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Search Results (259)

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Keywords = early rheumatoid arthritis

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13 pages, 1542 KiB  
Case Report
Reclassification of Seronegative Rheumatoid Arthritis as Anti-PL-12 Antisynthetase Syndrome with Interstitial Lung Disease and Joint Involvement–Case Report
by Diana Elena Cosău, Alexandru Dan Costache, Irina Iuliana Costache Enache, Ionela Lăcrămioara Șerban, Luiza Andreea Petrariu, Cristina Pomîrleanu, Mara Russu, Vladia Lăpuște and Codrina Ancuța
Reports 2025, 8(3), 123; https://doi.org/10.3390/reports8030123 - 26 Jul 2025
Viewed by 372
Abstract
Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include [...] Read more.
Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include Raynaud’s phenomenon and “mechanic’s hands”. Among antisynthetase antibodies, anti-PL-12 is notably associated with predominant or isolated ILD and may occur in the absence of clinically evident myositis, thereby complicating timely diagnosis. Case Presentation: We are presenting a 45-year-old non-smoking female patient with a prior diagnosis of seronegative rheumatoid arthritis (RA) who developed progressive dyspnea, dry cough, and sicca symptoms. High-resolution computed tomography revealed a nonspecific interstitial pneumonia (NSIP) pattern. Despite normal creatine kinase and lactate dehydrogenase levels, serological work-up revealed positive anti-PL-12 and anti-Ro52 antibodies, supporting a diagnosis of antisynthetase syndrome without myositis, fulfilling the diagnostic criteria for ASyS per Connors and Solomon. Treatment with corticosteroids and cyclophosphamide induced clinical and functional respiratory improvement, while azathioprine was initiated for maintenance. Conclusions: This case underscores the clinical heterogeneity of antisynthetase syndrome and highlights the diagnostic challenge posed by anti-PL-12–associated ILD in the absence of myositis. Importantly, it demonstrates that in patients with pre-existing rheumatologic diagnoses, the emergence of atypical pulmonary manifestations warrants repeat serologic evaluation to assess ASyS and other autoimmune conditions. Early diagnosis and immunosuppressive treatment are essential to optimize outcomes. Full article
(This article belongs to the Section Critical Care/Emergency Medicine/Pulmonary)
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13 pages, 951 KiB  
Article
Corticosteroids and Vertebral Trabecular Bone Quality in Women with Rheumatoid Arthritis
by Jose Jorge Gomez-Camarena, Melissa Ramirez-Villafaña, Eli Efrain Gomez-Ramirez, Fabiola Gonzalez-Ponce, Miriam Fabiola Alcaraz-Lopez, Juan Manuel Ponce-Guarneros, Maria Luisa Vazquez-Villegas, Larissa Renne Rodriguez-Santillan, Norma Alejandra Rodriguez-Jimenez, Ana Miriam Saldaña-Cruz, Ernesto German Cardona-Muñoz, Sylvia Elena Totsuka-Sutto, Jorge Ivan Gamez-Nava and Laura Gonzalez-Lopez
J. Clin. Med. 2025, 14(15), 5223; https://doi.org/10.3390/jcm14155223 - 23 Jul 2025
Viewed by 338
Abstract
Background/Objectives: Glucocorticoids (GCs) are frequently prescribed to control disease in Rheumatoid Arthritis (RA). However, long-term GC therapy with high daily doses is associated with bone involvement, which is considered the main extra-articular complication of RA. The trabecular bone score (TBS) has proven useful [...] Read more.
Background/Objectives: Glucocorticoids (GCs) are frequently prescribed to control disease in Rheumatoid Arthritis (RA). However, long-term GC therapy with high daily doses is associated with bone involvement, which is considered the main extra-articular complication of RA. The trabecular bone score (TBS) has proven useful in assessing vertebral trabecular bone quality and fracture risk. To identify whether the long-term treatment of low doses of GCs are associated with low vertebral TBS in RA patients. Methods: A cross-sectional study, including 203 women with RA (ACR, 1987). Clinical, epidemiologic, and therapeutic variables were assessed. We identified the current daily dose, duration, and cumulative dose of GCs. Vertebral bone quality was assessed by TBS. Low vertebral trabecular bone quality was defined as TBS ≤ 1.300. Multivariate logistic regression analyses were used to identify risk factors of low TBS. Results: Prevalence of low TBS in RA women was 52%. RA + low TBS were older (61.9 vs. 55.5, p < 0.001) and had higher prevalence of menopause (90% vs. 75%, p = 0.004), hypertension (50% vs. 34%, p ≤ 0.02), and diabetes mellitus (13% vs. 4%, p = 0.02). There were no associations between GC use, neither doses or cumulative doses, and TBS. Multivariate analyses showed the following: age (OR: 1.05, 95% CI: 1.02–1.08) and the presence of diabetes mellitus (OR: 3.30, 95% CI: 1.03–10.60) were associated with a high risk of low vertebral trabecular bone quality in RA. Conclusions: Half of the RA patients had low trabecular bone quality. Older age and diabetes mellitus are important risk factors for low trabecular bone quality in RA. These findings should give alert to early detection of low TBS, establishing strategies aimed at avoiding the consequences of this complication, including vertebral fractures. Full article
(This article belongs to the Section Immunology)
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21 pages, 2039 KiB  
Article
Comprehensive RNA-Seq Analysis of Human Osteoclast Function in Response to Bothrops moojeni Venom Fractions: Pathways of Bone Resorption and Cytoskeletal Disruption
by Fernanda D’Amélio, Hugo Vigerelli, Rodrigo Pinheiro Araldi, Isabel de Fátima Correia Batista, Daniel Carvalho Pimenta and Irina Kerkis
Toxins 2025, 17(7), 358; https://doi.org/10.3390/toxins17070358 - 19 Jul 2025
Viewed by 400
Abstract
This study investigated the effects of Bothrops moojeni (B. moojeni) venom and its high- (HMM) and low-molecular mass (LMM) fractions on human osteoclast (OC) differentiation and function in vitro, aiming to identify novel therapeutics for bone disorders. Venom preparations were applied [...] Read more.
