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Systemic Lupus Erythematosus Patients with DNASE1L3·Deficiency Have a Distinctive and Specific Genic Circular DNA Profile in Plasma
Cell-free (cf) extrachromosomal circular DNA (eccDNA) has a potential clinical application as a biomarker. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a complex immunological pathogenesis, associated with autoantibody synthesis. A previous study found that SLE patients w...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093232/ https://www.ncbi.nlm.nih.gov/pubmed/37048133 http://dx.doi.org/10.3390/cells12071061 |
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author | Gerovska, Daniela Araúzo-Bravo, Marcos J. |
author_facet | Gerovska, Daniela Araúzo-Bravo, Marcos J. |
author_sort | Gerovska, Daniela |
collection | PubMed |
description | Cell-free (cf) extrachromosomal circular DNA (eccDNA) has a potential clinical application as a biomarker. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a complex immunological pathogenesis, associated with autoantibody synthesis. A previous study found that SLE patients with deoxyribonuclease 1-like 3 (DNASE1L3) deficiency exhibit changes in the frequency of short and long eccDNA in plasma compared to controls. Here, using the DifCir method for differential analysis of short-read sequenced purified eccDNA data based on the split-read signal of the eccDNA on circulomics data, we show that SLE patients with DNASE1L3 deficiency have a distinctive profile of eccDNA excised by gene regions compared to controls. Moreover, this profile is specific; cf-eccDNA from the top 93 genes is detected in all SLE with DNASE1L3 deficiency samples, and none in the control plasma. The top protein coding gene producing eccDNA-carrying gene fragments is the transcription factor BARX2, which is involved in skeletal muscle morphogenesis and connective tissue development. The top gene ontology terms are ‘positive regulation of torc1 signaling’ and ‘chondrocyte development’. The top Harmonizome terms are ‘lymphopenia’, ‘metabolic syndrome x’, ‘asthma’, ‘cardiovascular system disease‘, ‘leukemia’, and ‘immune system disease’. Here, we show that gene associations of cf-eccDNA can serve as a biomarker in the autoimmune rheumatic diseases. |
format | Online Article Text |
id | pubmed-10093232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100932322023-04-13 Systemic Lupus Erythematosus Patients with DNASE1L3·Deficiency Have a Distinctive and Specific Genic Circular DNA Profile in Plasma Gerovska, Daniela Araúzo-Bravo, Marcos J. Cells Article Cell-free (cf) extrachromosomal circular DNA (eccDNA) has a potential clinical application as a biomarker. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a complex immunological pathogenesis, associated with autoantibody synthesis. A previous study found that SLE patients with deoxyribonuclease 1-like 3 (DNASE1L3) deficiency exhibit changes in the frequency of short and long eccDNA in plasma compared to controls. Here, using the DifCir method for differential analysis of short-read sequenced purified eccDNA data based on the split-read signal of the eccDNA on circulomics data, we show that SLE patients with DNASE1L3 deficiency have a distinctive profile of eccDNA excised by gene regions compared to controls. Moreover, this profile is specific; cf-eccDNA from the top 93 genes is detected in all SLE with DNASE1L3 deficiency samples, and none in the control plasma. The top protein coding gene producing eccDNA-carrying gene fragments is the transcription factor BARX2, which is involved in skeletal muscle morphogenesis and connective tissue development. The top gene ontology terms are ‘positive regulation of torc1 signaling’ and ‘chondrocyte development’. The top Harmonizome terms are ‘lymphopenia’, ‘metabolic syndrome x’, ‘asthma’, ‘cardiovascular system disease‘, ‘leukemia’, and ‘immune system disease’. Here, we show that gene associations of cf-eccDNA can serve as a biomarker in the autoimmune rheumatic diseases. MDPI 2023-03-31 /pmc/articles/PMC10093232/ /pubmed/37048133 http://dx.doi.org/10.3390/cells12071061 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gerovska, Daniela Araúzo-Bravo, Marcos J. Systemic Lupus Erythematosus Patients with DNASE1L3·Deficiency Have a Distinctive and Specific Genic Circular DNA Profile in Plasma |
title | Systemic Lupus Erythematosus Patients with DNASE1L3·Deficiency Have a Distinctive and Specific Genic Circular DNA Profile in Plasma |
title_full | Systemic Lupus Erythematosus Patients with DNASE1L3·Deficiency Have a Distinctive and Specific Genic Circular DNA Profile in Plasma |
title_fullStr | Systemic Lupus Erythematosus Patients with DNASE1L3·Deficiency Have a Distinctive and Specific Genic Circular DNA Profile in Plasma |
title_full_unstemmed | Systemic Lupus Erythematosus Patients with DNASE1L3·Deficiency Have a Distinctive and Specific Genic Circular DNA Profile in Plasma |
title_short | Systemic Lupus Erythematosus Patients with DNASE1L3·Deficiency Have a Distinctive and Specific Genic Circular DNA Profile in Plasma |
title_sort | systemic lupus erythematosus patients with dnase1l3·deficiency have a distinctive and specific genic circular dna profile in plasma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093232/ https://www.ncbi.nlm.nih.gov/pubmed/37048133 http://dx.doi.org/10.3390/cells12071061 |
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