肾移植急性排斥反应IL-15、穿孔素及颗粒酶B mRNA表达的实验与临床研究
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摘要
尽管近年来免疫抑制剂种类不断增加,但移植后急性排斥反应(acute rejection, AR)仍然是导致移植肾失功的重要原因。急性排斥反应的早期诊断及干预,对移植肾功能的恢复至关重要。虽然移植肾穿刺活检仍然是诊断的金标准,但大部分临床医生以及患者更愿意接受非侵袭性的诊断方法。随着对急性排斥反应分子生物学的深入研究,细胞因子在器官移植急性排斥反应的发生和发展中的作用受到广泛重视。移植术后对某些细胞因子的表达进行检测并干预以防治急性排斥反应是当前器官移植领域的研究热点。
已知白细胞介素2(IL-2)在肾移植AR中起重要作用,通过抑制IL-2受体(IL-2R)能有效的预防AR。但是即使如此,动物实验和临床移植中阻断IL-2/IL-2R仍不可能完全控制AR的发生,说明机体内存在有独立于IL-2/IL-2R系统之外的其他的T细胞激活途径。白细胞介素15(IL-15)是由单核细胞、树突状细胞等非T淋巴细胞分泌的细胞因子,最近的研究表明,它是CD8记忆T细胞增殖和活化的重要因子,在肝脏移植的急性排斥反应早期,可以检测到IL-15的表达高表达。穿孔素和颗粒酶B是细胞毒性T细胞分泌的因子,在急性排斥反应发生时被释放并攻击移植物。虽然对肾移植早期急性排斥反应时穿孔素(PFP)和颗粒酶B(GraB)的检测已有研究报道,但对于IL-15在肾移植AR发生时的作用以及它与PFP和GraB表达的关联性尚未见报道。本研究在动物实验和临床试验中探讨了IL-15、PFP和GraB在肾移植AR发生时的表达变化,以及IL-15在其中的作用。研究分三个部分:
第一部分建立大鼠同种异体肾移植模型
目的:建立稳定的同种异体大鼠肾移植模型,为开展大鼠肾移植相关研究奠定良好的实验基础。
方法:分别采用WISTAR大鼠和SD大鼠作为供受体,将供肾动脉带有的腹主动脉瓣与受体腹主动脉作端侧二定点外翻连续缝合;供体肾静脉带有的下腔静脉瓣与受体下腔静脉作端侧两定点外翻连续缝合。尿路重建采用供体输尿管膀胱瓣与受体膀胱吻合。
结果:手术总时间平均为(90±10)min。手术成功率为86%。
结论:此模型有较高的成功率和AR发生率,符合大鼠肾移植实验研究的需要。
第二部分阻断IL-15对大鼠肾脏移植急性排斥反应细胞毒性作用的研究
目的研究阻断IL-15对大鼠肾脏移植急性排斥反应细胞毒性作用的影响。
方法分别以WISTAR大鼠和SD大鼠作为供受体,建立大鼠同种异体肾移植模型。实验分四组(n≥15/组):(1)同基因移植组(对照组,Ctrl);(2)急性排斥反应(AR)组,术后无药物处理;(3)环孢素A(CsA)治疗组,术后经腹腔注射CsA针剂6mg.kg-1.d-1;(4)IL-15抗体(AB)治疗组,术后经腹腔注射IL-15抗体0.5mg/kg。以real-time PCR方法分别检测受体外周血和移植肾组织中IL-15、PFP和GraB的mRNA表达,并作移植肾AR病理学分析研究。
结果(1)AR、CsA及AB组术后移植肾组织及外周血中均出现IL-15、PFP和GraB mRNA表达水平上调,第3～5天达到高峰,第7天逐渐下降,与Ctrl组相比差异有统计学意义;(2)AR组与AB和CsA组比较,移植肾组织及外周血中IL-15、PFP和GraB mRNA表达均明显上调,差异有统计学意义(P<0.01),其中PFP和GraB mRNA表达上调较IL-15 mRNA更为明显(P<0.05);(3)AB组与AR组及CsA组比较,移植肾组织及外周血中IL-15 mRNA表达均明显降低,差异有统计学意义(P<0.05);(4)移植肾病理组织检查,Ctrl组和CsA组未见明显AR征象,AR组呈现重度AR反应,AB组AR征象较轻微。(5)三个细胞因子的表达变化在移植肾组织和外周血中差异无显著意义。
结论(1)AR发生早期IL-15、PFP和GraB在移植肾组织及外周血中均出现表达上调,IL-15可能是存在与IL-2之外的参与AR发生的另一途径;(2)AR发生时IL-15 mRNA的高表达与GraB和PFP的mRNA表达上调之间存在密切关联;(3)AR早期阻断受体内IL-15的表达,可降低GraB和PFP mRNA的表达,并抑制它们引起的细胞毒杀伤作用,从而保护移植物,减轻AR程度。(4)GraB、PFP和IL-15 mRNA的高表达可以作为诊断同种异体肾移植AR早期的重要指标。检测受体外周血中IL-15、PFP和GraB的mRNA表达水平,可以作为早期诊断AR的一种非侵袭性的检测方法。并且对判断AR的程度、治疗效果及预后均有一定的指导价值。
第三部分肾移植急性排斥反应患者血清白细胞介素15、穿孔素及颗粒酶B mRNA的表达
目的探讨IL-15、PFP和GraB mRNA检测在肾移植术后早期AR诊断及其与感染鉴别诊断中的价值。
方法采用SYBR Green I实时荧光定量逆转录聚合酶链反应(FQ-PCR)方法动态检测45例肾移植患者外周血淋巴细胞(PBL)中IL-15、PFP及GraB mRNA表达的变化。
结果:(1)AR组IL-15、PFP及GraB mRNA的表达均高于术前及肾功能稳定组(P<0.05),较临床症状出现早2～3天,经激素冲击治疗后,AR均得到逆转,同时PFP、GraB和IL-15 mRNA的表达减弱(P<0.05)。(2)与术前及肾功能稳定组比较,细菌感染组PFP和GraB mRNA的表达水平亦上升(P<0.05),抗感染治疗后表达水平下调。但IL-15 mRNA的表达水平均未见明显升高(P>0.05)。(3)CsA中毒组三项指标在监测过程中均未见明显变化。
