Rheumatic Disorder: From Basic Science to Clinical Practice

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20 October 2024

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20 December 2024

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Topic Information

Dear Colleagues,

Autoimmune rheumatic diseases (RDs) are chronic inflammatory diseases with a major health impact worldwide, but their management and classification are sometimes difficult due to unknown aetiology and heterogeneity in their clinical presentation. RDs have the largest and consistent impact across all ages of the population, and they affect a significant proportion of the population. Their economic and social burden results from a decreased quality of life, lost productivity, and increased costs of health care. Moreover, although RDs affect people of all ages, the demographic structure of the population indicates an increasing tendency towards an older population along with an increasing prevalence of these diseases. Therefore, improving our knowledge of RDs, from basic science to clinical practice, has become critical. The heterogeneity of RDs and the lack of any clear clinical correlation with pathology makes for inexact estimation of their incidence and prevalence. Moreover, more investigation is needed concerning the causes and mechanisms affecting the development and progression of these disorders, and moreover more studies are needed to discover innovative treatments. As a result, challenges in studying RDs lie in achieving accurate epidemiological data and making efforts to obtain significant progress in terms of etiological mechanisms, clinical behaviour and the genetic/epigenetic basis of the diseases, as well as early diagnosis, treatment, and management of patients.

Dr. Giulia Cassone
Dr. Caterina Vacchi
Dr. Andreina Manfredi
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	4.7	3.7	2013	15.4 Days	CHF 2600	Submit
Clinics and Practice clinpract	2.3	2.0	2011	26.4 Days	CHF 1600	Submit
Diagnostics diagnostics	3.6	3.6	2011	20.7 Days	CHF 2600	Submit
Journal of Clinical Medicine jcm	3.9	5.4	2012	17.9 Days	CHF 2600	Submit
Rheumato rheumato	-	-	2021	15.0 days *	CHF 1000	Submit

* Median value for all MDPI journals in the second half of 2023.

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Published Papers (7 papers)

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All Biomedicines Clinics and Practice Diagnostics JCM Rheumato

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12 pages, 1080 KiB  

Open AccessArticle

Specific Features of Juvenile Idiopathic Arthritis Patients’ Cytokine Profile

by Daria I. Kozlova, Arseny V. Rybakov, Karina A. Yureva, Vitaly V. Khizha, Lybov S. Sorokina, Mikhail M. Kostik and Alexandr B. Guslev

Biomedicines 2024, 12(1), 135; https://doi.org/10.3390/biomedicines12010135 - 09 Jan 2024

Viewed by 900

Abstract

Juvenile idiopathic arthritis (JIA) is a systemic autoimmune disease that affects the joints, leading to disability. Cytokines and signaling molecules expressed by the immune system cells play a key role in JIA pathogenesis. Understanding how their content changes during pathology development can open [...] Read more.

Juvenile idiopathic arthritis (JIA) is a systemic autoimmune disease that affects the joints, leading to disability. Cytokines and signaling molecules expressed by the immune system cells play a key role in JIA pathogenesis. Understanding how their content changes during pathology development can open up new opportunities for its diagnosis and treatment. The blood plasma of 30 patients with JIA (14 males and 16 females with a mean age of 12.2 ± 4.1) and 20 relatively healthy individuals (10 males and 10 females with a mean age of 10.20 ± 5.85) was analyzed to determine the levels of cytokines using the MILLIPLEX^® kit. An increase in interleukins (IL)-1α, 1β, 2, 4, 5, 6, 7, 8, 9, 10, 13, 15, 17F, 22, and 27 and a decrease in IL-3 levels have been shown in patients with JIA. Levels of cytokines, which are important for B-cell activation and proliferation, are increased, while levels of T-cell activating factors remained similar to the control group. Based on our results, it can be assumed that the use of combination therapy aimed at inhibiting both nonspecific interleukins and cytokines that activate B-cells will be more effective for the treatment of JIA. Full article

(This article belongs to the Topic Rheumatic Disorder: From Basic Science to Clinical Practice)

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12 pages, 1662 KiB  

Open AccessArticle

Correlation of Hematological Indices and Acute-Phase Reactants in Rheumatoid Arthritis Patients on Disease-Modifying Antirheumatic Drugs: A Retrospective Cohort Analysis

by Yu-Jen Pan, Kuei-Ying Su, Chih-Lung Shen and Yi-Feng Wu

J. Clin. Med. 2023, 12(24), 7611; https://doi.org/10.3390/jcm12247611 - 11 Dec 2023

Viewed by 797

Abstract

Acute-phase markers are often used to evaluate the disease activity of rheumatoid arthritis (RA). Occasionally, the serum levels of acute-phase reactants remain normal in patients with obvious inflamed joints. Hematological indices derived from complete blood counts have been shown to correlate with disease [...] Read more.

