International Journal of Molecular Sciences

Editorial

Jump to: Research, Review

3 pages, 178 KiB

Open AccessEditorial

From Pathogenesis to Treatment—New Perspectives in Rheumatology

by Elena Rezus and Catalin Codreanu

Int. J. Mol. Sci. 2023, 24(21), 15590; https://doi.org/10.3390/ijms242115590 - 26 Oct 2023

Viewed by 745

Abstract

Rheumatic diseases are characterized by complex pathogenic mechanisms, with intricate signaling pathways and various imbalances of proinflammatory and anti-inflammatory cytokines, especially in the case of immune-inflammatory conditions [...] Full article

(This article belongs to the Special Issue From Pathogenesis to Treatment—New Perspectives in Rheumatology)

Research

Jump to: Editorial, Review

14 pages, 890 KiB

Open AccessArticle

Inflammatory Biomarkers in the Diagnosis and Prognosis of Rheumatoid Arthritis–Associated Interstitial Lung Disease

by Natalia Mena-Vázquez, Francisco Javier Godoy-Navarrete, Jose Manuel Lisbona-Montañez, Rocío Redondo-Rodriguez, Sara Manrique-Arija, José Rioja, Arkaitz Mucientes, Patricia Ruiz-Limón, Aimara Garcia-Studer, Fernando Ortiz-Márquez, Begoña Oliver-Martos, Laura Cano-García and Antonio Fernández-Nebro

Int. J. Mol. Sci. 2023, 24(7), 6800; https://doi.org/10.3390/ijms24076800 - 5 Apr 2023

Cited by 10 | Viewed by 1903

Abstract

This study aimed to identify inflammatory factors and soluble cytokines that act as biomarkers in the diagnosis and prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We performed a nested prospective observational case–control study of patients with RA-ILD matched by sex, age, and [...] Read more.

This study aimed to identify inflammatory factors and soluble cytokines that act as biomarkers in the diagnosis and prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We performed a nested prospective observational case–control study of patients with RA-ILD matched by sex, age, and time since the diagnosis of RA. All participants underwent pulmonary function testing and high-resolution computed tomography. ILD was defined according to the criteria of the American Thoracic Society/European Respiratory Society; the progression of lung disease was defined as the worsening of FVC > 10% or DLCO > 15%. Inflammation-related variables included the inflammatory activity measured using the DAS28-ESR and a multiplex cytokine assay. Two Cox regression models were run to identify factors associated with ILD and the progression of ILD. The study population comprised 70 patients: 35 patients with RA-ILD (cases) and 35 RA patients without ILD (controls). A greater percentage of cases had higher DAS28-ESR (p = 0.032) and HAQ values (p = 0.003). The variables associated with RA-ILD in the Cox regression analysis were disease activity (DAS28) (HR [95% CI], 2.47 [1.17–5.22]; p = 0.017) and high levels of ACPA (HR [95% CI], 2.90 [1.24–6.78]; p = 0.014), IL-18 in pg/mL (HR [95% CI], 1.06 [1.00–1.12]; p = 0.044), MCP-1/CCL2 in pg/mL (HR [95% CI], 1.03 [1.00–1.06]; p = 0.049), and SDF-1 in pg/mL (HR [95% CI], 1.00 [1.00–1.00]; p = 0.010). The only variable associated with the progression of ILD was IL-18 in pg/mL (HR [95% CI], 1.25 [1.07–1.46]; p = 0.004). Our data support that the inflammatory activity was higher in patients with RA-ILD than RA patients without ILD. Some cytokines were associated with both diagnosis and poorer prognosis in patients with RA-ILD. Full article

(This article belongs to the Special Issue From Pathogenesis to Treatment—New Perspectives in Rheumatology)

► Show Figures

Figure 1

14 pages, 1063 KiB

Open AccessArticle

Fetuin-A: A Novel Biomarker of Bone Damage in Early Axial Spondyloarthritis. Results of an Interim Analysis of the SPACE Study

by Marta Favero, Francesca Ometto, Elisa Belluzzi, Giacomo Cozzi, Laura Scagnellato, Francesca Oliviero, Pietro Ruggieri, Andrea Doria, Mariagrazia Lorenzin and Roberta Ramonda

Int. J. Mol. Sci. 2023, 24(4), 3203; https://doi.org/10.3390/ijms24043203 - 6 Feb 2023

Cited by 2 | Viewed by 1544

Abstract

Our study aimed to evaluate the association between fetuin-A levels and the presence of radiographic sacroiliitis and syndesmophytes in patients with early axial spondyloarthritis (axSpA) and to identify potential predictors of radiographic damage in the sacroiliac joints (SIJs) after 24 months. Patients diagnosed [...] Read more.