结论
1. FQ-PCR动态测定PBL中IL-15、PFP及GraB mRNA表达是一种无创、较敏感的早期检测AR的方法,并可以预测抗AR的治疗效果。
2. IL-15作为CD8记忆T细胞生长和活化必须的细胞因子,可能是介导AR发生的重要因子。
3. IL-15 mRNA的表达水平在细菌感染发生时并不升高,而PFP和GraB却在患者发生AR和细菌感染时均有表达上调,因此同时检测这三个细胞因子,才能对AR和细菌感染作出鉴别诊断有价值。
The immunosuppression therapy has been improved greatly nowadays, but acute rejection is still a major cause for renal allograft loss. Early diagnosis and treatment are crucial to the restoration of allograft function after renal transplantation. Though fine-needle biopsy is the golden standard for accurate diagnosis, noninvasive methods are still preferred by many clinicians and patients. With the development of molecular biology, the role of cytokines in rejection is now paid much more attention. Now it’s hot to study the cytokine and cytotoxic molecule gene expressions and to intervene them during acute rejection.
It is well known that IL-2/IL-2R plays an important role during acute renal allograft rejection. In both human and animal experiments, anti-IL-2R antibody remarkably reduces the acute rejection rate, but there is still a portion of subjects who developed acute rejection. The facts implied there are other pathways which independent of IL-2/IL-2R system participated in acute rejection. IL-15 is produced by nonlymphoid cells including monocytes, dendritic cells and bone marrow stromal cells; it is a growth factor and an activator of CD8 memory T cells and was observed up-regulation during early liver acute rejection. Perforin and granzyme B are produced by CTL during acute rejection to attack the allograft. Although there are some reports about the perforin and granzyme B up-regulation during acute rejection of organ transplantation, the relationship between IL-15 and these two cytotoxic molecules are still unknown. In this study, we investigated the role of IL-15 in renal allograft rejection and the expressions of IL-15, perforin and granzyme B mRNA during renal acute rejection in both human and rats. The thesis is divided into three parts:
Part I: Establishment of a modified model of renal transplantation in the rat
0bjective : To establish a simple and reliable model of heterotopic renal allograft transplantation in rats.Providing a more practical and high acute rejection rate model for experimental studies of renal transplantation.
