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Expression of the Autoantigen Topoisomerase‐1 is Enriched in the Lung Tissues of Patients With Autoimmune Interstitial Lung Disease: A Case Control Study

BACKGROUND: 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 infla...

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Autores principales: Cottrell, Tricia R., Askin, Frederic, Halushka, Marc K., Casciola‐Rosen, Livia, McMahan, Zsuzsanna H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672300/
https://www.ncbi.nlm.nih.gov/pubmed/33118283
http://dx.doi.org/10.1002/acr2.11191
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author Cottrell, Tricia R.
Askin, Frederic
Halushka, Marc K.
Casciola‐Rosen, Livia
McMahan, Zsuzsanna H.
author_facet Cottrell, Tricia R.
Askin, Frederic
Halushka, Marc K.
Casciola‐Rosen, Livia
McMahan, Zsuzsanna H.
author_sort Cottrell, Tricia R.
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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/mm(2) vs 102 cells/mm(2); 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). CONCLUSIONS: 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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spelling pubmed-76723002020-11-23 Expression of the Autoantigen Topoisomerase‐1 is Enriched in the Lung Tissues of Patients With Autoimmune Interstitial Lung Disease: A Case Control Study Cottrell, Tricia R. Askin, Frederic Halushka, Marc K. Casciola‐Rosen, Livia McMahan, Zsuzsanna H. ACR Open Rheumatol Brief Report BACKGROUND: 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. METHODS: 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. RESULTS: 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/mm(2) vs 102 cells/mm(2); 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). CONCLUSIONS: 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. John Wiley and Sons Inc. 2020-10-29 /pmc/articles/PMC7672300/ /pubmed/33118283 http://dx.doi.org/10.1002/acr2.11191 Text en © 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Brief Report
Cottrell, Tricia R.
Askin, Frederic
Halushka, Marc K.
Casciola‐Rosen, Livia
McMahan, Zsuzsanna H.
Expression of the Autoantigen Topoisomerase‐1 is Enriched in the Lung Tissues of Patients With Autoimmune Interstitial Lung Disease: A Case Control Study
title Expression of the Autoantigen Topoisomerase‐1 is Enriched in the Lung Tissues of Patients With Autoimmune Interstitial Lung Disease: A Case Control Study
title_full Expression of the Autoantigen Topoisomerase‐1 is Enriched in the Lung Tissues of Patients With Autoimmune Interstitial Lung Disease: A Case Control Study
title_fullStr Expression of the Autoantigen Topoisomerase‐1 is Enriched in the Lung Tissues of Patients With Autoimmune Interstitial Lung Disease: A Case Control Study
title_full_unstemmed Expression of the Autoantigen Topoisomerase‐1 is Enriched in the Lung Tissues of Patients With Autoimmune Interstitial Lung Disease: A Case Control Study
title_short Expression of the Autoantigen Topoisomerase‐1 is Enriched in the Lung Tissues of Patients With Autoimmune Interstitial Lung Disease: A Case Control Study
title_sort expression of the autoantigen topoisomerase‐1 is enriched in the lung tissues of patients with autoimmune interstitial lung disease: a case control study
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672300/
https://www.ncbi.nlm.nih.gov/pubmed/33118283
http://dx.doi.org/10.1002/acr2.11191
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