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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671029/
• 关键词: Renal Transplantation; Immunosuppression; Lymphocyte sensitivity; Glucocorticoid; Cicrosporin; Acute rejection; FK506; 薬剤選択; 免疫抑制剤投与法; 腎移植患者; グルココルチコイド; 急性拒絶反応

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。在慢性肾衰竭四方糖皮质激素，氢皮质酮（COR），泼尼松酮（PSL），甲基丙酮（MPSL）（MPSL）和右旋甲虫（Dex）的能力中，葡萄糖皮质酮（COR）和甲状腺甲醇（甲基甲醇）（甲基甲醇（pSL）（dex）的能力，糖皮质激素敏感性被抑制了13.等待肾移植和102名健康志愿者的慢性肾衰竭（CRF）患者。淋巴细胞对每种糖皮质激素的反应显示出受试者之间的广泛出发。 CRF患者的PSL IC_ <50>显示出最大的出发范围为1.0至10,000ng/ml。与健康受试者（3.6％）相比，CRF患者的人群显着较大（25.4％），显示出对PSL的淋巴细胞反应明显降低（P <0.01）。由IC_ <50>评估的PSL的抗淋巴细胞效力小于COR的抗淋巴细胞，而MPSL> 12倍高于PSL。得出的结论是，MPSL可能有益于PSL耐药的……更多的受益者，他们可以通过前疗程淋巴细胞培养物来鉴定出来的人。周围血液淋巴细胞的环孢子敏感性及其对肾脏移植受者中临床结果的影响。我们通过确定50％抑制术前术前淋巴细胞生成的cya浓度来估计单个孢子菌素（CYA）敏感性，该浓度将抑制50％抑制术前淋巴细胞生成型临床（IC_ <50> <50>），然后是CYA的关系。在CYA给药前，从31例肾脏移植患者（19名男性和12名女性）中获取静脉血。这些患者根据对CYA的淋巴细胞敏感性分为两组，即低敏感（LS）组（IC_ <50> CYA高于10ng/ml）和高灵敏度（HS）组（CYA的IC_ <50> CYA的IC_ <50>小于10ng/ml）。我们通过研究急性排斥发作的事件以及血清肌酐浓度（S-CR）的变化来估计CYA的临床效率。 LS组发生的急性排斥发作的平均数量为2.25 <plus-minus> 1.88次/患者，而HS组的患者为1.16 <plus-minus> 1.27次。这是HS组的急性拒绝事件事件往往更少，尽管两组之间的事件没有统计学意义。运行后18个月内LS组的平均S-CR水平逐渐增加。移植后18个月，LS组的平均S-CR水平为2.90 <plus-minus> 2.29mg/dl，其明显高于HS组（1.72 <plus-minus> 2.16mg/dl）（p <0.02）。有人建议，可以通过通过Phamacokinetic和Pharmacodynalnegication的CYA进行个性化免疫抑制治疗，可以通过通过水平来确定CYA和淋巴细胞对CYA的敏感性来进行组合。较少的

项目成果

Takeuchi H.: "Immunosupprressive therapy based on lymphocyte sensitivity in renal transplant patients" Byotaiseiri. 14. 401-404 (1995)

Takeuchi H.：“基于肾移植患者淋巴细胞敏感性的免疫抑制治疗”Byotaiseiri。

平野 俊彦: "慢性腎不全患者における末梢血リンパ球のグルココルチコイド感受性" Organ Biology.1. 61-69 (1994)

Toshihiko Hirano：“慢性肾功能衰竭患者外周血淋巴细胞的糖皮质激素敏感性”《器官生物学》61-69（1994）。

Toshihiko Hirano: "Clinical significance of glucocorticoid assessed by antilymphocyte action in kidney transplantation" Transplantation. 57. 1341-1348 (1994)

Toshihiko Hirano：“肾移植中通过抗淋巴细胞作用评估糖皮质激素的临床意义” 移植。

竹内 裕己: "リンパ球の薬剤感受性に基づく腎移植患者の合理的免疫抑制剤投与法" 病態生理. 14. 401-404 (1995)

Hiroki Takeuchi：“基于淋巴细胞药物敏感性的肾移植患者的合理免疫抑制剂给药方法”病理生理学 14. 401-404 (1995)。

竹内裕紀: "リンパ球の薬剤感受性に基づく腎移植患者の合理的免疫抑制剤投与法" 病態生理. 14. 401-404 (1995)

Yuki Takeuchi：“基于淋巴细胞药物敏感性的肾移植患者的合理免疫抑制剂给药方法”病理生理学 14. 401-404 (1995)。