre­vious results. [9],[22] We could not reproduce ear­lier studies showing higher pre transplant sCD30 level with acute vascular rejection and acute tubulointerstitial rejections and ATN characte­rized by decreased levels of sCD30. [23], The relatively superior overall graft survival rate (90% of two-year graft survival rate) and the relatively small-sized population in our study may cause such different results. Even though sCD30 were significantly higher in Group B (P< 0.001); there were also no significant co­rrelation between post transplant sCD30 and incidence of AR, incomplete anti rejection res­ponses and graft survival rate.

Our and other studies [10],[24] did not find signifi­cant differences between the pre-transplant se­rum sCD30 levels of patients with or without AR. Other studies rather point to an importance of sCD30 post-transplant monitoring for the prediction of allograft rejection/survival. [10],[16],[20],[24] Levels of sCD30 at day 5 [20],[24] post transplant was significant, nevertheless with different thres­hold values proposed by the authors does not allow any meaningful distinction between re­jecting and non-rejecting kidney recipients. CMV infections increased sCD30 levels with­in the first four post-transplant months, but not after 12 months. [3] Tacrolimus-based immuno­suppression resulted in a significant reduction of serum sCD30. [3] Therefore, interpretation of sCD30 as a biomarker must be done with cau­tion and all these identified markers should be kept in consideration before making any con­clusions.

Our study had few limitations. This study re­ferred to a limited number of patients, sCD30 levels as a prediction marker have only been determined once per patient and pre-transplan­tation accompanying post transplantation moni­toring of sCD30 levels over time has not been performed. Therefore, whether CD30 molecule is involved in acute allograft rejection and its role in allogeneic immune response needs fur­ther investigation.[25]

