The common rejection module in chronic rejection post lung transplantation.
The common rejection module in chronic rejection post lung transplantation.
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DOI：
10.1371/journal.pone.0205107
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Sarwal MM
中科院分区：
文献类型：
--
作者：
Sacreas A;Yang JYC;Vanaudenaerde BM;Sigdel TK;Liberto JM;Damm I;Verleden GM;Vos R;Verleden SE;Sarwal MM
最近的研究表明，在不同的实体器官移植中存在类似的损伤机制，从而确定了一个共同的排斥模块（CRM），该模块由11个基因组成，这些基因在急性和较小程度上的慢性同种异体移植排斥反应中过表达。我们想评估CRM模块在识别急性排斥反应（AR）和慢性肺移植排斥反应（CLAD）的不同表型，即闭塞性细支气管炎综合征（BOS）和限制性同种异体移植综合征（RAS）方面的有用性，使用经支气管刷毛、支气管肺泡灌洗（BAL）样本和移植组织。通过qRT-PCR检测了11个CRM基因（CD6、TAP1、CXCL10、CXCL9、INPP5D、ISG20、LCK、NKG7、PSMB9、RUNX3和BASP1）在14个经支气管刷毛（AR, n = 4；无AR， n = 10）、32个BAL样本（稳定，n = 13； AR, n = 8； BOS, n = 9； RAS, n = 10）和44个组织样本（未使用供体肺，n = 15； BOS, n = 13； RAS, n = 16）中的基因表达。计算几何平均评分来量化免疫损伤的总体负担，并对肺移植损伤中最显著的基因建立新的计算模型。急性排斥反应在分析的几乎每个基因中都显示出显著差异，验证了先前微阵列分析的观察结果。RAS组织的几何平均评分（6.35）高于供体组织（4.09,p = 0.018）。单个CRM基因分析显示，ISG20、CXCL10和CXCL9在RAS中的表达增加。在BAL样本中，各组之间的基因表达或几何平均评分没有差异（stable, 5.15； AR, 5.81； BOS, 5.62； RAS, 7.31）。新建立的2基因组织CRM评分显示BOS和RAS之间没有任何差异（p < 0.05）。然而，该模型能够区分RAS和BOS组织（AUC = 0.75, 95% CI = 0.55-0.94, p = 0.025）。对CLAD中CRM基因的转录组织分析可以识别急性排斥反应，并将RAS与BOS区分开来。RAS的免疫激活似乎类似于肾/肝/心移植后的急性排斥反应。
Recent studies suggest that similar injury mechanisms are in place across different solid organ transplants, resulting in the identification of a common rejection module (CRM), consisting of 11 genes that are overexpressed during acute and, to a lesser extent, chronic allograft rejection. We wanted to evaluate the usefulness of the CRM module in identifying acute rejection (AR) and different phenotypes of chronic lung transplant rejection (CLAD), i.e., bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), using transbronchial brushings, broncho-alveolar lavage (BAL) samples, and explant tissue. Gene expression measurements for the 11 CRM genes (CD6, TAP1, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, and BASP1) were performed via qRT-PCR in 14 transbronchial brushings (AR, n = 4; no AR, n = 10), 32 BAL samples (stable, n = 13; AR, n = 8; BOS, n = 9; RAS, n = 10), and 44 tissue specimens (unused donor lungs, n = 15; BOS, n = 13; RAS, n = 16). A geometric mean score was calculated to quantitate overall burden of immune injury and a new computational model was built for the most significant genes in lung transplant injury. Acute rejection showed a significant difference in almost every gene analysed, validating previous observations from microarray analysis. RAS tissue demonstrated a higher geometric mean score (6.35) compared to donor tissue (4.09, p = 0.018). Analysis of individual CRM genes showed an increased expression of ISG20, CXCL10 and CXCL9 in RAS. In BAL samples, no differences were detected in gene expression or geometric mean scores between the various groups (stable, 5.15; AR, 5.81; BOS, 5.62; RAS, 7.31). A newly modelled 2-gene tissue CRM score did not demonstrate any difference between BOS and RAS (p>0.05). However, the model was able to discriminate RAS from BOS tissue (AUC = 0.75, 95% CI = 0.55–0.94, p = 0.025). Transcriptional tissue analysis for CRM genes in CLAD can identify acute rejection and distinguish RAS from BOS. The immune activation in RAS seems similar to acute rejection after kidney/liver/heart transplantation.
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DOI：
10.1111/ajt.12284
发表时间：
2013-07
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Keslar KS;Lin M;Zmijewska AA;Sigdel TK;Tran TQ;Ma L;Bhasin M;Rao P;Ding R;Iklé DN;Mannon RB;Sarwal MM;Strom TB;Reed EF;Heeger PS;Suthanthiran M;Fairchild RL
通讯作者：
Fairchild RL
影响因子：
8.9
作者：
Yusen, Roger D.;Edwards, Leah B.;Stehlik, Josef
通讯作者：
Stehlik, Josef
DOI：
10.1084/jem.20122709
发表时间：
2013-10-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Khatri P;Roedder S;Kimura N;De Vusser K;Morgan AA;Gong Y;Fischbein MP;Robbins RC;Naesens M;Butte AJ;Sarwal MM
通讯作者：
Sarwal MM
影响因子：
1.8
作者：
Mengual, Lourdes;Burset, Moises;Alcaraz, Antonio
通讯作者：
Alcaraz, Antonio
影响因子：
3.7
作者：
Shino MY;Weigt SS;Li N;Palchevskiy V;Derhovanessian A;Saggar R;Sayah DM;Huynh RH;Gregson AL;Fishbein MC;Ardehali A;Ross DJ;Lynch JP 3rd;Elashoff RM;Belperio JA
通讯作者：
Belperio JA