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个体淋巴细胞对类固醇的敏感性作为日本肾移植术后停用类固醇后临床结局的可靠生物标志物

Individual Lymphocyte Sensitivity to Steroids as a Reliable Biomarker for Clinical Outcome after Steroid Withdrawal in Japanese Renal Transplantation.

作者信息

Okihara Masaaki, Takeuchi Hironori, Kikuchi Yukiko, Akashi Isao, Kihara Yu, Konno Osamu, Iwamoto Hitoshi, Oda Takashi, Tanaka Sachiko, Unezaki Sakae, Hirano Toshihiko

机构信息

Department of Kidney Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji-shi, Tokyo 193-0998, Japan.

Department of Pharmacy, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.

出版信息

J Clin Med. 2021 Apr 13;10(8):1670. doi: 10.3390/jcm10081670.

DOI:10.3390/jcm10081670
PMID:33924724
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8070672/
Abstract

Recently, steroid reduction/withdrawal regimens have been attempted to minimize the side effects of steroids in renal transplantation. However, some recipients have experienced an increase/resumption of steroid administrations and acute graft rejection (AR). Therefore, we investigated the relationship between the individual lymphocyte sensitivity to steroids and the clinical outcome after steroid reduction/withdrawal. We cultured peripheral blood mononuclear cells (PBMCs) isolated from 24 recipients with concanavalin A (Con A) in the presence of methylprednisolone (MPSL) or cortisol (COR) for four days, and the 50% of PBMC proliferation (IC) values and the PBMC sensitivity to steroids were calculated. Regarding the experience of steroid increase/resumption and incidence of AR within one year of steroid reduction/withdrawal, the IC values of these drugs before transplantation in the clinical event group were significantly higher than those in the event-free group. The cumulative incidence of steroid increase/resumption and AR in the PBMC high-sensitivity groups to these drugs before transplantation were significantly lower than those in the low-sensitivity groups. These observations suggested that an individual's lymphocyte sensitivity to steroids could be a reliable biomarker to predict the clinical outcome after steroid reduction/withdrawal and to select the patients whose dose of steroids can be decreased and/or withdrawn after transplantation.

摘要

最近,人们尝试采用减少/停用类固醇的方案,以尽量减少类固醇在肾移植中的副作用。然而,一些受者出现了类固醇给药增加/恢复以及急性移植物排斥反应(AR)。因此,我们研究了个体淋巴细胞对类固醇的敏感性与减少/停用类固醇后的临床结果之间的关系。我们将从24名受者中分离出的外周血单个核细胞(PBMC)与伴刀豆球蛋白A(Con A)在甲泼尼龙(MPSL)或皮质醇(COR)存在的情况下培养四天,计算PBMC增殖的50%(IC)值以及PBMC对类固醇的敏感性。关于在减少/停用类固醇后一年内类固醇增加/恢复的情况以及AR的发生率,临床事件组中这些药物在移植前的IC值显著高于无事件组。移植前PBMC对这些药物高敏感组中类固醇增加/恢复和AR的累积发生率显著低于低敏感组。这些观察结果表明,个体淋巴细胞对类固醇的敏感性可能是一种可靠的生物标志物,可用于预测减少/停用类固醇后的临床结果,并选择移植后可以减少和/或停用类固醇剂量的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/d526818e7c81/jcm-10-01670-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/10f1c3a27202/jcm-10-01670-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/699e33169180/jcm-10-01670-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/b14c7fd70593/jcm-10-01670-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/aab1152358de/jcm-10-01670-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/0048b5524393/jcm-10-01670-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/d526818e7c81/jcm-10-01670-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/10f1c3a27202/jcm-10-01670-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/699e33169180/jcm-10-01670-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/b14c7fd70593/jcm-10-01670-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/aab1152358de/jcm-10-01670-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/0048b5524393/jcm-10-01670-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6638/8070672/d526818e7c81/jcm-10-01670-g006.jpg

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本文引用的文献

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Prospective nonrandomized study with early steroid withdrawal (Day 5) postrenal transplant in low immunological risk patients: A singlecenter experience at prince sultan military medical city Riyadh.低免疫风险患者肾移植术后早期停用类固醇(第5天)的前瞻性非随机研究:利雅得苏丹王子军事医疗城的单中心经验
Saudi J Kidney Dis Transpl. 2019 Nov-Dec;30(6):1398-1406. doi: 10.4103/1319-2442.275484.
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Racial disparity in kidney transplant survival relates to late rejection and is independent of steroid withdrawal.种族差异与肾移植存活率相关,与晚期排斥反应有关,且独立于类固醇撤药之外。
Clin Transplant. 2018 Sep;32(9):e13381. doi: 10.1111/ctr.13381. Epub 2018 Aug 30.
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Recurrence of IgA nephropathy after kidney transplantation in steroid continuation versus early steroid-withdrawal regimens: a retrospective analysis of the UNOS/OPTN database.
肾移植后类固醇维持与早期撤药方案对 IgA 肾病复发的影响:UNOS/OPTN 数据库的回顾性分析。
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Rapid Discontinuation of Prednisone in Kidney Transplant Recipients: 15-Year Outcomes From the University of Minnesota.肾移植受者中泼尼松的快速停用:明尼苏达大学的15年随访结果
Transplantation. 2017 Oct;101(10):2590-2598. doi: 10.1097/TP.0000000000001756.
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Steroid withdrawal after renal transplantation: a retrospective cohort study.肾移植后停用类固醇:一项回顾性队列研究。
BMC Med. 2017 Jan 12;15(1):8. doi: 10.1186/s12916-016-0772-6.
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A Comparative Effectiveness Analysis of Early Steroid Withdrawal in Black Kidney Transplant Recipients.黑人肾移植受者早期激素撤药的疗效比较分析。
Clin J Am Soc Nephrol. 2017 Jan 6;12(1):131-139. doi: 10.2215/CJN.04880516. Epub 2016 Dec 15.
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Early steroid withdrawal results in improved patient and graft survival and lower risk of post-transplant cardiovascular risk profiles: A single-center 10-year experience.早期停用类固醇可改善患者及移植物存活率,并降低移植后心血管风险状况:一项单中心10年经验。
Clin Transplant. 2017 Feb;31(2). doi: 10.1111/ctr.12878. Epub 2017 Jan 24.
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