Methods:Using healthy adult WISTAR rats as donor and SD rats as recipient, Donor’s vena cava and a patch of aorta attached to renal artery was anastomosis end-side to the recipient’s vena cava and abdominal aorta. Ureter with bladder’s vane was suture to the recipient’s bladder.
Results:The average total time of operation was (90±10) min and the successful rate was 86%.
Conclusions:This is a feasible and reliable renal transplantation model with high acute rejection rate which is suitable for the study of organ transplantation mechanism in rats.
Part II: The study of the efficacy of blockading IL-15 to reduce the cytotoxic lymphocyte activity of acute renal allograft rejection in the rat
Objective To study the role of IL-15 in the process of acute rejection(AR) and investigate the efficacy of blockading IL-15 on the recipients to reduce the expressions of cytotoxic attack molecules granzyme B (GraB) and perforin (PFP) during acute renal allograft rejection in rats.
Methods Male Wistar rats and SD rats were used as donors and recipients, heterotopic renal transplantation model was established and four groups (n≥15/group) were involved in this study: (1). isograft group was used as the control group (Ctrl); (2). acute rejection group (AR) (received no treatment); (3). CsA treatment group (CsA) (received CsA 6mg.kg-1.d-1, i.p. posttransplant); (4) antibody treatment group (AB) (received anti IL-15 antibody 0.5mg/kg, i.p. on day 0, 2, 4 and 6 posttransplant). Animals were sacrificed on day 1, 3, 5 and 7 after transplantation. Allograft specimens and blood were collected. Allograft tissues were analyzed by pathologic assay and the expressions of IL-15, PFP and GraB mRNA in serum as well as renal tissues were detected by real-time polymerase chain reaction (real-time PCR).
Results (1). The expressions of IL-15, PFP and GraB mRNA were increased in groups AR, AB and CsA in both serum and tissue, respectively; compared to the Crtl group. The expressions reached highest points on day 3 or 5 and decreased on day 7, respectively; (2). In AR group, the expressions of IL-15, PFP and GraB mRNA were significantly higher in both serum and tissue than that of the other groups (P<0.01), and increased distinctly 3 days after transplantation, which about 2-3 days earlier than the appearance of clinical symptoms. (3). The expression of IL-15 mRNA in AB group was significantly lower compared to AR group and CsA group (P<0.05 ) . (4). The pathological results showed that the severe AR occurred on the 7th day after transplantation in group AR, respectively; whereas the rejection level were much mild in AB group. Ctrl group and CsA group showed no sign of AR.
Conclusions These data demonstrate that (1). The expressions of IL-15, PFP and GraB up-regulated early in the serum as well as tissue in rat renal AR model; IL-15 participated in the early stage of AR and the pathway maybe different from IL-2; (2). The up-regulation of PFP and GraB is related to the up-regulation of IL-15 in the early stage of AR; (3). Blocking IL-15 in the early stage of AR can down-regulate the expressions of PFP and GraB thus would have a promising results in control the progression of cytotoxic lymphocyte activity of acute renal allograft rejection in the rat; (4). Using real-time PCR to evaluate expressions of PFP、GraB and IL-15 may be a non-invasive as well as sensitive method to make an early diagnosis of acute allograft rejection and monitor the efficacy of anti-rejection therapy. Our findings might refine existing anti-rejection strategies.
Part III: Expressions of IL-15, perforin and granzyme B in peripheral blood during acute rejection of kidney transplantation
Objective To evaluate the value of IL-15, PFP and GraB in the early diagnosis and differential diagnosis of acute rejection(AR) after kidney transplantation. Methods Forty-five recipients of renal allograft were included in the study. The expressions of PFP, GraB and IL-15 mRNA were detected by SYBR Green I real time quantitative polymerase chain reaction (FQ-PCR).
Results The expressions of IL-15, PFP and GraB mRNA were increased significantly more in patients with AR (n=9) than those with stable renal function (n=23) and were about 2 to 3 days earlier than the appearances of clinical AR symptoms. After steroid therapy, all the AR was reversed and the expressions of PFP, GraB and IL-15 mRNA were decreasing at the same time. The expressions of PFP and GraB mRNA were also increased in cases of bacteria infection(n=8)but IL-15 mRNA remained unchanged. After the treatment of the infections, the expressions of PFP and GraB mRNA were down-regulated. The expressions of PFP, GraB and IL-15 mRNA had no significant difference in CsA-induced nephrotoxicity (n=5) during the study.