This study investigated the effects of Bothrops moojeni (B. moojeni) venom and its high- (HMM) and low-molecular mass (LMM) fractions on human osteoclast (OC) differentiation and function in vitro, aiming to identify novel therapeutics for bone disorders. Venom preparations were applied at 5 µg/mL (crude venom and HMM) or 1 µg/mL (LMM) from day 4 of peripheral blood mononuclear cell (PBMC) differentiation through terminal OC formation, enabling evaluation across early differentiation, fusion, and maturation stages. RNA sequencing revealed 7793 genes common to all experimental groups, with unique gene expression signatures of 149 (control), 221 (HMM), 248 (crude venom), and 60 (LMM) genes, reflecting distinct molecular responses. The negative control PBMC group exhibited 1013 unique genes enriched in immune-related pathways, consistent with their undifferentiated state. Crude venom induced the broadest transcriptional modulation, upregulating key fusion (CD47) and resorption (CTSK) genes, and altering markers of OC differentiation. The HMM fraction predominantly influenced inflammatory and osteoclastogenic pathways, notably TNF and NF-κB signaling, while the LMM fraction selectively regulated fusion-related genes (e.g., CD44) and immune pathways, indicating targeted modulation of OC activity. Cytokine profiling showed that crude venom and HMM suppressed osteoclastogenic cytokines such as IL-1β and IL-6, supporting their potential use in inflammatory bone diseases. Pathway enrichment analyses confirmed these differential effects on immune response and bone resorption mechanisms. Together, these results demonstrate that B. moojeni venom and its fractions differentially impact OC biology, with crude venom exerting broad effects and HMM and LMM fractions offering more specific modulation. Future studies will isolate bioactive components and assess therapeutic efficacy in animal models of osteoporosis and rheumatoid arthritis. Full article
(This article belongs to the Special Issue Transcriptomic and Proteomic Study on Animal Venom: Looking Forward)
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15 pages, 740 KiB  
Article
Effects of Janus Kinase Inhibitors on Cardio-Vascular Risk in Rheumatic Diseases: A Prospective Pilot Study
by Diana Popescu, Minerva Codruta Badescu, Elena Rezus, Daniela Maria Tanase, Anca Ouatu, Nicoleta Dima, Oana-Nicoleta Buliga-Finis, Evelina Maria Gosav and Ciprian Rezus
J. Clin. Med. 2025, 14(13), 4676; https://doi.org/10.3390/jcm14134676 - 2 Jul 2025
Viewed by 436
Abstract
Background/Objectives: Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) exhibit increased cardiovascular risk, partly attributed to persistent systemic inflammation. Janus kinase inhibitors (JAKi) effectively reduce inflammation, but their impact on cardiovascular risk remains unclear. This pilot study aimed to evaluate the effect [...] Read more.
