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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...

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Autores principales: Gerovska, Daniela, Araúzo-Bravo, Marcos J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
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.
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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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