The Importance of Diagnosing and Predicting Rheumatic Diseases: Biomarkers, Indexes and Tools

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 5135

Special Issue Editors


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Guest Editor
1. Rheumatology Department, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain
2. Fisiología Vegetal Departamento Ciencias Farmacéuticas y de la Salud Facultad de Farmacia Universidad San Pablo‐CEU Universities Boadilla del Monte, 28668 Madrid, Spain
Interests: Prediction and Prognosis biomarkers; bioinformatics; GWAS; epiGWAS; SNPs; severity scores

E-Mail Website
Guest Editor
1. Rheumatology Department, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain
2. Chair UAM-ROCHE, EPID-Future, Universidad Autónoma de Madrid (UAM), 28034 Madrid, Spain
Interests: rheumatoid arthritis; psoriatic arthritis; vasculitis; comorbidities

Special Issue Information

Dear Colleagues,

Rheumatoid arthritis (RA) is a common systemic autoimmune disease with a prevalence of around 1% in the general population. Although the aetiopathogenesis of RA has not been fully elucidated, it is considered a complex disease in which the interaction between genetic, environmental and stochastic factors leads to a chronic infiltration of the synovial membrane by a variety of cells of the immune system, and, finally, radiographic progression and joint destruction.

During the last few years, solid evidence has confirmed the usefulness of early therapeutic intervention in the “window of opportunity”, with T2T strategies focused on achieving sustained remission, or at least low disease activity, leading to better outcomes. In order to offer patients tailored therapy to improve efficacy and reduce side effects, reliable and efficient prediction and prognosis biomarkers are needed, as well as severity indices. Along these lines, attempts have been made to generate predictive models that combine different biomarkers, although many environmental, molecular, genetic and epigenetic factors involved in the disease remain to be investigated. Additionally, the application of novel tools such as artificial intelligence or machine learning techniques could be useful to predict the response and safety of drugs used for the treatment of RA.

Finally, it should be noted that cardiovascular and pulmonary combabilities now constitute the main causes of mortality in RA. In this sense, the biomarkers under development to predict patients who are at risk of developing these comorbidities are of special interest, with the aim of anticipating their diagnosis and establishing early treatment. This Special Issue attempts to review the best predictive models of the evolution of the disease and provide tools to help the physician to make decisions about the best treatment for the patient.In this Special Issue, we will also address the importance of some biomarkers for the early detection of the main comorbidities associated with RA.

Dr. Nuria Montes
Dr. Santos Castaneda
Guest Editors

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Keywords

  • prediction and prognosis biomarkers
  • bioinformatics
  • GWAS
  • epiGWAS
  • SNPs
  • severity scores
  • combabilities
  • cardiovascular and pulmonary combabilities
  • predictive models

Published Papers (3 papers)