Background/Objectives: Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) exhibit increased cardiovascular risk, partly attributed to persistent systemic inflammation. Janus kinase inhibitors (JAKi) effectively reduce inflammation, but their impact on cardiovascular risk remains unclear. This pilot study aimed to evaluate the effect of JAKi therapy on systemic inflammation and lipid markers, correlate traditional cardiovascular risk factors with biological parameters, and quantify subclinical atherosclerosis progression. Methods: We conducted a prospective, single-center study including 48 patients receiving JAKi. Clinical, inflammatory, lipid, and vascular parameters were assessed at baseline (T0) and after 12 months (T1). Primary endpoints included changes in carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and carotid plaque presence. Results: Mean cIMT significantly decreased from 0.29 mm to 0.125 mm (p = 0.019), while ABI improved modestly, but not significantly (0.125 to 0.04, p = 0.103). Carotid plaque prevalence increased slightly from 39.6% to 47.9%, p = 0.159. C-reactive protein (CRP) levels declined significantly, while interleukin (IL)-1β levels increased. Lipoprotein(a) [Lp(a)] levels decreased significantly (mean reduction −7.96 mmol/L, p = 0.001). Multivariate regression identified Lp(a) as an independent predictor of carotid plaque at both T0 (p = 0.011) and T1 (p = 0.005). Baseline ABI was a significant predictor of acute cardiovascular events [hazard ratio (HR): 4.614, 95% CI: 1.034–20.596, p = 0.045]. Conclusions: JAKi therapy significantly reduced systemic inflammation and cIMT in patients with autoimmune rheumatic diseases, suggesting a potential benefit in attenuating early vascular changes. However, residual cardiovascular risk remains in patients with low ABI and elevated Lp(a), warranting close monitoring. Full article
(This article belongs to the Special Issue Cardiovascular Risks in Autoimmune and Inflammatory Diseases)
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10 pages, 1531 KiB  
Case Report
A Rare Case of Cerebral Amyloidoma Mimicking Thalamic Glioma in a Rheumatoid Arthritis Patient
by Elyaa Saleh, Nour Abdelaziz, Malaak Ramahi, Antonia Loukousia, Theodossios Birbilis and Dimitrios Kanakis
Pathophysiology 2025, 32(3), 31; https://doi.org/10.3390/pathophysiology32030031 - 1 Jul 2025
Viewed by 356
Abstract
Amyloidosis, often referred to as “the great imitator”, is a condition characterized by the abnormal deposition of amyloid proteins in various tissues, potentially leading to organ dysfunction. When these deposits localize in the brain, they can disrupt neurological function and present with diverse [...] Read more.
Amyloidosis, often referred to as “the great imitator”, is a condition characterized by the abnormal deposition of amyloid proteins in various tissues, potentially leading to organ dysfunction. When these deposits localize in the brain, they can disrupt neurological function and present with diverse clinical manifestations, making diagnosis particularly challenging. Cerebral amyloidosis is a rare entity that frequently mimics other neurological disorders, often resulting in significant delays in recognition and management. This case highlights the diagnostic challenge posed by cerebral amyloidosis and underscores its unique presentation. We present the case of a 76-year-old male with a history of rheumatoid arthritis (RA) who developed progressive right-sided weakness over several months. Three years prior, he experienced numbness on the right side of his face and upper limb. Initial imaging identified a small lesion in the left thalamic region, which was originally diagnosed as a glioma. However, due to the worsening of his clinical symptoms, further evaluation was warranted. Subsequent imaging revealed lesion growth, prompting a biopsy that ultimately confirmed the diagnosis of intracerebral amyloidoma. This case underscores the necessity of considering amyloidosis in the differential diagnosis of atypical neurological deficits, particularly in patients with systemic inflammatory conditions such as RA. The initial presentation of hemiparesis resembling a stroke, coupled with non-specific imaging findings and a prior misdiagnosis of glioma, highlights the complexity of cerebral amyloidosis. Only through brain biopsy was the definitive diagnosis established, emphasizing the need for improved diagnostic modalities to facilitate early detection. Further subtyping of amyloidosis, however, requires mass spectrometry-based proteomics or immunohistochemistry to accurately identify the specific amyloid protein involved. Clinicians should maintain a high index of suspicion for cerebral amyloidosis in patients with RA who present with progressive neurological deficits and atypical brain lesions. Early recognition and accurate diagnosis are essential to guiding appropriate management and improving patient outcomes. Full article
(This article belongs to the Section Systemic Pathophysiology)
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12 pages, 545 KiB  
Systematic Review
Risk of Osteonecrosis of the Jaw in Patients Treated with Zoledronic or Alendronic Acid: A Systematic Review
by Aine Jakonyte, Egle Gustainyte, Zygimantas Petronis, Aviad Hafizov, Audra Janovskiene and Dainius Razukevicius
Medicina 2025, 61(7), 1159; https://doi.org/10.3390/medicina61071159 - 26 Jun 2025
Viewed by 496
Abstract
Background and Objectives: Bisphosphonates (BP) like zoledronic acid (ZA) and alendronic acid (AA) are used for osteoporosis (OP) or other bone-related conditions as well as to prevent the spread of metastases and in rheumatoid arthritis treatment. However, they have been associated with an [...] Read more.