Acute-phase markers are often used to evaluate the disease activity of rheumatoid arthritis (RA). Occasionally, the serum levels of acute-phase reactants remain normal in patients with obvious inflamed joints. Hematological indices derived from complete blood counts have been shown to correlate with disease activity. This provides a potential practical implementation in daily practice. Only a few studies have evaluated the relation between hematological indices and novel RA treatment (i.e., biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); no research has examined the changes in hematological indices in RA treatments longitudinally. We conducted a retrospective study involving 273 RA patients with b/tsDMARD treatment and followed them for at least a year. Baseline, 3-month, and 6-month lab data were collected. The results indicated a reduction in the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) post-treatment. Higher baseline PLRs and SIIs were associated with a more significant reduction in ESR at three months (η² = 0.03/0.13, p = 0.21/0.023). NLR and SII correlated with CRP moderately at three months (r = 0.373/0.394, p < 0.001/< 0.001). A correlation comparison showed that the correlation of NLR and PLR with CRP differs during different periods (p = 0.037/0.004). Subgroup analysis revealed that the time effect on correlation is related to treatment with Janus kinase inhibitor and anti-interleukin-6 but not antitumor necrosis factors. Full article

(This article belongs to the Topic Rheumatic Disorder: From Basic Science to Clinical Practice)

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15 pages, 1882 KiB  

Open AccessArticle

Dissociating Autoantibody Responses against Ro52 Antigen in Patients with Anti-Synthetase or Anti-MDA5 Antibodies

by Akira Yoshida, Shunya Nagata, Yuka Okazaki, Hironari Hanaoka, Takahisa Gono and Masataka Kuwana

Diagnostics 2023, 13(24), 3621; https://doi.org/10.3390/diagnostics13243621 - 08 Dec 2023

Viewed by 1150

Abstract

We aimed to dissociate the autoantibody response against the Ro52 protein in patients with anti-synthetase or anti-melanoma differentiation-associated gene 5 (MDA5) antibodies to explore the potential roles of different anti-Ro52 autoantibody responses in disease subclassification. This study used a single-center, prospective myositis cohort [...] Read more.

We aimed to dissociate the autoantibody response against the Ro52 protein in patients with anti-synthetase or anti-melanoma differentiation-associated gene 5 (MDA5) antibodies to explore the potential roles of different anti-Ro52 autoantibody responses in disease subclassification. This study used a single-center, prospective myositis cohort involving 122 consecutive patients with anti-synthetase antibodies identified by RNA immunoprecipitation (RNA-IP) and 34 patients with anti-MDA5 antibodies detected using enzyme immunoassay (EIA). Anti-Ro52 antibodies were measured using commercial EIA kits, while anti-Ro/SSA antibodies were identified using RNA-IP. Clinical features and outcomes were stratified according to two different patterns of autoantibody responses against Ro52, including “isolated anti-Ro52”, defined by positive anti-Ro52 and negative anti-Ro/SSA antibodies, and “anti-SSA-Ro52”, defined by positive anti-Ro52 and anti-Ro/SSA antibodies. Isolated anti-Ro52 positivity was the most prevalent autoantibody response in patients with both anti-synthetase (40/122; 32.8%) and anti-MDA5 antibodies (8/34; 23.5%). Isolated anti-Ro52 or anti-SSA-Ro52 positivity was associated with Gottron’s sign in patients with anti-synthetase antibodies, while in patients with anti-MDA5 antibodies, isolated anti-Ro52 positivity was associated with respiratory insufficiency at initial presentation and poor overall survival. Isolated anti-Ro52 positivity could be a potential biomarker for patient stratification; however, the clinical significance of dissociating isolated anti-Ro52 positivity from overall anti-Ro52 positivity was not evident. Full article

(This article belongs to the Topic Rheumatic Disorder: From Basic Science to Clinical Practice)

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9 pages, 498 KiB  

Open AccessBrief Report

Fibrosing Progressive Interstitial Lung Disease in Rheumatoid Arthritis: A Multicentre Italian Study

by Marco Sebastiani, Vincenzo Venerito, Elenia Laurino, Stefano Gentileschi, Fabiola Atzeni, Claudia Canofari, Dario Andrisani, Giulia Cassone, Marlea Lavista, Francesco D’Alessandro, Caterina Vacchi, Arnaldo Scardapane, Bruno Frediani, Massimiliano Cazzato, Carlo Salvarani, Florenzo Iannone and Andreina Manfredi

J. Clin. Med. 2023, 12(22), 7041; https://doi.org/10.3390/jcm12227041 - 11 Nov 2023

Viewed by 886

Abstract

Background: The INBUILD study demonstrated the efficacy of nintedanib in the treatment of progressive fibrosing interstitial lung disease different to idiopathic pulmonary fibrosis, including rheumatoid arthritis (RA)-related ILD. Nevertheless, the prevalence of RA-ILD patients that may potentially benefit from nintedanib remains unknown. Objectives [...] Read more.

