Immunosuppressive therapy based on lymphocyte sensitivity in renal transplant patients

肾移植患者基于淋巴细胞敏感性的免疫抑制治疗

基本信息

批准号：
05671029
负责人：
KOZAKI Masami
金额：
$ 1.28万
依托单位：
Tokyo Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

1. Glucocorticoid Sensitivity in Peripheral-blood Lymphocytes of Chronic Renal FailureFour glucocorticoids, hydrocortisone (Cor), prednisolone (PSL), methylprednisolone (MPSL), and dexamethasone (Dex) were examined for their ability to suppress in vitro blastogenesis of mitogen-stimulated peripheral lymphocytes obtained from 134 chronic renal failure (CRF) patients waiting for renal transplantation and 102 healthy volunteers. Lymphocyte response to each glucocorticoid showed wide deviations among the subjects. PSL IC_<50> values of the CRF patients showed the largest deviation ranging from 1.0 to 10,000ng/ml. Thus, a significantly large population of the CRF patients (25.4%) when compared with the healthy subjects (3.6%), showed a marked decrease in lymphocyte response to PSL (p<0.01). The anti-lymphocyte potency of PSL assessed by IC_<50> of the steroid was less than that of Cor, whereas MPSL was >12-fold superior to PSL.It is concluded that MPSL could be of benefit to PSL-resistrant … More recipients, who can be identified by the preperative lymphocyte culture.2. Cyclosporine Sensitivity of Peripheral Blood Lymphocytes and Its Effect on Clinical Outcome in Renal Transplant Recipients.We estimated individual circrosporin (CYA) sensitivity by determining CYA concentration that would give 50% suppression of preoperative lymphocyteblastogenesis in vitro (IC_<50>), and then relationship between CYA sensitivity and clinical outcome was investigated retrospectively. Venous blood was taken from 31 renal transplant patients (19 males and 12 females) before CYA administration. These patients were divided into two groups based on their lymphocyte sensitivity to CYA,i.e., low sensitive (LS) group (IC_<50> of CYA higher than 10ng/ml) and high sensitive (HS) group (IC_<50> of CYA less than 10ng/ml). We estimated clinical efficacy of CYA by investigating incidence of acute rejection episode and changes of serum creatinine concetraion (S-Cr). Mean numbers of acute rejection episode occurred in LS group were 2.25<plus-minus>1.88 times/patient while those in HS group were 1.16<plus-minus>1.27 times. Thus, the incidence of acute rejection episode was tended to be fewer in HS group, though there was no statistical significance in the incidence between the groups. The mean S-Cr level gradually increased in LS group during 18 months after operation. The mean S-Cr level in LS groups at 18 months after transplantation was 2.90<plus-minus>2.29mg/dl, which was significantly higher than that of HS group (1.72<plus-minus>2.16mg/dl) (p<0.02). It is suggested that individualized immunosuppressive therapy with CYA based on both of phamacokinetic and pharmacodynamic views could be performed by determining CYA through level and lymphocyte sensitivity to CYA in combination. Less

1. 慢性肾功能衰竭的外周血淋巴细胞中的糖皮质激素敏感性检查了四种糖皮质激素：氢化可的松（Cor）、泼尼松龙（PSL）、甲基泼尼松龙（MPSL）和地塞米松（Dex）在体外抑制有丝分裂原刺激的外周细胞胚细胞发生的能力。从 134 名等待治疗的慢性肾衰竭 (CRF) 患者中获取的淋巴细胞肾移植和 102 名健康志愿者中，CRF 患者的淋巴细胞对每种糖皮质激素的反应显示出较大的偏差，范围为 1.0 至 10,000ng/ml。与健康受试者 (3.6%) 相比，CRF 患者 (25.4%) 的淋巴细胞对 PSL 的反应显着下降 (p<0.01)。通过类固醇的 IC_<50> 评估，PSL 的抗淋巴细胞效力低于 Cor，而 MPSL 比 PSL 优越 >12 倍。结论是，MPSL 可能对 PSL 抗性患者有益……更多，可以通过术前淋巴细胞培养来识别。2．肾移植受者外周血淋巴细胞对环孢素的敏感性及其对临床结果的影响。通过测定体外可抑制术前淋巴细胞胚细胞发生50%的CYA浓度(IC_<50>)来评估个体环孢素(CYA)敏感性，然后回顾性研究CYA敏感性与临床结果之间的关系。从31例肾移植中抽取静脉血。 CYA 给药前的患者（19 名男性和 12 名女性）根据淋巴细胞对 CYA 的敏感性分为两组，即低敏感（LS）组。 (CYA的IC_<50>高于10ng/ml)和高敏感(HS)组(CYA的IC_<50>低于10ng/ml)我们通过调查急性排斥反应的发生率和变化来评估CYA的临床疗效。血清肌酐浓度(S-Cr)平均发生急性排斥反应次数为2.25±1.88次/患者，而HS组为2.25±1.88次/患者。 1.16±1.27倍，因此，HS组的急性排斥反应发生率趋于较少，但各组之间的发生率无统计学意义，LS组的平均S-Cr水平逐渐升高。移植后18个月LS组平均S-Cr水平为2.90±2.29mg/dl，明显高于HS组。 (1.72±2.16mg/dl) (p<0.02) 建议根据药代动力学和药效学观点进行个体化的 CYA 免疫抑制治疗，通过结合 CYA 水平和淋巴细胞对 CYA 的敏感性来确定 CYA。。较少的