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Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis

Protein citrullination is carried out by peptidylarginine deiminase type 4 (PAD4) enzyme. As a consequence of this process, post-translationally modified proteins are formed that become antigens for anti-citrullinated protein antibodies (ACPA). The study aimed at identifying whether the PADI4 gene i...

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Autores principales: Kolarz, Bogdan, Ciesla, Marek, Dryglewska, Magdalena, Majdan, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408948/
https://www.ncbi.nlm.nih.gov/pubmed/32629762
http://dx.doi.org/10.3390/jcm9072049
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author Kolarz, Bogdan
Ciesla, Marek
Dryglewska, Magdalena
Majdan, Maria
author_facet Kolarz, Bogdan
Ciesla, Marek
Dryglewska, Magdalena
Majdan, Maria
author_sort Kolarz, Bogdan
collection PubMed
description Protein citrullination is carried out by peptidylarginine deiminase type 4 (PAD4) enzyme. As a consequence of this process, post-translationally modified proteins are formed that become antigens for anti-citrullinated protein antibodies (ACPA). The study aimed at identifying whether the PADI4 gene is subject to epigenetic regulation through methylation of its promoter region, whether the degree of methylation differs in healthy individuals vs. rheumatoid arthritis (RA) patients and changes in correlation with ACPA, anti-PAD4 and disease activity. A total of 125 RA patients and 30 healthy controls were enrolled. Quantitative real-time methylation-specific PCR was used to analyze the methylation status. ACPA and anti-PAD4 antibodies were determined in serum by enzyme-linked immunosorbent immunoassay. The differences were observed in the degree of PADI4 gene promoter methylation between RA patients and HC, along with an upward trend for the methylation in RA, which was inversely proportional to the disease activity. A weak or modest negative correlation between the degree of PADI4 gene methylation and anti-PAD4, disease activity score (DAS28) and ACPA level has been found. The elevated methylation is associated with lower disease activity, lower levels of ACPA and aPAD4. The methylation degree in this area is growing up during effective treatment and might play a role in the RA pathophysiology and therefore could be a future therapeutic target.
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spelling pubmed-74089482020-08-13 Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis Kolarz, Bogdan Ciesla, Marek Dryglewska, Magdalena Majdan, Maria J Clin Med Article Protein citrullination is carried out by peptidylarginine deiminase type 4 (PAD4) enzyme. As a consequence of this process, post-translationally modified proteins are formed that become antigens for anti-citrullinated protein antibodies (ACPA). The study aimed at identifying whether the PADI4 gene is subject to epigenetic regulation through methylation of its promoter region, whether the degree of methylation differs in healthy individuals vs. rheumatoid arthritis (RA) patients and changes in correlation with ACPA, anti-PAD4 and disease activity. A total of 125 RA patients and 30 healthy controls were enrolled. Quantitative real-time methylation-specific PCR was used to analyze the methylation status. ACPA and anti-PAD4 antibodies were determined in serum by enzyme-linked immunosorbent immunoassay. The differences were observed in the degree of PADI4 gene promoter methylation between RA patients and HC, along with an upward trend for the methylation in RA, which was inversely proportional to the disease activity. A weak or modest negative correlation between the degree of PADI4 gene methylation and anti-PAD4, disease activity score (DAS28) and ACPA level has been found. The elevated methylation is associated with lower disease activity, lower levels of ACPA and aPAD4. The methylation degree in this area is growing up during effective treatment and might play a role in the RA pathophysiology and therefore could be a future therapeutic target. MDPI 2020-06-30 /pmc/articles/PMC7408948/ /pubmed/32629762 http://dx.doi.org/10.3390/jcm9072049 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kolarz, Bogdan
Ciesla, Marek
Dryglewska, Magdalena
Majdan, Maria
Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis
title Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis
title_full Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis
title_fullStr Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis
title_full_unstemmed Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis
title_short Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis
title_sort peptidyl arginine deiminase type 4 gene promoter hypo-methylation in rheumatoid arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408948/
https://www.ncbi.nlm.nih.gov/pubmed/32629762
http://dx.doi.org/10.3390/jcm9072049
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