公开(公告)号：US20150376723A1

公开(公告)日：2015-12-31

申请号：US14753266

申请日：2015-06-29

Applicant: University Health Network

Inventor： Shaf Keshavjee ,  Marcelo Cypel ,  Shahid Husain ,  Mingyao Liu

IPC: C12Q1/70

CPC classification number: C12Q1/701 ,  C12Q1/6883 ,  C12Q2600/158

Abstract: Described are biomarkers and associated methods for identifying a subject having, or at risk of developing, severe illness from influenza. The level of one or more biomarkers in a test sample from the subject is determined and compared to a control level. Optionally, the subject has or is suspected of having H1N1 influenza. In some embodiments the biomarkers may include IL23R, IL10, TNFRSF13B, CX3CR1, CCR2, MAP2K3 and/or IRF1. In some embodiments, the biomarkers include a combination of IL2 and IL23R or IL10 and IL23R. Also described are methods which include determining the level of two or more biomarkers in a sample and multivariate methods are used for comparing the levels in the test sample to the level in a control sample.

Abstract translation: 描述了用于识别具有或有发展为流感的严重疾病的风险的受试者的生物标志物和相关方法。 确定来自受试者的测试样品中的一种或多种生物标志物的水平并与对照水平进行比较。 任选地，受试者患有或怀疑患有H1N1流感。 在一些实施方案中，生物标志物可以包括IL23R，IL10，TNFRSF13B，CX3CR1，CCR2，MAP2K3和/或IRF1。 在一些实施方案中，生物标志物包括IL2和IL23R或IL10和IL23R的组合。 还描述了包括确定样品中两种或更多种生物标志物的水平的方法，并且多变量方法用于将测试样品中的水平与对照样品中的水平进行比较。

公开(公告)号：US20220341944A1

公开(公告)日：2022-10-27

申请号：US17413772

申请日：2019-12-13

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： Shafique Keshavjee ,  Mingyao Liu ,  Marcelo Cypel ,  Andrew Sage

IPC: G01N33/68 ,  G16B40/20 ,  G16H10/40 ,  G16H50/30

Abstract: Methods and kits for screening, diagnosing, detecting or predicting a patient outcome/risk variable for a lung transplant recipient after transplant or an EVLP outcome by measuring biomarker levels of at least three biomarkers selected from IL-6, IL-8, IL-10 and IL-1β optionally in combination with one or both of sTNFR1 and sTREM1 in EVLP perfusate are described. The methods involve for example, i. obtaining one or more test EVLP perfusate samples of a donor lung; ii. determining in one or more test EVLP perfusate sample of a donor lung, a polypeptide level of the at least three biomarkers selected from IL-8, IL-6, IL-10 and IL-1β and optionally one or both of sTNFR1 and sTREM1 i; and iii. a) comparing the one or more parameter values related to a level of the at least three biomarkers in the perfusate sample with control EVLP data or a cut-off level, wherein the differential level is indicative of outcome/risk of after transplant or of an EVLP outcome; or b) using the one or more parameter values related to a level of the at least three biomarkers in combination, as part of an algebraic calculation or model of outcome/risk.

公开(公告)号：US09835630B2

公开(公告)日：2017-12-05

申请号：US14768948

申请日：2014-02-20

Applicant: University Health Network

Inventor： Shaf Keshavjee ,  Marcelo Cypel ,  Mingyao Liu

IPC: G01N33/00 ,  G01N33/68 ,  C40B30/02

CPC classification number: G01N33/6884 ,  C40B30/02 ,  G01N33/68 ,  G01N2333/5754 ,  G01N2800/245

Abstract: A method of classifying a lung graft subjected to normothermic ex vivo lung perfusion (EVLP), during perfusion and/or after perfusion, the method comprising: a) collecting a test sample from the lung graft; b) measuring a polypeptide level of a negative transplant predictor gene product selected from CCG predictor gene products M-CSF, IL-8 SCGF-beta, GRO-alpha, G-CSF, MIP-1 alpha, and/or MIP-1beta, endothelin predictor gene products endothelin 1 (ET-1) and/or big ET-1, and/or apoptosis predictor gene products cytokeratin 18 (CK-18), caspase 3 and/or HMGB-1 in the sample and/or determining a metabolite profile of the sample for lung grafts that are from donors where the death was due to cardiac death (DCD); c) identifying the graft as a good candidate for transplant or a poor candidate for transplant wherein an increased polypeptide level of one or more negative transplant outcome predictor gene products compared to an outcome control or a reference metabolic profile is indicative the graft is a poor candidate for transplant.