 
   References Top

1.Tarkowski M. Expression and a role of CD30 in regulation of T-cell activity. Curr Opin Hematol 2003;10(4):267-71.  Back to cited text no. 1      
2.Del Prete G, De Carli M, D'Elios MM, et al. CD30-mediated signaling promotes the deve­lopment of human T helper type 2-like T cells. J Exp Med 1995;182(6):1655-61.  Back to cited text no. 2      
3.Schlaf G, Altermann WW, Rothhoff A, Seliger B. Soluble CD30 serum level-an adequate marker for allograft rejection of solid organs? Histol Histopathol 2007;22(11):1269-79.  Back to cited text no. 3      
4.Gebel HM, Bray RA, Nickerson P. Pre­transplant assessment of donor-reactive, HLA­specific antibodies in renal transplantation: Contraindication vs. risk. Am J Transplant 2003;3(12):1488-500.  Back to cited text no. 4      
5.Pelzl S, Opelz G, Wiesel M, et al. Soluble CD30 as a predictor of kidney graft outcome. Transplantation 2002;73(1):3-6.  Back to cited text no. 5      
6.Susal C, Pelzl S, Dohler B, Opelz G. Identi­fication of highly responsive kidney transplant recipients using pretransplant soluble CD30. J Am Soc Nephrol 2002;13(6):1650-6.  Back to cited text no. 6      
7.Susal C, Pelzl S, Opelz G. Strong human leu­kocyte antigen matching effect in nonsense­tized kidney recipients with high pretransplant soluble CD30. Transplantation 2003;76(8): 1231-2.  Back to cited text no. 7      
8.Vaidya S, Partlow D, Barnes T ,Gugliuzza K. Pretransplant soluble CD30 is a better pre­dictor of post-transplantation development of donor-specific antibodies and acute vascular rejection than panel reactive antibodies, Trans­plantation 2006;82(12):1606-9.  Back to cited text no. 8      
9.Kim MS, Kim HJ, Kim SI, et al. Pretransplant soluble CD30 level has limited effect on acute rejection, but affects graft function in living donor kidney transplantation. Transplantation 2006;82(12):1602-5.  Back to cited text no. 9      
10.Slavcev A, Lacha J, Honsova E, et al. Soluble CD30 and HLA antibodies as potential risk factors for kidney transplant rejection. Transplant Immunol 2005;14:117-21.  Back to cited text no. 10      
11.Cinti P, Pretagostini R, Arpino A, et al. Eva­luation of pretransplant immunologic status in kidney-transplant recipients by panel reactive antibody and soluble CD30 determinations. Transplantation 2005;79(9):1154-6.  Back to cited text no. 11      
12.Altermann W, Schlaf G, Rothhoff A, Seliger B. High variation of individual soluble serum CD30 levels of pre-transplantation patients: sCD30 a feasible marker for prediction of kid­ney allograft rejection? Nephrol Dial Transplant 2007;22(10):2795-9.  Back to cited text no. 12      
13.Truong DQ, Darwish AA, Gras J, et al. Immuno­logical monitoring after organ transplantation: potential role of soluble CD30 blood level measurement. Transpl Immunol 2007;17(4): 283-7.  Back to cited text no. 13      
14.Wang D, Wu GJ, Wu WZ, et al. Pre- and post­transplant monitoring of soluble CD30 levels as predictor of acute renal allograft rejection. Transpl Immunol 2007;17(4):278-82.  Back to cited text no. 14      
15.Rodriguez LM, Paris SC, Arbelaez M, et al. Kidney graft recipients with pre-transplan­tation HLA CLASS I antibodies and high soluble CD30 are at high risk for graft loss. Hum Immunol 2007;68(8):652-60.  Back to cited text no. 15      
16.Giannoli C, Bonnet MC, Perrat G, et al. High pretransplantation soluble CD30 levels: impact in renal transplantation. Transplant Proc 2007; 39(8):2574-5.  Back to cited text no. 16      
17.Pelzl S, Opelz G, Daniel V, Wiesel M, Susal C. Evaluation of post-transplantation soluble CD30 for diagnosis of acute renal allograft rejection. Transplantation 2003;75(3):421-3.  Back to cited text no. 17      
18.Seron D, Moreso F, Bover J, et al. Early pro­tocol renal allograft biopsies and graft outc­ome. Kidney Int 1997;51(1):310-6.  Back to cited text no. 18      
19.Kennedy MK, Willis CR, Armitage RJ. Deci­phering CD30 ligand biology and its role in humeral immunity. Immunology 2006;118(2): 143-52.  Back to cited text no. 19      
20.Susal C, Pelzl S, Dohler B, Opelz G. Identi­fication of highly responsive kidney transplant recipients using pre-transplant soluble CD30, J Am Soc Nephrol 2002;13(6):1650-6.  Back to cited text no. 20      
21.Weimer R, Susal C, Yildiz S, et al. Post­transplant sCD30 and neopterin as predictors of chronic allograft nephropathy: impact of different immunosuppressive regimens, Am J Transplant 2006;6(8):1865-74.  Back to cited text no. 21      
22.Chen JY, Fu LS, Chu JJ, Chen HC, Chi CS. Plasma soluble CD30 level correlates negatively with age in children. J Microbiol Immunol Infect 2007;40(2):168-72.  Back to cited text no. 22      
23.Rajakariar R, Jivanji N, Varagunam M, et al. High pre-transplant soluble CD30 levels are predictive of the grade of rejection. Am J Transpl 2005;5(8):1922-5.  Back to cited text no. 23      
24.Dong W, Shunliang Y, Weizhen W, et al. Prediction of acute renal allograft rejection in early post-transplantation period by soluble CD30. Transpl Immunol 2006;16(1):41-5.  Back to cited text no. 24      
25.Seron D, Moreso F, Bover J, et al. Early protocol renal allograft biopsies and graft outcome. Kidney Int 1997;51:310-6.  Back to cited text no. 25      

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Correspondence Address:
Negar Azarpira
Organ Transplant Research Center Nemazi Hospital, Shiraz University of Medical Sciences Shiraz
Iran
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    Tables

  [Table 1], [Table 2]

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    Abstract
    Introduction
    Material and Methods
    Statistical Analysis
    Results
    Discussion
    References
    Article Tables
 

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