Background: The INBUILD study demonstrated the efficacy of nintedanib in the treatment of progressive fibrosing interstitial lung disease different to idiopathic pulmonary fibrosis, including rheumatoid arthritis (RA)-related ILD. Nevertheless, the prevalence of RA-ILD patients that may potentially benefit from nintedanib remains unknown. Objectives and methods: The aim of the present multicentre study was to investigate the prevalence and possible associated factors of fibrosing progressive patterns in a cross-sectional cohort of RA-ILD patients. Results: One hundred and thirty-four RA-ILD patients with a diagnosis of RA-ILD, who were confirmed at high-resolution computed tomography and with a follow-up of at least 24 months, were enrolled. The patients were defined as having a progressive fibrosing ILD in case of a relative decline in forced vital capacity > 10% predicted and/or an increased extent of fibrotic changes on chest imaging in a 24-month period. Respiratory symptoms were excluded to reduce possible bias due to the retrospective interpretation of cough and dyspnea. According to radiologic features, ILD was classified as usual interstitial pneumonia (UIP) in 50.7% of patients, nonspecific interstitial pneumonia in 19.4%, and other patterns in 29.8%. Globally, a fibrosing progressive pattern was recorded in 36.6% of patients (48.5% of patients with a fibrosing pattern) with a significant association to the UIP pattern. Conclusion: We observed that more than a third of RA-ILD patients showed a fibrosing progressive pattern and might benefit from antifibrotic treatment. This study shows some limitations, such as the retrospective design. The exclusion of respiratory symptoms’ evaluation might underestimate the prevalence of progressive lung disease but increases the value of results. Full article

(This article belongs to the Topic Rheumatic Disorder: From Basic Science to Clinical Practice)

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7 pages, 233 KiB  

Open AccessBrief Report

The Influence of Time on the Epidemiology and Clinical Manifestations of Behçet’s Disease in Brazil

by Lilian T. Hirata, Carlos Eduardo G. Teixeira, Eduardo P. Magalhaes, Ana Paula T. Del Rio, Ibsen Bellini Coimbra and Zoraida Sachetto

J. Clin. Med. 2023, 12(22), 7008; https://doi.org/10.3390/jcm12227008 - 09 Nov 2023

Viewed by 577

Abstract

Objective: Modifications in the severity and clinical expression of Behçet’s disease (BD) have been described in some areas that are considered endemic for the disease. This study aims to evaluate the chronological changes in epidemiology and clinical characteristics of BD patients in a [...] Read more.

Objective: Modifications in the severity and clinical expression of Behçet’s disease (BD) have been described in some areas that are considered endemic for the disease. This study aims to evaluate the chronological changes in epidemiology and clinical characteristics of BD patients in a referral center in Brazil, which is considered a non-endemic area for the disease. Methods: A descriptive and cross-sectional study involving BD patients divided into two groups: group 1 patients were diagnosed and followed between 1988 and 2010, and group 2 were diagnosed and followed between 2011 and 2022. Results: No significant differences were found regarding gender and age at onset of symptoms between groups. We found a significant decrease in the frequency of bilateral ocular involvement, posterior uveitis, and retinal vasculitis. Conclusion: The demographic dates of this group of Brazilian BD patients remained similar over the last decade. Our study supports the notion that BD is becoming lighter in some regions. BD is a severe blinding disorder, and we found a lower frequency of ocular involvement over time. These findings may be attributed to a higher level of education of patients and a growing awareness of the disease. Newer immunomodulating and biologic agents may offer an improved prognosis in patients with BD with severe manifestations. Full article

(This article belongs to the Topic Rheumatic Disorder: From Basic Science to Clinical Practice)

17 pages, 1416 KiB  

Open AccessArticle

Infection Risk, Mortality, and Hypogammaglobulinemia Prevalence and Associated Factors in Adults Treated with Rituximab: A Tertiary Care Center Experience

by Moustafa S. Alhamadh, Thamer S. Alhowaish, Alaa Mathkour, Bayan Altamimi, Shahd Alheijani and Abdulrahman Alrashid

Clin. Pract. 2023, 13(6), 1286-1302; https://doi.org/10.3390/clinpract13060115 - 25 Oct 2023

Cited by 1 | Viewed by 1311

Abstract

Background: Rituximab is a human monoclonal antibody directed against the B-cell transmembrane protein CD20. Although well-tolerated, given its mechanism of action, rituximab can induce a state of severe immunosuppression, increasing the risk of opportunistic and fulminant infection and mortality. Aim: To evaluate the [...] Read more.