Background and Objectives: Bisphosphonates (BP) like zoledronic acid (ZA) and alendronic acid (AA) are used for osteoporosis (OP) or other bone-related conditions as well as to prevent the spread of metastases and in rheumatoid arthritis treatment. However, they have been associated with an increased risk of osteonecrosis of the jaw (ONJ). This systematic review aimed to assess the incidence and risk of ONJ in osteoporotic patients treated with ZA or AA and evaluate the impact of treatment duration. Material and Methods: The systematic literature review was conducted following PRISMA guidelines. The keywords “Zoledronic acid,” “Alendronic acid,” “Osteoporosis,” and “Osteonecrosis” were searched in PubMed and ScienceDirect databases. Selection criteria included studies on humans written in English, published from 2014. The systematic review protocol was registered in the PROSPERO register under the following number: CRD42024587046. Results: A total of 7 studies with 98,717 osteoporotic patients met the criteria, showing a higher ONJ incidence with ZA than AA. Six studies linked longer BP use to increased ONJ risk, which quadrupled after 5 years of AA use. A positive correlation was found between BP use (≥3 years) and ONJ in OP patients, primarily affecting females over 60. ONJ appeared after 1 year with AA, increasing over time, while ZA-related ONJ emerged as early as 5 months with a higher overall incidence. Conclusions: ZA poses a higher ONJ risk and incidence and earlier onset than AA, occurring within 5 months versus 1 year for AA. These findings emphasize the need for careful monitoring, especially in long-term BP therapy with additional risk factors. Full article
(This article belongs to the Section Dentistry and Oral Health)
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15 pages, 946 KiB  
Article
Insulin Predicts Methotrexate Response by Affecting the Transcription of Methotrexate Target Genes in the Treatment-Naive Rheumatoid Arthritis
by Victoria M. E. Lundgren, Malin C. Erlandsson, Venkataragavan Chandrasekaran, Sofia Töyrä Silfverswärd, Rille Pullerits and Maria I. Bokarewa
Cells 2025, 14(13), 964; https://doi.org/10.3390/cells14130964 - 24 Jun 2025
Viewed by 474
Abstract
Methotrexate (MTX), the most common first-line treatment in rheumatoid arthritis, is often insufficient, with no model capable of predicting response. The RA classification criteria, including autoantibodies and inflammation, were applied to 257 patients with newly diagnosed inflammatory arthritis in the cohort study, estimating [...] Read more.
Methotrexate (MTX), the most common first-line treatment in rheumatoid arthritis, is often insufficient, with no model capable of predicting response. The RA classification criteria, including autoantibodies and inflammation, were applied to 257 patients with newly diagnosed inflammatory arthritis in the cohort study, estimating MTX response. A total of 172 patients received MTX as the first anti-rheumatic drug and response was recorded at 1 year follow-up. A multivariable logistic regression used variables distinct between MTX-responders and non-responders to build the predictive model of response. Overall, 53.5% of MTX treated patients responded. Non-responders were frequently autoantibody positive, and responders were older, had lower RA classification scores, frequent corticosteroid use, and high insulin levels at baseline. Inflammation parameters were comparable between the groups. In the multiple regression analysis, the RA classification score and age at the first visit were strong predictors of MTX response (AUC 0.697, p < 0.0001). Including blood levels of insulin and IFNg improved AUC to 0.782 (p < 0.0001), offering early discrimination between responders and non-responders with high accuracy. Cellular experiments showed that insulin could be used to estimate MTX response by demonstrating that insulin changed the transcription of MTX target genes in the folate metabolism after exposing CD4+ cells ex vivo, which could facilitate MTX response in immune cells. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Targets of Autoimmune Diseases)
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23 pages, 986 KiB  
Review
COVID-19 and a Tale of Three Drugs: To Repurpose, or Not to Repurpose–That Was the Question
by Chris R. Triggle and Ross MacDonald
Viruses 2025, 17(7), 881; https://doi.org/10.3390/v17070881 - 23 Jun 2025
Viewed by 946
Abstract
On 11 March 2020, the World Health Organisation (WHO) declared a global pandemic caused by the SARS-CoV-2 coronavirus that earlier in February 2020 the WHO had named COVID-19 (coronavirus disease 2019). There were neither drugs nor vaccines that were known to be effective [...] Read more.