Conclusions Sequential monitoring the expressions of PFP, GraB mRNA combined with IL-15 mRNA in serum of renal allograft recipients can be as useful markers for the early diagnosis of AR and differential diagnosis from bacterial infection and it is valuable to observe the therapeutic effectiveness of AR after kidney transplantation. FQ-PCR had high sensitivity and reproducibility, it is suitable for clinical practice.
已知白细胞介素2(IL-2)在肾移植AR中起重要作用,通过抑制IL-2受体(IL-2R)能有效的预防AR。但是即使如此,动物实验和临床移植中阻断IL-2/IL-2R仍不可能完全控制AR的发生,说明机体内存在有独立于IL-2/IL-2R系统之外的其他的T细胞激活途径。白细胞介素15(IL-15)是由单核细胞、树突状细胞等非T淋巴细胞分泌的细胞因子,最近的研究表明,它是CD8记忆T细胞增殖和活化的重要因子,在肝脏移植的急性排斥反应早期,可以检测到IL-15的表达高表达。穿孔素和颗粒酶B是细胞毒性T细胞分泌的因子,在急性排斥反应发生时被释放并攻击移植物。虽然对肾移植早期急性排斥反应时穿孔素(PFP)和颗粒酶B(GraB)的检测已有研究报道,但对于IL-15在肾移植AR发生时的作用以及它与PFP和GraB表达的关联性尚未见报道。本研究在动物实验和临床试验中探讨了IL-15、PFP和GraB在肾移植AR发生时的表达变化,以及IL-15在其中的作用。研究分三个部分:
第一部分建立大鼠同种异体肾移植模型
目的:建立稳定的同种异体大鼠肾移植模型,为开展大鼠肾移植相关研究奠定良好的实验基础。
方法:分别采用WISTAR大鼠和SD大鼠作为供受体,将供肾动脉带有的腹主动脉瓣与受体腹主动脉作端侧二定点外翻连续缝合;供体肾静脉带有的下腔静脉瓣与受体下腔静脉作端侧两定点外翻连续缝合。尿路重建采用供体输尿管膀胱瓣与受体膀胱吻合。
结果:手术总时间平均为(90±10)min。手术成功率为86%。
结论:此模型有较高的成功率和AR发生率,符合大鼠肾移植实验研究的需要。
第二部分阻断IL-15对大鼠肾脏移植急性排斥反应细胞毒性作用的研究
目的研究阻断IL-15对大鼠肾脏移植急性排斥反应细胞毒性作用的影响。
方法分别以WISTAR大鼠和SD大鼠作为供受体,建立大鼠同种异体肾移植模型。实验分四组(n≥15/组):(1)同基因移植组(对照组,Ctrl);(2)急性排斥反应(AR)组,术后无药物处理;(3)环孢素A(CsA)治疗组,术后经腹腔注射CsA针剂6mg.kg-1.d-1;(4)IL-15抗体(AB)治疗组,术后经腹腔注射IL-15抗体0.5mg/kg。以real-time PCR方法分别检测受体外周血和移植肾组织中IL-15、PFP和GraB的mRNA表达,并作移植肾AR病理学分析研究。
结果(1)AR、CsA及AB组术后移植肾组织及外周血中均出现IL-15、PFP和GraB mRNA表达水平上调,第3～5天达到高峰,第7天逐渐下降,与Ctrl组相比差异有统计学意义;(2)AR组与AB和CsA组比较,移植肾组织及外周血中IL-15、PFP和GraB mRNA表达均明显上调,差异有统计学意义(P<0.01),其中PFP和GraB mRNA表达上调较IL-15 mRNA更为明显(P<0.05);(3)AB组与AR组及CsA组比较,移植肾组织及外周血中IL-15 mRNA表达均明显降低,差异有统计学意义(P<0.05);(4)移植肾病理组织检查,Ctrl组和CsA组未见明显AR征象,AR组呈现重度AR反应,AB组AR征象较轻微。(5)三个细胞因子的表达变化在移植肾组织和外周血中差异无显著意义。
结论(1)AR发生早期IL-15、PFP和GraB在移植肾组织及外周血中均出现表达上调,IL-15可能是存在与IL-2之外的参与AR发生的另一途径;(2)AR发生时IL-15 mRNA的高表达与GraB和PFP的mRNA表达上调之间存在密切关联;(3)AR早期阻断受体内IL-15的表达,可降低GraB和PFP mRNA的表达,并抑制它们引起的细胞毒杀伤作用,从而保护移植物,减轻AR程度。(4)GraB、PFP和IL-15 mRNA的高表达可以作为诊断同种异体肾移植AR早期的重要指标。检测受体外周血中IL-15、PFP和GraB的mRNA表达水平,可以作为早期诊断AR的一种非侵袭性的检测方法。并且对判断AR的程度、治疗效果及预后均有一定的指导价值。
第三部分肾移植急性排斥反应患者血清白细胞介素15、穿孔素及颗粒酶B mRNA的表达
目的探讨IL-15、PFP和GraB mRNA检测在肾移植术后早期AR诊断及其与感染鉴别诊断中的价值。
方法采用SYBR Green I实时荧光定量逆转录聚合酶链反应(FQ-PCR)方法动态检测45例肾移植患者外周血淋巴细胞(PBL)中IL-15、PFP及GraB mRNA表达的变化。
结果:(1)AR组IL-15、PFP及GraB mRNA的表达均高于术前及肾功能稳定组(P<0.05),较临床症状出现早2～3天,经激素冲击治疗后,AR均得到逆转,同时PFP、GraB和IL-15 mRNA的表达减弱(P<0.05)。(2)与术前及肾功能稳定组比较,细菌感染组PFP和GraB mRNA的表达水平亦上升(P<0.05),抗感染治疗后表达水平下调。但IL-15 mRNA的表达水平均未见明显升高(P>0.05)。(3)CsA中毒组三项指标在监测过程中均未见明显变化。
结论
1. FQ-PCR动态测定PBL中IL-15、PFP及GraB mRNA表达是一种无创、较敏感的早期检测AR的方法,并可以预测抗AR的治疗效果。
2. IL-15作为CD8记忆T细胞生长和活化必须的细胞因子,可能是介导AR发生的重要因子。