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Research

15 pages, 1286 KiB  
Article
Relationship of Blood Inflammatory Composite Markers with Cardiovascular Risk Factors and Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis
by Marta González-Sierra, Adrián Quevedo-Rodríguez, Alejandro Romo-Cordero, Gaël González-Chretien, Juan Carlos Quevedo-Abeledo, Antonia de Vera-González, Alejandra González-Delgado, Candelaria Martín-González, Miguel Ángel González-Gay and Iván Ferraz-Amaro
Life 2023, 13(7), 1469; https://doi.org/10.3390/life13071469 - 28 Jun 2023
Cited by 3 | Viewed by 1204
Abstract
The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIRI, neutrophils × monocytes/lymphocytes) have been described as potential blood-derived inflammatory biomarkers in several diseases. Rheumatoid arthritis is an inflammatory disease that has been related to an increased risk [...] Read more.
The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIRI, neutrophils × monocytes/lymphocytes) have been described as potential blood-derived inflammatory biomarkers in several diseases. Rheumatoid arthritis is an inflammatory disease that has been related to an increased risk of cardiovascular (CV) disease. In the present work, we analyze how these hematological composite scores of inflammation are related to classic CV risk factors and subclinical atherosclerosis in patients with RA. In this cross-sectional study that included 430 patients with RA, the NLR, MLR, PLR, and SIRI scores were calculated. Multivariable analysis was performed to examine the relationships of these composite blood scores with subclinical carotid atherosclerosis and with traditional cardiovascular factors, producing a complete profile of lipid molecules and insulin resistance or indices of beta-cell function, and a Systematic Coronary Risk Assessment (SCORE2) calculation. C-reactive protein and disease activity were significantly and positively associated with the four blood composite scores. SCORE2 was significantly associated with higher values of SIRI, NLR, and MLR, but not PLR. These relationships were maintained when SCORE 2 was considered categorical; patients in the very high CV risk category had higher values in all hematological composite scores, except PLR. In the multivariable analysis, SIRI and NLR were independently associated with higher levels of beta cell dysfunction. In conclusion, SCORE2 and the values of the hematological composite scores were positively correlated in patients with RA. In addition, there were some relationships of these scores with traditional CV risk factors, with their association with beta cell dysfunction being the most consistent. Full article
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18 pages, 2751 KiB  
Article
Determination of Heterogeneous Proteomic and Metabolomic Response in anti-TNF and anti-IL-6 Treatment of Patients with Rheumatoid Arthritis
by Alexander A. Stepanov, Kristina A. Malsagova, Arthur T. Kopylov, Vladimir R. Rudnev, Dmitry E. Karateev, Evgenia I. Markelova, Elena L. Luchikhina, Elena E. Borisova and Anna L. Kaysheva
Life 2023, 13(2), 596; https://doi.org/10.3390/life13020596 - 20 Feb 2023
Cited by 2 | Viewed by 1653
Abstract
Reduction in tumor necrosis factor (αTNF) and interleukin-6 (IL-6) activities is a widely utilized strategy for the treatment of rheumatoid arthritis (RA) with a high success rate. Despite both schemes targeting the deprivation of inflammatory reactions caused by the excessive activity of cytokines, [...] Read more.
Reduction in tumor necrosis factor (αTNF) and interleukin-6 (IL-6) activities is a widely utilized strategy for the treatment of rheumatoid arthritis (RA) with a high success rate. Despite both schemes targeting the deprivation of inflammatory reactions caused by the excessive activity of cytokines, their mechanisms of action and the final output are still unequal. This was a comparative longitudinal study that lasted for 24 weeks and aimed to find the answer to why the two schemes of therapy can pass out of proportion in attitude of their efficiency. What are the differences in metabolic and proteomic responses among patients who were being treated by either the anti-TNF or anti-IL-6 strategy? We found increased levels of immunoglobulins A and G (more than 2-fold in anti-IL-6 and more than 4-5-fold in anti-TNF groups) at the final stage (24 weeks) of monitoring but the most profound increase was determined for µ-chains of immunoglobulins in both groups of study. Metabolomic changes displayed main alterations with regard to arginine metabolism and collagen maintenance, where arginine increased 8.86-fold (p < 0.001) in anti-TNF and 5.71-fold (p < 0.05) in anti-IL-6 groups but patients treated by the anti-TNF scheme suffered a higher depletion of arginine before the start of therapy. Some indicators of matrix and bone tissue degradation also increased 4-hydroxyproline (4-HP) more than 6-fold (p < 0.001) in anti-TNF and more than 2-fold (p < 0.05) in the anti-IL-6 group, but the growth dynamics in the anti-IL6 group was delayed (gradually raised at week 24) compared to the anti-TNF group (raised at week 12) following a smooth reduction. The ELISA analysis of IL-6 and TNFα concentration in the study population supported proteomic and metabolomic data. A positive correlation between ΔCDAI and ΔDAS28 indicators and ESR and CRP was established for the majority of patients after 24 weeks of treatment where ESR and CRP reduced by 20% and 40% finally, respectively. A regression model using the Forest Plot was estimated to elucidate the impact of the most significant clinical, biochemical, and anthropometric indicators for the evaluation of differences between considered anti-TNF and anti-IL-6 schemes of therapy. Full article
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10 pages, 2123 KiB  
Article
Disease Activity Is More Associated with IL-1 Than with IL-6 in Patients with Rheumatoid Arthritis
by Cristina Almeida-Santiago, Juan Carlos Quevedo-Abeledo, María Vanesa Hernández-Hernández, Antonia de Vera-González, Alejandra González-Delgado, Miguel Ángel González-Gay and Iván Ferraz-Amaro
Life 2023, 13(1), 82; https://doi.org/10.3390/life13010082 - 28 Dec 2022
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Abstract
Interleukin-1 receptor antagonist (IL-1ra) concentration reflects and is proportional to IL-1 production. Both IL-1 and IL-6 are involved in the pathogenesis of rheumatoid arthritis (RA). However, the relationship of serum levels of these two cytokines to each other in RA patients is not [...] Read more.
Interleukin-1 receptor antagonist (IL-1ra) concentration reflects and is proportional to IL-1 production. Both IL-1 and IL-6 are involved in the pathogenesis of rheumatoid arthritis (RA). However, the relationship of serum levels of these two cytokines to each other in RA patients is not well-understood. In this study, our objective was to analyze the possible linear correlation between IL-1ra and IL-6 in patients with RA, and how both are related to the inflammatory activity of the disease. IL-6 and IL-1ra levels were measured in 407 patients with RA. Linear regression and partial correlations were conducted to analyze the relationship between both cytokines, and their association with RA characteristics. No correlation was found between serum levels of IL-6 and IL-1ra (Pearson’s r 0.031, p = 0.61). However, disease activity and acute phase reactants were positively and significantly associated with both cytokines. Nevertheless, after controlling for covariates, disease activity scores were more strongly associated with IL-1ra compared to IL-6. Circulating IL-6 and IL-1ra do not correlate with each other in RA patients. Although both are associated with disease activity and acute phase reactants, the relationship of disease activity to IL-1ra is greater than that to IL-6. Full article
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