On 11 March 2020, the World Health Organisation (WHO) declared a global pandemic caused by the SARS-CoV-2 coronavirus that earlier in February 2020 the WHO had named COVID-19 (coronavirus disease 2019). There were neither drugs nor vaccines that were known to be effective against the virus, stimulating an urgent worldwide search for treatments. An evaluation of existing drugs by ‘repurposing’ was initiated followed by a transition to de novo drug discovery. Repurposing of an already approved drug may accelerate the introduction of that drug into clinical use by circumventing early, including preclinical studies otherwise essential for a de novo drug and reducing development costs. Early in the pandemic three drugs were identified as repurposing candidates for the treatment of COVID-19: (i) hydroxychloroquine, an anti-malarial also used to treat rheumatoid arthritis and lupus; (ii) ivermectin, an antiparasitic approved for both human and veterinary use; (iii) remdesivir, an anti-viral originally developed to treat hepatitis C. The scientific evidence, both for and against the efficacy of these three drugs as treatments for COVID-19, vied with public demand and politicization as unqualified opinions clashed with evidence-based medicine. To quote Hippocrates, “There are in fact two things, science and opinion; the former begets knowledge, the latter ignorance”. Full article
(This article belongs to the Section Coronaviruses)
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19 pages, 1442 KiB  
Review
The Key Role of Porphyromonas gingivalis in the Pathogenesis of Periodontitis Linked with Systemic Diseases
by Bianca Maria Messina, Cristina Grippaudo, Alessandro Polizzi, Andrea Blasi and Gaetano Isola
Appl. Sci. 2025, 15(12), 6847; https://doi.org/10.3390/app15126847 - 18 Jun 2025
Cited by 1 | Viewed by 837
Abstract
New technologies and tools are emerging in periodontology and oral health. Periodontitis is a chronic inflammatory condition that destroys the supporting tissues of the teeth and ultimately leads to tooth loss. As one of the most prevalent oral conditions, periodontitis endangers the oral [...] Read more.
New technologies and tools are emerging in periodontology and oral health. Periodontitis is a chronic inflammatory condition that destroys the supporting tissues of the teeth and ultimately leads to tooth loss. As one of the most prevalent oral conditions, periodontitis endangers the oral health of 70% of people worldwide, and has been increasingly linked to various systemic diseases. In this regard, Porphyromonas gingivalis (P. gingivalis) is a key pathogen in the oral microbiome and a Gram-negative oral anaerobic bacterium that plays a key role in the pathogenesis of periodontitis. Porphyromonas gingivalis can express various virulence factors to evade innate and adaptive immunities, which causes P. gingivalis to survive and propagate in the host, destroy periodontal tissues, and contribute to systemic diseases. This narrative review aims to summarize the current knowledge on the impact of P. gingivalis in oral microbiome formation and its mechanistic links to systemic diseases such as cardiovascular disease, diabetes mellitus, rheumatoid arthritis, and Alzheimer’s disease. This review will explore the pathogenic mechanisms employed by P. gingivalis, including immune evasion, dissemination, and molecular mimicry, and evaluate the clinical and epidemiological evidence linking periodontitis with systemic health outcomes. By consolidating these insights, this review seeks to highlight the importance of periodontal health in preventing systemic diseases and propose potential therapeutic interventions targeting P. gingivalis. These findings highlight that early diagnosis and effective treatment of periodontitis, particularly targeting P. gingivalis, are essential not only to preserving oral health but also to reducing the risk and progression of systemic diseases. Full article
(This article belongs to the Section Applied Biosciences and Bioengineering)
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12 pages, 779 KiB  
Article
The Association Between Serum Isthmin-1 and Disease Activity, Inflammation, and Autoantibody Status in Rheumatoid Arthritis
by Burak Oz, Ibrahım Gunduz, Gulsah Yamancan, Yusuf Dogan, Ramazan Fazıl Akkoc, Nevzat Gozel, Mustafa Gur, Ahmet Karatas and Suleyman Serdar Koca
Diagnostics 2025, 15(11), 1316; https://doi.org/10.3390/diagnostics15111316 - 23 May 2025
Viewed by 487
Abstract
Background/Objectives: Isthmin-1 (ISM1) is a secreted protein involved in immune regulation, inflammation, and angiogenesis. Although ISM1 has been implicated in chronic inflammatory conditions, its clinical relevance in rheumatoid arthritis (RA) remains unknown. This study aimed to evaluate serum ISM1 levels in RA [...] Read more.