3. IL-15 mRNA的表达水平在细菌感染发生时并不升高,而PFP和GraB却在患者发生AR和细菌感染时均有表达上调,因此同时检测这三个细胞因子,才能对AR和细菌感染作出鉴别诊断有价值。
The immunosuppression therapy has been improved greatly nowadays, but acute rejection is still a major cause for renal allograft loss. Early diagnosis and treatment are crucial to the restoration of allograft function after renal transplantation. Though fine-needle biopsy is the golden standard for accurate diagnosis, noninvasive methods are still preferred by many clinicians and patients. With the development of molecular biology, the role of cytokines in rejection is now paid much more attention. Now it’s hot to study the cytokine and cytotoxic molecule gene expressions and to intervene them during acute rejection.
It is well known that IL-2/IL-2R plays an important role during acute renal allograft rejection. In both human and animal experiments, anti-IL-2R antibody remarkably reduces the acute rejection rate, but there is still a portion of subjects who developed acute rejection. The facts implied there are other pathways which independent of IL-2/IL-2R system participated in acute rejection. IL-15 is produced by nonlymphoid cells including monocytes, dendritic cells and bone marrow stromal cells; it is a growth factor and an activator of CD8 memory T cells and was observed up-regulation during early liver acute rejection. Perforin and granzyme B are produced by CTL during acute rejection to attack the allograft. Although there are some reports about the perforin and granzyme B up-regulation during acute rejection of organ transplantation, the relationship between IL-15 and these two cytotoxic molecules are still unknown. In this study, we investigated the role of IL-15 in renal allograft rejection and the expressions of IL-15, perforin and granzyme B mRNA during renal acute rejection in both human and rats. The thesis is divided into three parts:
Part I: Establishment of a modified model of renal transplantation in the rat
0bjective : To establish a simple and reliable model of heterotopic renal allograft transplantation in rats.Providing a more practical and high acute rejection rate model for experimental studies of renal transplantation.
Methods:Using healthy adult WISTAR rats as donor and SD rats as recipient, Donor’s vena cava and a patch of aorta attached to renal artery was anastomosis end-side to the recipient’s vena cava and abdominal aorta. Ureter with bladder’s vane was suture to the recipient’s bladder.
Results:The average total time of operation was (90±10) min and the successful rate was 86%.
Conclusions:This is a feasible and reliable renal transplantation model with high acute rejection rate which is suitable for the study of organ transplantation mechanism in rats.