公开(公告)号：US20150377904A1

公开(公告)日：2015-12-31

申请号：US14768948

申请日：2014-02-20

Applicant: UNIVERSITY HEALTH NETWORK

Inventor： Shaf Keshavjee ,  Marcelo Cypel ,  Mingyao Liu

IPC: G01N33/68 ,  C40B30/02

CPC classification number: G01N33/6884 ,  C40B30/02 ,  G01N33/68 ,  G01N2333/5754 ,  G01N2800/245

Abstract: A method of classifying a lung graft subjected to normothermic ex vivo lung perfusion (EVLP), during perfusion and/or after perfusion, the method comprising: a) collecting a test sample from the lung graft; b) measuring a polypeptide level of a negative transplant predictor gene product selected from CCG predictor gene products M-CSF, IL-8 SCGF-beta, GRO-alpha, G-CSF, MIP-1 alpha, and/or MIP-1beta, endothelin predictor gene products endothelin 1 (ET-1) and/or big ET-1, and/or apoptosis predictor gene products cytokeratin 18 (CK-18), caspase 3 and/or HMGB-1 in the sample and/or determining a metabolite profile of the sample for lung grafts that are from donors where the death was due to cardiac death (DCD); c) identifying the graft as a good candidate for transplant or a poor candidate for transplant wherein an increased polypeptide level of one or more negative transplant outcome predictor gene products compared to an outcome control or a reference metabolic profile is indicative the graft is a poor candidate for transplant.

Abstract translation: 一种在灌注和/或灌注后进行正常体温离体肺灌注（EVLP）分类的肺移植物的方法，所述方法包括：a）从肺移植物中收集测试样品; b）测量选自CCG预测基因产物M-CSF，IL-8 SCGF-β，GRO-α，G-CSF，MIP-1α和/或MIP-1beta的阴性移植预测基因产物的多肽水平， 内皮素预测基因产物内皮素1（ET-1）和/或大ET-1和/或凋亡预测基因产物细胞角蛋白18（CK-18），半胱天冬酶3和/或HMGB-1在样品中和/或确定 来自供体的肺移植物的样品的代谢物谱，其中死亡是由于心脏死亡（DCD）; c）将移植物鉴定为移植的良好候选者或用于移植的不良候选者，其中与结果对照或参照代谢特征相比，一种或多种阴性移植结果预测基因产物的多肽水平增加指示移植物是不良候选物 用于移植。

公开(公告)号：US20240251783A1

公开(公告)日：2024-08-01

申请号：US18565387

申请日：2022-03-08

Applicant: University Health Network

Inventor： Mingyao Liu ,  Shafique Keshavjee ,  Marcelo Cypel

IPC: A01N1/02

CPC classification number: A01N1/0226 ,  A01N1/0284

Abstract: Provided is a lung preservation composition comprising a non-carbonic buffered nutrient media, preferably a phosphate buffered nutrient media, and a dextran, optionally Dextran 40 and and optionally prostaglandin E1 (PGE1), and optionally at least one of alpha 1 antitrypsin (A1AT), an impermeant, optionally raffinose, an antioxidant, optionally glutathione, and necrostatin-1. Also described is a method of preserving a lung prior to and/or during transplant using said lung preservation composition, and kits comprising one or more components of the lung preservation composition.

公开(公告)号：US10000809B2

公开(公告)日：2018-06-19

申请号：US14769425

申请日：2014-02-20

Applicant: University Health Network

Inventor： Shaf Keshavjee ,  Mingyao Liu ,  Marcelo Cypel

IPC: G01N33/68 ,  C12Q1/68

Abstract: Methods for assaying a donor lung for chronic allograft lung dysfunction (CLAD) optionally bronchiolitis obliterans syndrome (BOS) subtype or restrictive allograft syndrome (RAS) subtype of CLAD or risk of developing BOS subtype or RAS subtype CLAD post-transplant, the method comprising: a. measuring a normalized expression level of an RNA transcript of IL-6 or an expression product thereof in a sample of the donor lung pre-transplant or a normalized expression level of one or more S100 protein, optionally S100A8 and/or S100A9, polypeptide expression product in a sample from the donor lung post-transplant; b. assessing the likelihood of the donor lung developing BOS subtype CLAD or RAS subtype CLAD post-transplant based on said IL-6, S100, optionally S100A8 and/or S100A9, expression level wherein IL-6 expression level is positively correlated with an increased likelihood of developing BOS post-transplant, S100A8 expression level is positively correlated with having or having an increased likelihood of developing RAS and/or BOS subtype CLAD, and S100A9 is positively correlated with having and having an increased likelihood of developing RAS subtype CLAD.