Background/Objectives: Isthmin-1 (ISM1) is a secreted protein involved in immune regulation, inflammation, and angiogenesis. Although ISM1 has been implicated in chronic inflammatory conditions, its clinical relevance in rheumatoid arthritis (RA) remains unknown. This study aimed to evaluate serum ISM1 levels in RA patients and assess their associations with disease activity, autoantibody status, and inflammatory markers. Methods: This cross-sectional study included 90 RA patients fulfilling the 2010 ACR/EULAR criteria and 30 age- and sex-matched healthy controls. Serum ISM1 concentrations were measured using ELISA. Disease activity was assessed using DAS28-CRP and DAS28-ESR. Statistical analyses included group comparisons, correlation testing, multivariate linear regression, and ROC curve analysis to evaluate the predictive performance of ISM1 for remission or low disease activity. Results: Serum ISM1 levels were significantly lower in RA patients than in controls (454 ± 378 vs. 972 ± 809 ng/L, p < 0.001). ISM1 concentrations were inversely correlated with CRP, ESR, and both DAS28 indices. Multivariate regression confirmed independent associations between lower ISM1 concentrations and higher disease activity. ISM1 levels were significantly reduced in RF- and anti-CCP-positive patients, as well as in treatment-naïve early RA. ROC analysis identified a cut-off value of 673.73 ng/L for predicting remission or low disease activity, with an AUC of 0.713 (95% CI: 0.596–0.820), 100% specificity, and 38.9% sensitivity. Conclusions: This study is the first to demonstrate that serum ISM1 is independently associated with disease activity and autoantibody positivity in RA. High ISM1 levels may serve as a specific indicator of clinical remission or low disease activity, supporting its potential as a non-invasive biomarker for disease monitoring. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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17 pages, 1186 KiB  
Article
Ultrasound Predictors for Persistence or a Change in the Diagnosis of Rheumatoid Arthritis After 5 Years—A Prospective Cohort Study of Patients with Early Rheumatoid Arthritis
by Tanya Sapundzhieva, Lyubomir Sapundzhiev, Martin Mitev, Rositsa Karalilova and Anastas Batalov
Biomedicines 2025, 13(5), 1226; https://doi.org/10.3390/biomedicines13051226 - 19 May 2025
Viewed by 866
Abstract
Aim: To identify ultrasound (US) predictors of persistence or change in the diagnosis of rheumatoid arthritis (RA) after five years in a cohort of patients with early RA. Patients and Methods: One hundred and twenty patients with early arthritis who met the 2010 [...] Read more.
Aim: To identify ultrasound (US) predictors of persistence or change in the diagnosis of rheumatoid arthritis (RA) after five years in a cohort of patients with early RA. Patients and Methods: One hundred and twenty patients with early arthritis who met the 2010 ACR/EULAR classification criteria for RA were followed for a period of five years. The US assessment at baseline included a bilateral evaluation of the wrists, second to fifth metacarpophalangeal (MCP) joints, second to fifth proximal interphalangeal (PIP) joints, the IV and VI extensor compartments of the wrists, and the flexor tendons of the second to fifth fingers. This evaluation was conducted using both grayscale ultrasound (GSUS) and power Doppler ultrasound (PDUS). The following scores were recorded for each patient: synovitis score, mini-enthesitis score (including paratenonitis of the finger extensor tendon at the MCP joint, central slip enthesitis at the PIP joint, pseudotenosynovitis, and the A1 pulley of the second finger), finger flexor tenosynovitis score, and tenosynovitis score for the IV and VI wrist extensor compartments. The receiver operating characteristic (ROC) curve was utilized to identify the ultrasound predictors for either maintaining or revising an initial diagnosis of RA. Results: At month 6, 82 (68%) patients were classified as having RA according to 1987 ACR RA criteria, 23 (19.2%) were diagnosed with psoriatic arthritis (PsA), 10 (8.3%) with systemic connective tissue disease (SCTD)–8 (6.7%) patients with Sjogren Syndrome and 2 (1.7%) patients with systemic lupus erythematosus (SLE)–and 5 (4.2%) patients with calcium pyrophosphate deposition disease (CPPD). The most significant predictor of RA in the fifth year was the VI extensor compartment tenosynovitis score, with an AUC of 0.915 and a criterion value > 0, associated with a sensitivity of 82.93% and a specificity of 100% (p < 0.001). The PDUS synovitis score demonstrated the second-best prognostic ability with an AUC of 0.823, a criterion value > 2, a sensitivity of 82.93%, and a specificity of 73.68% (p < 0.001). The mini-enthesitis score showed the best prognostic ability of a PsA diagnosis with an AUC of 0.998, a criterion value > 1, a sensitivity of 95.65%, and a specificity of 100% (p < 0.001). The paratenonitis score, pseudotenosynovitis score, and thickened A1 pulley were also predictive of PsA diagnosis with AUCs of 0.977, 0.955, and 0.919, respectively (p < 0.001 for all). Conclusions: Nearly one-third of the patients who were initially classified as having RA had their diagnosis revised at the end of the fifth year. Ultrasound of joints, tendons, and mini-entheses at baseline may serve as potential imaging predictive biomarkers for persistence or change in diagnosis after 5 years. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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13 pages, 3751 KiB  
Article
Additive Value of Rheumatoid Factor Isotypes in Sjögren’s Syndrome Patients with Joint Complaints of Different Etiologies—Can Rheumatoid Factor IgA Serve as an Early, Poor Prognostic Biomarker Candidate?
by Zsófia Aradi, Bernadett Bói, Gábor Nagy, Péter Antal-Szalmás, Kincső Mezei, Ildikó Fanny Horváth and Antónia Szántó
Int. J. Mol. Sci. 2025, 26(10), 4797; https://doi.org/10.3390/ijms26104797 - 16 May 2025
Viewed by 479
Abstract
The aim of the paper was to characterize rheumatoid factor IgA, IgG, and IgM isotypes in patients with Sjögren’s syndrome (SS) subsets, based on the absence or presence of joint complaints of different etiologies. In total, 164 SS patients were grouped based on [...] Read more.