Our study aimed to evaluate the association between fetuin-A levels and the presence of radiographic sacroiliitis and syndesmophytes in patients with early axial spondyloarthritis (axSpA) and to identify potential predictors of radiographic damage in the sacroiliac joints (SIJs) after 24 months. Patients diagnosed with axSpA in the Italian cohort of the SpondyloArthritis-Caught-Early (SPACE) study were included. Physical examinations, laboratory tests (including fetuin-A), SIJ,+ and spinal X-rays and MRIs at T0 (diagnosis) and at T24 were considered. Radiographic damage in the SIJs was defined according to the modified New York criteria (mNY). Fifty-seven patients were included in this analysis (41.2% male, median (interquartile range), chronic back pain [CBP] duration of 12 (8–18) months). Fetuin-A levels were significantly lower in patients with radiographic sacroiliitis compared to those without at T0 (207.9 (181.7–215.9) vs. 239.9 (217.9–286.9), respectively, p < 0.001) and at T24 (207.6 (182.5–246.5) vs. 261.1 (210.2–286.6) µg/mL, p = 0.03). At T0, fetuin-A levels were significantly higher in non-smokers, in patients with heel enthesitis and in those with a family history of axSpA; fetuin-A levels at T24 were higher in females, in patients with higher ESR or CRP at T0 and in those with radiographic sacroiliitis at T0. Fetuin-A levels at T0 were independently negatively associated with the likelihood of radiographic sacroiliitis (OR = 0.9 per 10-unit increase (95% CI 0.8, 0.999), p = 0.048); but not with the presence of syndesmophytes. After adjustment for confounders, fetuin-A levels at T0 and T24 were also negatively associated with mNY at T0 (β −0.5, p < 0.001) and at T24 (β −0.3, p < 0.001), respectively. Among other variables at T0, fetuin-A levels did not achieve statistical significance in predicting mNY at T24. Fetuin-A levels were negatively associated with radiographic damage of the SIJs, but not of the spine, in early axSpA and after 2 years of follow-up. Our findings suggest that fetuin-A levels may serve as a biomarker to identify patients with a higher risk of developing severe disease and early structural damage. Full article

(This article belongs to the Special Issue From Pathogenesis to Treatment—New Perspectives in Rheumatology)

► Show Figures

Figure 1

10 pages, 3092 KiB

Open AccessArticle

Lung Damage in Rheumatoid Arthritis—A Retrospective Study

by Georgiana Dinache, Claudiu Costinel Popescu, Corina Mogoșan, Luminita Enache, Mihaela Agache and Cătălin Codreanu

Int. J. Mol. Sci. 2023, 24(1), 28; https://doi.org/10.3390/ijms24010028 - 20 Dec 2022

Cited by 2 | Viewed by 2617

Abstract

The current study aimed to evaluate rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) in clinical practice and whether disease characteristics are associated with X-ray and high-resolution computed tomography (HR-CT) findings. Medical history of RA patients from a tertiary rheumatology clinic was [...] Read more.

The current study aimed to evaluate rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) in clinical practice and whether disease characteristics are associated with X-ray and high-resolution computed tomography (HR-CT) findings. Medical history of RA patients from a tertiary rheumatology clinic was retrieved from its electronic database starting from 1 January 2019 until the study date (8 August 2022) using International Classification of Disease version 10 codes for RA, ILD and exclusion criteria. The study included 78 RA patients (75.6% women, 15.4% active smokers), with average time from RA to ILD of 5.6 years. Regarding chest X-ray findings, men had a higher prevalence of nodules, combined fibrosis and nodules and combined bronchiectasis and nodules, rheumatoid factor (RF)-positive patients had a higher prevalence of fibrosis and anti-cyclic citrullinated peptide antibodies (ACPA)-positive patients had a higher prevalence of bronchiectasis. Regarding HR-CT findings, patients actively treated with methotrexate had a higher prevalence of nodules; a combination of fibrosis and nodules; combination of emphysema and nodules; and combination of fibrosis, emphysema and nodules. ILD develops within approximately 5 years from RA diagnosis, and ILD-associated imaging findings on chest X-rays and HR-CT are more prevalent among men with RA, among patients with positive RA serology (RF and/or ACPA) and RA patients on methotrexate. Full article

(This article belongs to the Special Issue From Pathogenesis to Treatment—New Perspectives in Rheumatology)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

9 pages, 290 KiB

Open AccessReview

Eosinophilic Fasciitis: Current and Remaining Challenges

by Diana Mazilu, Laura Alina Boltașiu (Tătaru), Denise-Ani Mardale, Maria Silviana Bijă, Sermina Ismail, Violeta Zanfir, Florentina Negoi and Andra Rodica Balanescu

Int. J. Mol. Sci. 2023, 24(3), 1982; https://doi.org/10.3390/ijms24031982 - 19 Jan 2023

Cited by 7 | Viewed by 3900

Abstract

Eosinophilic fasciitis (EF), defined as diffuse fasciitis with eosinophilia by Shulman in 1974, is a disease with unknown etiology and whose pathogenesis is still being researched. The diagnosis is based on the clinical aspects (skin induration with an “orange peel” appearance), the lab [...] Read more.

