Circulating levels of PADs and citrullinated histone H3 in SARS-CoV-2 infection: Influence of genetic polymorphisms

IF 2.9 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Clinica Chimica Acta Pub Date : 2025-03-01 Epub Date: 2025-02-02 DOI:10.1016/j.cca.2025.120180
Ilse Adriana Gutiérrez-Pérez , Gloria Pérez-Rubio , José Rafael Villafan-Bernal , Ivette Buendía-Roldán , Oscar Zaragoza-García , Leslie Chávez-Galán , Pedro Rosendo-Chalma , Ingrid Fricke-Galindo , Ramcés Falfán-Valencia , Iris Paola Guzmán-Guzmán
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Abstract

Background

Peptidyl arginine deiminases (PADs) and citrullinated H3 histone (H3Cit) play a crucial role in the inflammatory response. These components determine various clinical situations in COVID-2019 associated pneumonia. Single nucleotide polymorphisms (SNPs) in the genes PADI2 and PADI4 may influence the outcome of poorer patient outcomes. We analyze the association of circulating levels NETs biomarkers (PAD2, PAD4, and H3Cit) and the SNPs on PADI2 (rs1005753 and rs2235926) and PADI4 (rs11203366, rs11203367, and rs874881) in hospitalized patients with severe acute respiratory distress syndrome (ARDs) by SARS-CoV-2 pneumonia.

Methods

A cross-sectional study in 160 hospitalized patients with ARDs by SARS-CoV-2 pneumonia. The plasma levels of PAD2, PAD4, and H3Cit were determined by ELISA method. The SNPs were determined by qPCR using TaqMan probes. Logistic regression models and receiver operating characteristics (ROC) curve were used to assess the association and predictive value of PAD2, PAD4, and H3Cit plasma levels in outcome by ARDs by SARS-CoV-2 pneumonia.

Results

PAD2, PAD4, and H3Cit concentrations were predictors of invasive mechanical ventilation (IMV) requirement and non-survival. PAD2 were associated with non-survival, while PAD4 and H3Cit were associated with requirement IMV. In addition, PAD2 and PAD4 concentrations were related with inflammation markers such as NLR, MLR, dNLR, SII, SIRI, AISI, and NHL. In the carriers of TT genotype of rs1005753 of PADI2 were associated with increased of H3Cit, while, the carriers of GTG/GTG haplotype of PADI4 was related to the presence of increased of PAD4 circulating levels.

Conclusion

SNPs in PADI2 and PADI4 have a significant influence on concentrations of PAD2, PAD4, and H3Cit, which are predictor markers of requirement IMV and non-survival in severe ARDS by SARS-CoV-2 pneumonia.
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SARS-CoV-2感染中pad和瓜氨酸化组蛋白H3的循环水平:遗传多态性的影响
背景:肽基精氨酸脱亚胺酶(PADs)和瓜氨酸化H3组蛋白(H3Cit)在炎症反应中起重要作用。这些组成部分决定了2019冠状病毒相关肺炎的各种临床情况。PADI2和PADI4基因的单核苷酸多态性(snp)可能影响较差患者预后的结果。我们分析了SARS-CoV-2肺炎合并严重急性呼吸窘迫综合征(ARDs)住院患者循环水平NETs生物标志物(PAD2、PAD4和H3Cit)与PADI2 (rs1005753和rs2235926)和PADI4 (rs11203366、rs11203367和rs874881) snp的相关性。方法:对160例SARS-CoV-2肺炎合并急性呼吸窘迫综合征住院患者进行横断面研究。采用ELISA法检测血浆中PAD2、PAD4、H3Cit水平。采用TaqMan探针进行qPCR检测。采用Logistic回归模型和受试者工作特征(ROC)曲线评价血浆PAD2、PAD4和H3Cit水平与SARS-CoV-2肺炎致ARDs结局的相关性及预测价值。结果:PAD2、PAD4和H3Cit浓度是有创机械通气(IMV)需求和非生存期的预测因子。PAD2与无生存相关,而PAD4和H3Cit与所需IMV相关。此外,PAD2和PAD4浓度与NLR、MLR、dNLR、SII、SIRI、AISI和NHL等炎症标志物相关。TT基因型rs1005753 PADI2携带者与H3Cit升高相关,而GTG/GTG单倍型PADI4携带者与PAD4循环水平升高相关。结论:PADI2和PADI4 snp对SARS-CoV-2肺炎所致严重急性呼吸窘迫综合征(ARDS)患者血清PAD2、PAD4和H3Cit浓度有显著影响。
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来源期刊
Clinica Chimica Acta
Clinica Chimica Acta 医学-医学实验技术
CiteScore
10.10
自引率
2.00%
发文量
1268
审稿时长
23 days
期刊介绍: The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.
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