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AKR1B10作为2型麻风反应生物标志物和治疗靶点的潜力。

Potential of AKR1B10 as a Biomarker and Therapeutic Target in Type 2 Leprosy Reaction.

作者信息

Soares Cleverson T, Fachin Luciana R V, Trombone Ana P F, Rosa Patricia S, Ghidella Cássio C, Belone Andrea F F

机构信息

Department of Anatomic Pathology, Instituto Lauro de Souza Lima, Bauru, Brazil.

Department of Health Science, Universidade do Sagrado Coração, Bauru, Brazil.

出版信息

Front Med (Lausanne). 2018 Sep 24;5:263. doi: 10.3389/fmed.2018.00263. eCollection 2018.

Abstract

The (aldo-keto reductase family 1 member B10) gene has important functions in carcinogen-induced neoplasia. AKR1B10 is also expressed in type 2 reaction leprosy patients (R2). We measured the expression of AKR1B10 in the skin lesions of patients with leprosy by immunohistochemistry from biopsies that encompassed the spectrum of types of leprosy, based on the Ridley and Jopling classification [10 samples each of tuberculoid (TT), borderline tuberculoid (BT), mid-borderline (BB), and borderline lepromatous (BL) lesions; four samples of lepromatous lesions (LL)], reactional leprosy [14 samples of type 1 Reaction (R1) and 10 samples of type 2 Reaction (R2)], and biopsies from 9 healthy control (HC) subjects. In addition, 46 lepromatous lesions (BL and LL), 45 lepromatous lesions in regression, and 115 R2 lesions were included. Eight of 10 R2 samples (80%), 3 of 46 active BL and LL samples (6%), 23 of 45 BL and LL samples in regression (51%), and 107 of 115 R2 samples (93%) were positive for AKR1B10, differing significantly between all groups ( < 0.05). AKR1B10 expression was highest in the cytoplasm of macrophages. Thus, AKR1B10 is overexpressed on the lepromatous side (BL and LL) in samples that are in regression, especially type 2 reaction-associated lesions, rendering it a potential marker of type 2 reactional episodes of leprosy and a target of drugs against reactional episodes.

摘要

醛酮还原酶家族1成员B10(AKR1B10)基因在致癌物诱导的肿瘤形成中具有重要作用。AKR1B10在2型麻风反应患者(R2)中也有表达。我们根据里德利和乔普林分类法,通过免疫组织化学方法检测了涵盖各种麻风类型活检样本中麻风患者皮肤病变中AKR1B10的表达情况[结核样型(TT)、界线结核样型(BT)、中间界线型(BB)和界线类偏瘤型(BL)病变各10份样本;瘤型病变(LL)4份样本]、麻风反应[1型反应(R1)14份样本和2型反应(R2)10份样本],以及9名健康对照(HC)受试者的活检样本。此外,还纳入了46份瘤型病变(BL和LL)、45份消退期瘤型病变以及115份R2病变样本。10份R2样本中的8份(80%)、46份活跃的BL和LL样本中的3份(6%)、45份BL和LL消退期样本中的23份(51%)以及115份R2样本中的107份(93%)AKR1B10呈阳性,所有组之间差异有统计学意义(P<0.05)。AKR1B10在巨噬细胞胞质中表达最高。因此,AKR1B10在消退期样本的瘤型侧(BL和LL)尤其是与2型反应相关的病变中过度表达,使其成为麻风2型反应发作的潜在标志物以及针对反应发作的药物靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d55/6166685/90fdfb40e7f1/fmed-05-00263-g0001.jpg

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