Expression of the Autoantigen Topoisomerase-1 is Enriched in the Lung Tissues of Patients With Autoimmune Interstitial Lung Disease: A Case Control Study.
Expression of the Autoantigen Topoisomerase-1 is Enriched in the Lung Tissues of Patients With Autoimmune Interstitial Lung Disease: A Case Control Study.
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DOI：
10.1002/acr2.11191
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发表时间：
2020-11
影响因子：
3.4
通讯作者：
McMahan ZH
中科院分区：
文献类型：
--
作者：
Cottrell TR;Askin F;Halushka MK;Casciola-Rosen L;McMahan ZH
在自身免疫性风湿性疾病中，针对普遍表达的蛋白(如拓扑异构酶-1)的自身抗体与特定的临床并发症(如间质性肺病[ILD])有关。已有研究表明，炎症靶组织中丰富的抗原表达可能在集中自身免疫反应中发挥作用。我们试图确定相对于正常肺，拓扑异构酶-1在自身免疫性/炎症性疾病患者的肺中是否表达丰富。我们使用包含40例自身免疫性炎症性ILD(病例)和46例正常肺组织的99核心肺组织芯片(TMA)。我们用抗体对TMA进行染色，以比较患者和对照组之间拓扑异构酶-1和CD8的表达，并评估是否在特定类型的细胞中表达丰富。对染色结果进行分析，并进行统计学比较。拓扑异构酶-1在肺泡细胞(47%比16%；P=0.003)和基质/免疫细胞(32%比5%；P=0.002)中的整体表达高于对照组(53%比21%；P=0.002)。拓扑异构酶-1阳性肺组织中CD8细胞密度(223个/mm~2)显著高于拓扑异构酶-1阴性肺组织(102个/mm~2；P=0.018)。有趣的是，拓扑异构酶-1在硬皮病中的表达显著高于正常肺(67%比21%；P=0.036)，在这些患者的肺泡细胞中表达更频繁(67%比16%；P=0.018)。与正常肺相比，自身免疫性ILD肺组织中拓扑异构酶-1的表达增加，尤其是在肺泡细胞中。这可能导致对拓扑异构酶-1失去耐受性的硬皮病患者肺部疾病的扩大。
Among the autoimmune rheumatic diseases, it is striking that autoantibodies targeting ubiquitously expressed proteins (eg, topoisomerase‐1) associate with specific clinical complications (eg, interstitial lung disease [ILD]). It has been proposed that enriched antigen expression in inflamed target tissue may play a role in focusing the autoimmune response. We sought to determine whether topoisomerase‐1 expression is enriched in lungs from patients with autoimmune/inflammatory diseases relative to normal lung. We used a 99‐core lung tissue microarray (TMA) containing lung tissue from 40 patients with autoimmune inflammatory ILD (cases) and 46 control subjects with normal lungs. We stained the TMA with antibodies to compare topoisomerase‐1 and CD8 expression between patients and control subjects and evaluated whether expression is enriched in specific cell types. Staining was analyzed, and statistical comparisons were performed. Cases were more likely to have global topoisomerase‐1 expression (53% vs 21%; P = 0.003), specifically in pneumocytes (47% vs 16%; P = 0.003) and stromal/immune cells (32% vs 5%; P = 0.002) compared with control subjects. CD8 cell density (223 cells/mm2 vs 102 cells/mm2; P = 0.018) was significantly higher in topoisomerase‐1–positive lung tissues compared with topoisomerase‐1–negative lung tissues. Interestingly, topoisomerase‐1 expression was significantly more common in scleroderma compared with normal lung (67% vs 21%; P = 0.036) and was present more frequently in pneumocytes in these patients (67% vs 16%; P = 0.018). Pulmonary expression of topoisomerase‐1 is increased in the setting of autoimmune ILD relative to normal lung, specifically in pneumocytes. This may contribute to the amplification of pulmonary disease in patients with scleroderma with a loss of tolerance to topoisomerase‐1.
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DOI：
10.1126/science.1246886
发表时间：
2014-01-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Joseph CG;Darrah E;Shah AA;Skora AD;Casciola-Rosen LA;Wigley FM;Boin F;Fava A;Thoburn C;Kinde I;Jiao Y;Papadopoulos N;Kinzler KW;Vogelstein B;Rosen A
通讯作者：
Rosen A
影响因子：
17.1
作者：
Konig MF;Abusleme L;Reinholdt J;Palmer RJ;Teles RP;Sampson K;Rosen A;Nigrovic PA;Sokolove J;Giles JT;Moutsopoulos NM;Andrade F
通讯作者：
Andrade F
影响因子：
6.9
作者：
Winstone, Tiffany A.;Hague, Cameron J.;Ryerson, Christopher J.
通讯作者：
Ryerson, Christopher J.
DOI：
10.1084/jem.20041367
发表时间：
2005-02-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Casciola-Rosen L;Nagaraju K;Plotz P;Wang K;Levine S;Gabrielson E;Corse A;Rosen A
通讯作者：
Rosen A
影响因子：
3.4
作者：
Hudson, Marie;Assayag, Deborah;Baron, Murray
通讯作者：
Baron, Murray