The aim of the paper was to characterize rheumatoid factor IgA, IgG, and IgM isotypes in patients with Sjögren’s syndrome (SS) subsets, based on the absence or presence of joint complaints of different etiologies. In total, 164 SS patients were grouped based on whether they had polyarthritis as an extraglandular manifestation (n = 73, SS+pa), rheumatoid arthritis as an associated autoimmune disorder (n = 46, SS+RA), or Sjögren’s syndrome without inflammatory joint pain (n = 45, SS). The highest IgA rheumatoid factor isotype levels were detected in SS patients, whereas the lowest levels were found in the SS+RA group, without a significant difference. Neither IgG nor IgM RF differed significantly between the patient subclasses. In addition to other disease-specific markers, seropositive patients who were seropositive for any RF isotype were significantly more frequently anti-Ro/SS-A and anti-La/SS-B positive and had higher ESSDAI levels. In SS and SS+pa patients, a strong negative correlation was observed between IgA RF and age, whereas a strong positive correlation was found between IgA RF and ESSDAI, RF, IgA, IgG, anti-Ro/SS-A, and anti-La/SS-B levels. High total IgG levels together with high IgA RF levels occurred most frequently in SS patients (p = 0.05), whereas the combination of normal IgG and high IgM RF was significantly more frequent in the SS+RA group. The co-occurrence of high total IgG and normal IgM RF did not differ significantly between the patient subsets; however, this was the combination with the highest sensitivity (94.5%) for SS+pa patients. Based on our findings, rheumatoid factor isotypes have an additive value in the differentiation of non-erosive polyarthritis and erosive rheumatoid arthritis during the disease course of patients with Sjögren’s syndrome. All rheumatoid factor isotypes predict a more severe disease course, but IgA RF may serve as a candidate for being an early, poor prognostic factor for SS patients. Full article
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20 pages, 2067 KiB  
Article
Explainable Boosting Machines Identify Key Metabolomic Biomarkers in Rheumatoid Arthritis
by Fatma Hilal Yagin, Cemil Colak, Abdulmohsen Algarni, Ali Algarni, Fahaid Al-Hashem and Luca Paolo Ardigò
Medicina 2025, 61(5), 833; https://doi.org/10.3390/medicina61050833 - 30 Apr 2025
Viewed by 986
Abstract
Background and Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by joint inflammation and pain. Metabolomics approaches, which are high-throughput profiling of small molecule metabolites in plasma or serum in RA patients, have so far provided biomarker discovery in the [...] Read more.
Background and Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by joint inflammation and pain. Metabolomics approaches, which are high-throughput profiling of small molecule metabolites in plasma or serum in RA patients, have so far provided biomarker discovery in the literature for clinical subgroups, risk factors, and predictors of treatment response using classical statistical approaches or machine learning models. Despite these recent developments, an explainable artificial intelligence (XAI)-based methodology has not been used to identify RA metabolomic biomarkers and distinguish patients with RA. This study constructed a XAI-based EBM model using global plasma metabolomics profiling to identify metabolites predictive of RA patients and to develop a classification model that can distinguish RA patients from healthy controls. Materials and Methods: Global plasma metabolomics data were analysed from RA patients (49 samples) and healthy individuals (10 samples). SMOTE technique was used for class imbalance in data preprocessing. EBM, LightGBM, and AdaBoost algorithms were applied to generate a discriminatory model between RA and controls. Comprehensive performance metrics were calculated, and the interpretability of the optimal model was assessed using global and local feature descriptions. Results: A total of 59 samples were analysed, 49 from RA patients, and 10 from healthy subjects. The EBM generated better results than LightGBM and AdaBoost by attaining an AUC of 0.901 (95% CI: 0.847–0.955) with 87.8% sensitivity which helps prevent false negative early RA diagnosis. The primary biomarkers EBM-based XAI identified were N-acetyleucine, pyruvic acid, and glycerol-3-phosphate. EBM global explanation analysis indicated that elevated pyruvic acid levels were significantly correlated with RA, whereas N-acetyleucine exhibited a nonlinear relationship, implying possible protective effects at specific concentrations. Conclusions: This study underscores the promise of XAI and evidence-based medicine methodology in developing biomarkers for RA through metabolomics. The discovered metabolites offer significant insights into RA pathophysiology and may function as diagnostic biomarkers or therapeutic targets. Incorporating EBM methodologies integrated with XAI improves model transparency and increases the therapeutic applicability of predictive models for RA diagnosis/management. Furthermore, the transparent structure of the EBM model empowers clinicians to understand and verify the reasoning behind each prediction, thereby fostering trust in AI-assisted decision-making and facilitating the integration of metabolomic insights into routine clinical practice. Full article
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11 pages, 491 KiB  
Article
Impact of Foot Surgery and Pharmacological Treatments on Functionality and Pain in Rheumatoid Arthritis: A Five-Year Longitudinal Study
by Amparo Campos-Cano, Alejandro Castillo-Dominguez, Ana-Belen Ortega-Avila, Laura Ramos-Petersen, Gabriel Gijon-Nogueron, Maria-Jose Perez-Galan and Andres Reinoso-Cobo
Healthcare 2025, 13(9), 1004; https://doi.org/10.3390/healthcare13091004 - 27 Apr 2025
Viewed by 501
Abstract
Background: Rheumatoid arthritis (RA) frequently leads to foot deformities, significantly impacting pain, mobility, and quality of life. Surgical and pharmacological treatments are prescribed to manage symptoms, but their long-term effects on foot function remain unclear. This study evaluates the impact of different treatment [...] Read more.