Part II: The study of the efficacy of blockading IL-15 to reduce the cytotoxic lymphocyte activity of acute renal allograft rejection in the rat
Objective To study the role of IL-15 in the process of acute rejection(AR) and investigate the efficacy of blockading IL-15 on the recipients to reduce the expressions of cytotoxic attack molecules granzyme B (GraB) and perforin (PFP) during acute renal allograft rejection in rats.
Methods Male Wistar rats and SD rats were used as donors and recipients, heterotopic renal transplantation model was established and four groups (n≥15/group) were involved in this study: (1). isograft group was used as the control group (Ctrl); (2). acute rejection group (AR) (received no treatment); (3). CsA treatment group (CsA) (received CsA 6mg.kg-1.d-1, i.p. posttransplant); (4) antibody treatment group (AB) (received anti IL-15 antibody 0.5mg/kg, i.p. on day 0, 2, 4 and 6 posttransplant). Animals were sacrificed on day 1, 3, 5 and 7 after transplantation. Allograft specimens and blood were collected. Allograft tissues were analyzed by pathologic assay and the expressions of IL-15, PFP and GraB mRNA in serum as well as renal tissues were detected by real-time polymerase chain reaction (real-time PCR).
Results (1). The expressions of IL-15, PFP and GraB mRNA were increased in groups AR, AB and CsA in both serum and tissue, respectively; compared to the Crtl group. The expressions reached highest points on day 3 or 5 and decreased on day 7, respectively; (2). In AR group, the expressions of IL-15, PFP and GraB mRNA were significantly higher in both serum and tissue than that of the other groups (P<0.01), and increased distinctly 3 days after transplantation, which about 2-3 days earlier than the appearance of clinical symptoms. (3). The expression of IL-15 mRNA in AB group was significantly lower compared to AR group and CsA group (P<0.05 ) . (4). The pathological results showed that the severe AR occurred on the 7th day after transplantation in group AR, respectively; whereas the rejection level were much mild in AB group. Ctrl group and CsA group showed no sign of AR.
Conclusions These data demonstrate that (1). The expressions of IL-15, PFP and GraB up-regulated early in the serum as well as tissue in rat renal AR model; IL-15 participated in the early stage of AR and the pathway maybe different from IL-2; (2). The up-regulation of PFP and GraB is related to the up-regulation of IL-15 in the early stage of AR; (3). Blocking IL-15 in the early stage of AR can down-regulate the expressions of PFP and GraB thus would have a promising results in control the progression of cytotoxic lymphocyte activity of acute renal allograft rejection in the rat; (4). Using real-time PCR to evaluate expressions of PFP、GraB and IL-15 may be a non-invasive as well as sensitive method to make an early diagnosis of acute allograft rejection and monitor the efficacy of anti-rejection therapy. Our findings might refine existing anti-rejection strategies.
Part III: Expressions of IL-15, perforin and granzyme B in peripheral blood during acute rejection of kidney transplantation
Objective To evaluate the value of IL-15, PFP and GraB in the early diagnosis and differential diagnosis of acute rejection(AR) after kidney transplantation. Methods Forty-five recipients of renal allograft were included in the study. The expressions of PFP, GraB and IL-15 mRNA were detected by SYBR Green I real time quantitative polymerase chain reaction (FQ-PCR).
Results The expressions of IL-15, PFP and GraB mRNA were increased significantly more in patients with AR (n=9) than those with stable renal function (n=23) and were about 2 to 3 days earlier than the appearances of clinical AR symptoms. After steroid therapy, all the AR was reversed and the expressions of PFP, GraB and IL-15 mRNA were decreasing at the same time. The expressions of PFP and GraB mRNA were also increased in cases of bacteria infection(n=8)but IL-15 mRNA remained unchanged. After the treatment of the infections, the expressions of PFP and GraB mRNA were down-regulated. The expressions of PFP, GraB and IL-15 mRNA had no significant difference in CsA-induced nephrotoxicity (n=5) during the study.
Conclusions Sequential monitoring the expressions of PFP, GraB mRNA combined with IL-15 mRNA in serum of renal allograft recipients can be as useful markers for the early diagnosis of AR and differential diagnosis from bacterial infection and it is valuable to observe the therapeutic effectiveness of AR after kidney transplantation. FQ-PCR had high sensitivity and reproducibility, it is suitable for clinical practice.
引文
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