Background: Rituximab is a human monoclonal antibody directed against the B-cell transmembrane protein CD20. Although well-tolerated, given its mechanism of action, rituximab can induce a state of severe immunosuppression, increasing the risk of opportunistic and fulminant infection and mortality. Aim: To evaluate the risk of infection, mortality, and hypogammaglobulinemia and their associated factors among rituximab receivers. Method: This was a single-center retrospective cohort study of adults treated with rituximab for various indications. Hypogammaglobulinemia was defined by a cut-off value below the normal limit (an IgG level of <7.51 g/L, an IgM level of <0.46 g/L, and/or an IgA level of <0.82 g/L). Patients who met the definition of hypogammaglobinemia solely based on IgA were excluded. Severe infection was defined as any infection that required intensive care unit admission. Results: A total of 137 adults with a mean age of 47.69 ± 18.86 years and an average BMI of 28.57 ± 6.55 kg/m² were included. Hematological malignancies and connective tissue diseases were the most common primary diagnoses for which rituximab was used. More than half of the patients received the 375 mg/m² dose. Rituximab’s mean cumulative dose was 3216 ± 2282 mg, and the overall mortality rate was 22.6%. Hypogammaglobulinemia was diagnosed in 43.8% of the patients, and it was significantly more prevalent among males and the 375 mg/m² and 500 mg doses. Hematological malignancy was the only predictor for infection. Patients with blood type AB or B, hematological malignancies, and corticosteroids had a significantly higher mortality rate. Receiving the 1000 mg dose and having a low CD19 were associated with a significantly lower risk of infection and mortality, respectively. Conclusions: Hypogammaglobulinemia was diagnosed in 43.8% of the patients, and it was significantly more common among males and the 375 mg/m² and 500 mg doses. Hematological malignancies were significantly associated with higher infection and mortality rates, while corticosteroids were significantly associated with a higher mortality. Since the culprit of mortality was infection, these findings highlight the critical need for more frequent immunological monitoring during rituximab treatment period to mitigate the burden of infection and identify candidates for immunoglobulin replacement. Full article

(This article belongs to the Topic Rheumatic Disorder: From Basic Science to Clinical Practice)

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13 pages, 311 KiB  

Open AccessArticle

Mean Platelet Volume in a Series of 315 Patients with Rheumatoid Arthritis: Relationship with Disease Characteristics, including Subclinical Atherosclerosis and Cardiovascular Comorbidity

by Marta González-Sierra, Alejandro Romo-Cordero, Juan Carlos Quevedo-Abeledo, Adrián Quevedo-Rodríguez, Fuensanta Gómez-Bernal, Antonia de Vera-González, Raquel López-Mejías, Candelaria Martín-González, Miguel Ángel González-Gay and Iván Ferraz-Amaro

Diagnostics 2023, 13(20), 3208; https://doi.org/10.3390/diagnostics13203208 - 14 Oct 2023

Cited by 1 | Viewed by 1213

Abstract

Mean platelet volume (MPV) refers to the average platelet size in femtoliters. Increased or decreased MPV has been associated with several disorders, including inflammatory and cardiovascular diseases. In the present study, our objective was to analyze the relationship of MPV with disease activity [...] Read more.

Mean platelet volume (MPV) refers to the average platelet size in femtoliters. Increased or decreased MPV has been associated with several disorders, including inflammatory and cardiovascular diseases. In the present study, our objective was to analyze the relationship of MPV with disease activity in a large and well-characterized series of patients with rheumatoid arthritis (RA). This is a cross-sectional study that included 315 patients with RA and 208 controls matched by sex and age. Complete blood count, including MPV, was assessed. Multivariable analysis was performed to examine the relationship of MPV with RA disease characteristics, carotid atherosclerosis, and traditional cardiovascular factors, including a comprehensive profile of lipid molecules and insulin resistance or beta cell function indices. The multivariable analysis, which includes other hematological modifications produced by the disease and platelet values, showed that MPV levels were significantly lower in RA patients than in controls. Erythrocyte sedimentation rate and interleukin-6, but not C-reactive protein, were negatively correlated with MPV after adjustment for covariates. Similarly, disease activity and MPV had a significant and independent negative correlation. No relationships were found between MPV and cardiovascular risk factors, lipid profile or insulin resistance indices or subclinical atherosclerosis. In conclusion, patients with RA have lower levels of MPV than controls. MPV is negatively related to acute phase reactants and disease activity in RA. Full article

(This article belongs to the Topic Rheumatic Disorder: From Basic Science to Clinical Practice)

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