Background: Rheumatoid arthritis (RA) frequently leads to foot deformities, significantly impacting pain, mobility, and quality of life. Surgical and pharmacological treatments are prescribed to manage symptoms, but their long-term effects on foot function remain unclear. This study evaluates the impact of different treatment approaches, including surgery, methotrexate (MTX), and biological therapy (Bio), on foot functionality and pain progression over five years. Methods: A longitudinal cohort study was conducted with 103 RA patients classified into five groups: surgery, MTX < 10 years, MTX ≥ 10 years, Bio < 10 years, and Bio ≥ 10 years. Data from 2018 and 2023 were compared using the Visual Analog Scale (VAS), the Manchester Foot Pain and Disability Index (MFPDI), and the Foot Function Index (FFI). Statistical analyses included ANOVA, Kruskal–Wallis, and ROC curve analysis to assess differences between groups and identify key progression factors. Results: Patients with ≥10 years of disease duration and non-biological treatment (MTX ≥ 10 years) experienced the most severe deterioration in foot function, with a mean FFI increase of +11.89 points (p < 0.01). In contrast, MTX < 10 years was the only group to show an improvement in foot function (FFI: −5.29, p = 0.02). The surgery group exhibited moderate but highly variable functional changes, while patients on biological therapy showed less progression in pain and disability compared to their non-biologic counterparts. Hallux abductus valgus severity increased across all groups. Conclusions: Patients with long-standing RA on non-biologic therapy exhibited the greatest decline in foot function, whereas early treatment with MTX (<10 years of disease duration) appeared to slow deterioration. Surgery did not consistently provide functional benefits, and biologics helped mitigate progression, though outcomes varied. These findings underscore the importance of early intervention and personalized treatment strategies for foot preservation in RA. Full article
(This article belongs to the Special Issue Innovative Strategies in Rheumatology Care)
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28 pages, 1171 KiB  
Review
From Joints to the Heart: An Integrated Perspective on Systemic Inflammation
by Diana Elena Cosău, Irina Iuliana Costache Enache, Alexandru Dan Costache, Ionuț Tudorancea, Codrina Ancuța, Dragomir Nicolae Șerban, Codruța Minerva Bădescu, Cătălin Loghin and Ionela Lăcrămioara Șerban
Life 2025, 15(4), 629; https://doi.org/10.3390/life15040629 - 9 Apr 2025
Viewed by 779
Abstract
Background: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease which predominantly affects joints, but it can also lead to significant extra-articular complications, particularly cardiovascular disease (CVD). Chronic systemic inflammation promotes endothelial dysfunction and accelerates atherosclerosis, increasing cardiovascular risk. Methods: Current data were analyzed [...] Read more.
Background: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease which predominantly affects joints, but it can also lead to significant extra-articular complications, particularly cardiovascular disease (CVD). Chronic systemic inflammation promotes endothelial dysfunction and accelerates atherosclerosis, increasing cardiovascular risk. Methods: Current data were analyzed to explore the mechanisms between RA and CVD, focusing on systemic inflammation, pro-inflammatory cytokine patways (IL-1, IL-6, TNF, and JAK-STAT), and their interactions with traditional cardiovascular risk factors. Recent studies and clinical guidelines were reviewed to highlight gaps and advances in risk assessment and management. Results: Persistent disease activity and the presence of autoantibodies significantly increase cardiovascular risk in RA contributing to atherosclerosis and major cardiovascular events. Data also suggest that anti-inflammatory treatments, including methotrexate and biologic agents, may lower this risk. Conclusion: This review highlights the pathophysiological mechanisms between RA and CVD, and the need for early diagnosis and active monitoring to identify and assess cardiovascular risk. A multidisciplinary approach, involving rheumatologists and cardiologists is essential for optimizing cardiovascular risk management and improving patient outcomes. Optimization of cardiovascular risk management strategies in patients with RA should be an essential component of current medical practice, with the main goal of reducing morbidity and mortality from cardiovascular complications. Full article
(This article belongs to the Special Issue Interdisciplinarity in Cardiovascular Pathology)
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