Eosinophilic fasciitis (EF), defined as diffuse fasciitis with eosinophilia by Shulman in 1974, is a disease with unknown etiology and whose pathogenesis is still being researched. The diagnosis is based on the clinical aspects (skin induration with an “orange peel” appearance), the lab results (eosinophilia, increased inflammatory markers), the skin biopsy with the pathognomonic histopathological result, as well as the typical MRI changes. The treatment includes glucocorticoids and immunosuppressive drugs. Due to severe refractory cases, the treatment remains a challenge. EF is still a disease with potential for further research. Full article

(This article belongs to the Special Issue From Pathogenesis to Treatment—New Perspectives in Rheumatology)

17 pages, 654 KiB

Open AccessReview

Arrhythmias and Conduction Disturbances in Patients with Systemic Sclerosis—A Systematic Literature Review

by Cristina Andreea Vrancianu, Ana Maria Gheorghiu, Dragos Emanuel Popa, Jeffrey Shi Kai Chan, Danish Iltaf Satti, Yan Hiu Athena Lee, Jeremy Man Ho Hui, Gary Tse, Ioan Ancuta, Ana Ciobanu and Mihai Bojinca

Int. J. Mol. Sci. 2022, 23(21), 12963; https://doi.org/10.3390/ijms232112963 - 26 Oct 2022

Cited by 6 | Viewed by 1947

Abstract

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and internal organ fibrosis and microvascular impairment, which can affect major organs, including the heart. Arrhythmias are responsible for approximately 6% of deaths in patients with SSc, and mainly occur due to myocardial [...] Read more.

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and internal organ fibrosis and microvascular impairment, which can affect major organs, including the heart. Arrhythmias are responsible for approximately 6% of deaths in patients with SSc, and mainly occur due to myocardial fibrosis, which causes electrical inhomogeneity. The aim of this study was to determine the frequency of arrhythmias and conduction disturbances in SSc cohorts, and to identify the characteristics and risk factors associated with the occurrence of dysrhythmias in patients with SSc. A systematic literature review using PubMed, Embase, Web of Science and Scopus databases was performed. Full-text articles in English with arrhythmias as the main topic published until 21 April 2022 were included. Most prevalent arrhythmias were premature supraventricular and ventricular contractions, while the most frequent conduction disturbance was represented by right bundle branch block (RBBB). Elevated concentrations of N-terminal prohormones of brain natriuretic peptides (NT-pro BNP) were associated with numerous types of atrial and ventricular arrhythmias, and with the occurrence of RBBB. A lower value of the turbulence slope (TS) emerged as an independent predictor for ventricular arrhythmias. In conclusion, dysrhythmias are frequent in SSc cohorts. Paraclinical and laboratory parameters are useful instruments that could lead to early diagnosis in the course of the disease. Full article

(This article belongs to the Special Issue From Pathogenesis to Treatment—New Perspectives in Rheumatology)

► Show Figures

Figure 1

26 pages, 2499 KiB

Open AccessReview

Adult-Onset Still’s Disease—A Complex Disease, a Challenging Treatment

by Luana Andreea Macovei, Alexandra Burlui, Ioana Bratoiu, Ciprian Rezus, Anca Cardoneanu, Patricia Richter, Andreea Szalontay and Elena Rezus

Int. J. Mol. Sci. 2022, 23(21), 12810; https://doi.org/10.3390/ijms232112810 - 24 Oct 2022

Cited by 12 | Viewed by 6134

Abstract

Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder with an unknown cause characterized by high-spiking fever, lymphadenopathy, hepatosplenomegaly, hyperferritinemia, and leukocytosis. The clinical course can be divided into three significant patterns, each with a different prognosis: Self-limited or monophasic, intermittent or polycyclic [...] Read more.

Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder with an unknown cause characterized by high-spiking fever, lymphadenopathy, hepatosplenomegaly, hyperferritinemia, and leukocytosis. The clinical course can be divided into three significant patterns, each with a different prognosis: Self-limited or monophasic, intermittent or polycyclic systemic, and chronic articular. Two criteria sets have been validated. The Yamaguchi criteria are the most generally used, although the Fautrel criteria offer the benefit of adding ferritin and glycosylated ferritin values. AOSD’s pathogenesis is not yet completely understood. Chemokines and pro-inflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor α (TNFα), interleukin (IL)-1, IL-6, IL-8, and IL-18, play a crucial role in the progression of illness, resulting in the development of innovative targeted therapeutics. There are no treatment guidelines for AOSD due to its rarity, absence of controlled research, and lack of a standard definition for remission and therapy objectives. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids (CS), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are used in AOSD treatment. Biological therapy, including IL-1, IL-6, IL-18, and IL-17 inhibitors, as well as TNFα or Janus-kinases (JAKs) inhibitors, is administered to patients who do not react to CS and csDMARDs or achieve an inadequate response. Full article

(This article belongs to the Special Issue From Pathogenesis to Treatment—New Perspectives in Rheumatology)

► Show Figures

Figure 1

28 pages, 433 KiB

Open AccessReview

The Involvement of Smooth Muscle, Striated Muscle, and the Myocardium in Scleroderma: A Review

by Ioana Bratoiu, Alexandra Maria Burlui, Anca Cardoneanu, Luana Andreea Macovei, Patricia Richter, Gabriela Rusu-Zota, Ciprian Rezus, Minerva Codruta Badescu, Andreea Szalontay and Elena Rezus

Int. J. Mol. Sci. 2022, 23(19), 12011; https://doi.org/10.3390/ijms231912011 - 9 Oct 2022

Cited by 4 | Viewed by 2339

Abstract

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by heterogeneous changes involving numerous organs and systems. The currently available data indicate that muscle injury (both smooth and striated muscles) is widespread and leads to significant morbidity, either directly or indirectly. From the [...] Read more.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by heterogeneous changes involving numerous organs and systems. The currently available data indicate that muscle injury (both smooth and striated muscles) is widespread and leads to significant morbidity, either directly or indirectly. From the consequences of smooth muscle involvement in the tunica media of blood vessels or at the level of the digestive tract, to skeletal myopathy (which may be interpreted strictly in the context of SSc, or as an overlap with idiopathic inflammatory myopathies), muscular injury in scleroderma translates to a number of notable clinical manifestations. Heart involvement in SSc is heterogenous depending on the definition used in the various studies. The majority of SSc patients experience a silent form of cardiac disease. The present review summarizes certain important features of myocardial, as well as smooth and skeletal muscle involvement in SSc. Further research is needed to fully describe and understand the pathogenic pathways and the implications of muscle involvement in scleroderma. Full article

(This article belongs to the Special Issue From Pathogenesis to Treatment—New Perspectives in Rheumatology)

13 pages, 776 KiB

Open AccessReview

Why Do We Need JAK Inhibitors in Systemic Lupus Erythematosus?

by Patricia Richter, Anca Cardoneanu, Alexandra Maria Burlui, Luana Andreea Macovei, Ioana Bratoiu, Oana Nicoleta Buliga-Finis and Elena Rezus

Int. J. Mol. Sci. 2022, 23(19), 11788; https://doi.org/10.3390/ijms231911788 - 4 Oct 2022

Cited by 13 | Viewed by 2773

Abstract

Systemic lupus erythematosus (SLE) is a chronic, multifactorial autoimmune disease with complex pathogenesis characterized by the imbalance of pro-inflammatory and anti-inflammatory cytokines. Janus kinases (JAKs), intracellular non-receptor tyrosine kinases, are essential for signal pathways of many cytokines. The JAK signal transducers and activators [...] Read more.

Systemic lupus erythematosus (SLE) is a chronic, multifactorial autoimmune disease with complex pathogenesis characterized by the imbalance of pro-inflammatory and anti-inflammatory cytokines. Janus kinases (JAKs), intracellular non-receptor tyrosine kinases, are essential for signal pathways of many cytokines. The JAK signal transducers and activators of transcription (STAT) pathways consist of four JAK kinases and seven STATs family members. The dysregulation of JAK-STAT pathways represents an important process in the pathogenesis of SLE. Thus, the use of therapies that target specific signaling pathways would be a challenge in SLE. It is well known that JAK inhibitors have real potential for the treatment of rheumatic diseases, but their efficacy in the treatment of SLE remains to be determined. JAK inhibitors are currently being investigated in phase II and III trials and are considered to become the next stage in SLE therapy. In this review, we report the current data regarding the efficacy of JAK inhibitors in SLE. The development of clinically useful kinase inhibitors might improve upon traditional therapeutic strategies. Full article

(This article belongs to the Special Issue From Pathogenesis to Treatment—New Perspectives in Rheumatology)

► Show Figures

Figure 1

Journal Menu

Journal Browser

From Pathogenesis to Treatment—New Perspectives in Rheumatology

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (9 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI