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Search Results (243)

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Keywords = Ankylosing spondylitis

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11 pages, 1093 KiB  
Article
Diagnostic Accuracy of Shear Wave Elastography Versus Ultrasound in Plantar Fasciitis Among Patients with and Without Ankylosing Spondylitis
by Mahyar Daskareh, Mahsa Mehdipour Dalivand, Saeid Esmaeilian, Aseme Pourrajabi, Seyed Ali Moshtaghioon, Elham Rahmanipour, Ahmadreza Jamshidi, Majid Alikhani and Mohammad Ghorbani
Diagnostics 2025, 15(15), 1967; https://doi.org/10.3390/diagnostics15151967 - 5 Aug 2025
Abstract
Background: Plantar fasciitis (PF) is a common enthesopathy in patients with ankylosing spondylitis (AS). Shear wave elastography (SWE) and the Belgrade ultrasound enthesitis score (BUSES) may detect PF, but their comparative diagnostic performance is unclear. Objective: To compare SWE with the BUSES for [...] Read more.
Background: Plantar fasciitis (PF) is a common enthesopathy in patients with ankylosing spondylitis (AS). Shear wave elastography (SWE) and the Belgrade ultrasound enthesitis score (BUSES) may detect PF, but their comparative diagnostic performance is unclear. Objective: To compare SWE with the BUSES for identifying PF in individuals with and without AS. Methods: In this cross-sectional study, 96 participants were stratified into AS and non-AS populations, each further divided based on the presence or absence of clinical PF. Demographic data, the American Orthopedic Foot and Ankle Society Score (AOFAS), and the BASDAI score were recorded. All subjects underwent grayscale ultrasonography, the BUSES scoring, and SWE assessment of the plantar fascia. Logistic regression models were constructed for each population, controlling for age, body mass index (BMI), and fascia–skin distance. ROC curve analyses were performed to evaluate diagnostic accuracy. Results: In both AS and non-AS groups, SWE and the BUSES were significant predictors of PF (p < 0.05). SWE demonstrated slightly higher diagnostic accuracy, with area under the curve (AUC) values of 0.845 (AS) and 0.837 (non-AS), compared to the BUSES with AUCs of 0.785 and 0.831, respectively. SWE also showed stronger adjusted odds ratios in regression models. The interobserver agreement was good to excellent for both modalities. Conclusions: Both SWE and the BUSES are effective for PF detection, with SWE offering marginally superior diagnostic performance, particularly in AS patients. SWE may enhance the early identification of biomechanical changes in the plantar fascia. Full article
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56 pages, 1035 KiB  
Review
Trace Elements—Role in Joint Function and Impact on Joint Diseases
by Łukasz Bryliński, Katarzyna Brylińska, Filip Woliński, Jolanta Sado, Miłosz Smyk, Olga Komar, Robert Karpiński, Marcin Prządka and Jacek Baj
Int. J. Mol. Sci. 2025, 26(15), 7493; https://doi.org/10.3390/ijms26157493 - 2 Aug 2025
Viewed by 423
Abstract
Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a [...] Read more.
Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a serious social problem. Risk factors for the development of these diseases include overweight and obesity, gender, and intestinal microbiome disorders. Another factor that is considered to influence joint diseases is trace elements. Under normal conditions, elements such as iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), nickel (Ni) selenium (Se), boron (B), and silicon (Si) are part of enzymes involved in reactions that determine the proper functioning of cells, regulate redox metabolism, and determine the maturation of cells that build joint components. However, when the normal concentration of the above-mentioned elements is disturbed and toxic elements are present, dangerous joint diseases can develop. In this article, we focus on the role of trace elements in joint function. We describe the molecular mechanisms that explain their interaction with chondrocytes, osteocytes, osteoblasts, osteoclasts, and synoviocytes, as well as their proliferation, apoptosis, and extracellular matrix synthesis. We also focus on the role of these trace elements in the pathogenesis of joint diseases: rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE). We describe the roles of increased or decreased concentrations of individual elements in the pathogenesis and development of joint diseases and their impact on inflammation and disease progression, referring to molecular mechanisms. We also discuss their potential application in the treatment of joint diseases. Full article
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16 pages, 430 KiB  
Article
Evaluating Secukinumab as Treatment for Axial Spondyloarthritis and Psoriatic Arthritis in Patients with Comorbidities: Multicenter Real-Life Experience
by Tuğba Ocak, Burcu Yağız, Belkıs Nihan Coşkun, Gamze Akkuzu, Ayşe Nur Bayındır Akbaş, Özlem Kudaş, Elif İnanç, Özge Yoğurtçu, Fatma Başıbüyük, Sezgin Zontul, Fatih Albayrak, Zeynel Abidin Akar, Saliha Sunkak, Selime Ermurat, Dilek Tezcan, Adem Küçük, Servet Yolbaş, İsmail Sarı, Murat Yiğit, Servet Akar, Bünyamin Kısacık, Cemal Bes, Ediz Dalkılıç and Yavuz Pehlivanadd Show full author list remove Hide full author list
J. Clin. Med. 2025, 14(15), 5181; https://doi.org/10.3390/jcm14155181 - 22 Jul 2025
Viewed by 362
Abstract
Background: Secukinumab is a fully human monoclonal antibody that targets interleukin (IL)-17A and is used to treat axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Treating axSpA and PsA can be challenging in patients with comorbidities. In this multicenter retrospective study, we aimed [...] Read more.
Background: Secukinumab is a fully human monoclonal antibody that targets interleukin (IL)-17A and is used to treat axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Treating axSpA and PsA can be challenging in patients with comorbidities. In this multicenter retrospective study, we aimed to evaluate the efficacy and safety of secukinumab treatment in patients with axSpA and PsA who had a history of tuberculosis, multiple sclerosis (MS), or congestive heart failure (CHF). Methods: The study included 44 patients with a diagnosis of axSpA and PsA and a history of tuberculosis, MS, or CHF who received secukinumab treatment at 13 centers in our country. Erythrocyte sedimentation rate, C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index, Ankylosing Spondylitis Disease Activity Score CRP, visual analog scale, and Disease Activity Score-28 CRP markers at months 0, 3, and 12 of secukinumab treatment were analyzed. Alongside this, tuberculosis, MS, and CHF were evaluated at follow-up using clinical assessments and imaging methods such as chest radiographs, brain magnetic resonance, and echocardiography. Results: A statistically significant improvement in inflammatory markers and disease activity scores was observed in patients treated with secukinumab. There was no reactivation in patients with a history of tuberculosis. In most MS patients, the disease was stable, while clinical and radiological improvement was observed in one patient. No worsening of CHF stage was observed in patients with a history of CHF. Conclusions: With regular clinical monitoring, secukinumab may be an effective and safe treatment option for axSpA and PsA patients with a history of tuberculosis, MS, or CHF. Full article
(This article belongs to the Section Dermatology)
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19 pages, 6158 KiB  
Article
Causal Inference and Shared Molecular Pathways in Crohn’s Disease, Celiac Disease, and Ankylosing Spondylitis: Integrative Mendelian Randomization and Transcriptomic Analysis
by Ya Li, Shihao Xu, Mingzhu Zhang, Xin Yang and Zhengqiang Wei
Int. J. Mol. Sci. 2025, 26(13), 6451; https://doi.org/10.3390/ijms26136451 - 4 Jul 2025
Viewed by 466
Abstract
This study explored the causal and molecular overlap among Crohn’s disease (CD), celiac disease (CeD), and ankylosing spondylitis (AS). Bidirectional Mendelian randomization revealed significant causal associations between each disease pair. Transcriptomic analyses identified three consistently upregulated hub genes—P2RY8, ITGAL, and GPR65—across all conditions, [...] Read more.
This study explored the causal and molecular overlap among Crohn’s disease (CD), celiac disease (CeD), and ankylosing spondylitis (AS). Bidirectional Mendelian randomization revealed significant causal associations between each disease pair. Transcriptomic analyses identified three consistently upregulated hub genes—P2RY8, ITGAL, and GPR65—across all conditions, which were validated in independent datasets and inflammatory cell models. Functional enrichment suggested these genes are involved in immune signaling and mucosal inflammation. Regulatory network and molecular docking analyses further highlighted Trichostatin A as a potential therapeutic agent. These findings reveal shared genetic and immune-related mechanisms, offering novel targets for cross-disease treatment strategies. Full article
(This article belongs to the Section Molecular Biology)
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11 pages, 362 KiB  
Article
Predictors for Improvement of Global Functioning in Patients with Axial Spondyloarthritis
by Kwi Young Kang, Brittany L. Adler and Tae Hwan Chung
J. Clin. Med. 2025, 14(13), 4474; https://doi.org/10.3390/jcm14134474 - 24 Jun 2025
Viewed by 334
Abstract
Objectives: We aimed to investigate the factors associated with changes in the global functioning of patients with axial spondyloarthritis (axSpA) and to identify predictors of improvement. Methods: One-hundred-and-eighty-five patients enrolled in the Incheon Saint Mary’s axSpA prospective observational cohort were evaluated. [...] Read more.
Objectives: We aimed to investigate the factors associated with changes in the global functioning of patients with axial spondyloarthritis (axSpA) and to identify predictors of improvement. Methods: One-hundred-and-eighty-five patients enrolled in the Incheon Saint Mary’s axSpA prospective observational cohort were evaluated. Global functioning was assessed at baseline and at 1-year follow-up using the ASAS health index (HI). Improvement was defined as a reduction in the ASAS HI of ≥3. Physical function was assessed using the Bath Ankylosing Spondylitis Functional Index (BASFI). Disease activity measures included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), and C-reactive protein (CRP) levels. Predictors of improved global functioning were identified by logistic regression analysis. Results: Nineteen patients (10%) showed improved global functioning at 1-year follow-up versus baseline. Univariate linear regression analysis identified body mass index at baseline, the use of TNF inhibitors, a change in the BASFI and BASDAI, and changes in CRP levels as being associated with changes in the ASAS HI. Multivariate analysis revealed that changes in the BASFI and BASDAI were associated independently with a change in the ASAS HI. Univariate logistic regression analysis revealed that a decrease in the BASFI, BASDAI, ASDAS, and CRP levels predicted improved global functioning. Multivariate analysis identified a decrease in the BASFI and BASDAI as a significant predictor of improved global functioning (odds ratio (95% CI) = 1.465 (1.006–2.135) and 1.414 (1.044–1.914), respectively). Conclusions: Changes in physical function and disease activity were associated independently with changes in global functioning assessed by the ASAS HI in axSpA. A decrease in the BASFI and BASDAI was a significant predictor of improvement in the ASAS HI. Full article
(This article belongs to the Section Immunology)
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14 pages, 790 KiB  
Article
Role of High Serum Tenascin C Levels as Potential Biomarker of Persistent Inflammation in Patients with Ankylosing Spondylitis Despite Treatment with cs-DMARDS or Anti-TNF Agents
by Alejandro Martelli-Garcia, Yussef Esparza-Guerrero, Heriberto Jacobo-Cuevas, Ana Miriam Saldaña-Cruz, Norma Guadalupe Gonzalez-Montoya, Cesar Arturo Nava-Valdivia, Eli Efrain Gomez-Ramirez, Maria Luisa Vazquez-Villegas, Juan Manuel Ponce-Guarneros, Melissa Ramirez-Villafaña, Norma Alejandra Rodriguez-Jimenez, Alberto Daniel Rocha-Muñoz, Ernesto German Cardona-Muñoz, Jaime Morales-Romero, Laura Gonzalez-Lopez and Jorge Ivan Gamez-Nava
Diagnostics 2025, 15(12), 1457; https://doi.org/10.3390/diagnostics15121457 - 7 Jun 2025
Viewed by 666
Abstract
Background/Objectives: Ankylosing spondylitis (AS) is a severe chronic inflammatory rheumatic disease involving the spine, sacroiliacs, and peripheral joints. A lack of therapeutic response leads to severe sequelae. Currently, new markers are being tested to identify patients with poor outcomes. Tenascin C (TNC) is [...] Read more.
Background/Objectives: Ankylosing spondylitis (AS) is a severe chronic inflammatory rheumatic disease involving the spine, sacroiliacs, and peripheral joints. A lack of therapeutic response leads to severe sequelae. Currently, new markers are being tested to identify patients with poor outcomes. Tenascin C (TNC) is involved in triggering some relevant mechanisms of inflammation. Today, it remains unclear whether TNC levels might be useful as a biomarker of persistent activity. The aim of this study was to evaluate in AS whether serum levels of tenascin C are associated with persistent disease activity despite treatment. Methods: We included AS patients who had been treated with conventional synthetic disease-modifying antirheumatic drugs (cs-DMARDS) or anti-TNF agents for at least three months in a cross-sectional study. Response was assessed with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); scores ≥ 4 indicate persistent disease activity, while scores < 4 indicate inactive disease. Serum TNC levels, C-reactive protein (CRP) levels, and Erythrocyte Sedimentation Rate (ESR) were determined through the ELISA technique, nephelometry, and the Westergren method, respectively. Results: We evaluated 58 patients with AS (62.1% men); of them, 33 (56.9%) had persistent active disease (BASDAI ≥ 4) despite treatment and 25 (43.1%) had inactive disease (BASDAI < 4). The median TNC level was 18.6 ng/mL. BASDAI correlated with TNC levels (rho: 0.528, p < 0.001), CRP (0.352, p = 0.007), and ESR (0.342, p = 0.009). Patients with persistently active AS had higher serum TNC levels than those with inactive AS (35.2 vs. 6 ng/mL, p < 0.001). No differences in TNC level were found in patients treated with cs-DMARDS vs. anti-TNF agents. The ROC curve for serum tenascin C in active AS patients had an area under the curve = 0.78 (CI 95%: 0.65–0.91) with optimal serum tenascin C cutoff (>13.85 ng/mL). Sensitivity for detecting active AS was higher with TNC compared to ESR and CRP. Conclusions: We suggest that an elevated TNC level may be a useful biomarker of persistent disease activity despite treatment in AS; further studies should investigate the role of TNC levels in predicting the progression of the disease. Full article
(This article belongs to the Special Issue Recent Advances in Clinical Biochemical Testing)
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13 pages, 631 KiB  
Article
How Do Fear-Avoidance and Catastrophizing Pain Beliefs Affect Functional Status and Disease Activity in Axial Spondyloarthritis?
by Carlos Fernández-Morales, María de los Ángeles Cardero-Durán, Manuel Albornoz-Cabello and Luis Espejo-Antúnez
Medicina 2025, 61(6), 1039; https://doi.org/10.3390/medicina61061039 - 5 Jun 2025
Viewed by 563
Abstract
Background and Objectives: The objective of our study was to describe the biopsychosocial profile of individuals diagnosed with axial spondyloarthritis (AxSpA) and to analyze how their clinical characteristics interact with disease activity. Materials and Methods: An observational study was conducted, involving [...] Read more.
Background and Objectives: The objective of our study was to describe the biopsychosocial profile of individuals diagnosed with axial spondyloarthritis (AxSpA) and to analyze how their clinical characteristics interact with disease activity. Materials and Methods: An observational study was conducted, involving 28 participants diagnosed with AxSpA. We evaluated clinical outcomes (perceived pain, range of motion [RoM], pressure pain threshold [PPT], and proprioceptive acuity), psychosocial outcomes (the Pain Catastrophizing Scale [PCS], Tampa Scale of Kinesiophobia [TSK-11], and the Fear-Avoidance Beliefs Questionnaire [FABQ]), and AxSpA-specific indices (the Bath Ankylosing Spondylitis Metrology Index [BASMI], Bath Ankylosing Spondylitis Functional Index [BASFI], and Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Data were analyzed using Spearman’s correlation coefficients and simple and multiple linear regression models. Results: Cervical and lumbar RoM values were reduced compared to established normative values for the general population. Significant associations were found between perceived pain, pain catastrophizing, and FABQ scores with both BASDAI and BASFI (p < 0.05). The interaction between perceived pain and pain catastrophizing (p < 0.001) accounted for 45.7% of the variance in BASDAI, while the interaction between perceived pain and FABQ (p < 0.001) explained 52.1% of the variance in BASDAI. Conclusions: The biopsychosocial profile of patients with AxSpA is characterized by moderate-intensity perceived pain and reduced cervical and lumbar mobility. The observed associations between BASDAI, pain catastrophizing, and fear-avoidance beliefs underscore the influence of psychosocial factors on disease progression. Full article
(This article belongs to the Section Psychiatry)
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33 pages, 1280 KiB  
Systematic Review
The Genetic Background of Ankylosing Spondylitis Reveals a Distinct Overlap with Autoimmune Diseases: A Systematic Review
by Theodora Zormpa, Trias Thireou, Apostolos Beloukas, Dimitrios Chaniotis, Rebecca Golfinopoulou, Dimitrios Vlachakis, Elias Eliopoulos and Louis Papageorgiou
J. Clin. Med. 2025, 14(11), 3677; https://doi.org/10.3390/jcm14113677 - 23 May 2025
Cited by 1 | Viewed by 2557
Abstract
Background: Ankylosing Spondylitis (AS) is a rare autoinflammatory disorder affecting 0.1–1.4% of the population, with increasing recognition over the past 20 years. Although the specific causes of AS remain unclear, the presence of the HLA-B27 gene is associated with increased risk, though [...] Read more.
Background: Ankylosing Spondylitis (AS) is a rare autoinflammatory disorder affecting 0.1–1.4% of the population, with increasing recognition over the past 20 years. Although the specific causes of AS remain unclear, the presence of the HLA-B27 gene is associated with increased risk, though only 1–5% of carriers develop the disease. Despite extensive research, no definitive lab tests exist, and many patients are diagnosed years after symptom onset. Methods: In the present study, in order to investigate the disease’s genetic background in correlation with autoimmune diseases, a metanalysis has been performed following PRISMA guidelines using Scopus and PubMed publications towards extracting single-nucleotide polymorphisms (SNPs) of high importance for the disease. Moreover, the polymorphisms have been annotated and analyzed using information from several databases, including PubMed, LitVar2, ClinVar, and Gene Ontology. Results: From 1940 screened titles and abstracts, 57,909 studies were selected, with 539 meeting the inclusion criteria. The genetic background of AS is described through 794 genetic variants, of which 76 SNPs are directly associated with AS (Classes A and B), predominantly located in intronic regions. ERAP1 and IL23R emerged as key genes implicated in AS, while chromosomes 1, 2, and 5 accumulated the most associated SNPs. Functional enrichment revealed strong associations with immune regulation and interleukin signaling pathways, particularly IL6 and IL10 signaling. IL-6 promotes inflammation in AS, while IL-10 tries to suppress it, acting as an anti-inflammatory cytokine. Of the 78 AS-related SNPs, 16 were unique to AS, while 66 were common to autoimmune diseases, especially rheumatoid arthritis (RA) and psoriasis (PsO), suggesting genetic overlap between these diseases. Conclusions: This study creates a comprehensive genetic map of AS-associated SNPs, highlighting key pathways and genetic overlap with autoimmune diseases. These findings contribute to understanding disease mechanisms and could guide therapeutic interventions, advancing precision medicine in AS management. Full article
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19 pages, 2423 KiB  
Review
The Role of Diet in Modulating Inflammation and Oxidative Stress in Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis
by Daria Kupczyk, Rafał Bilski, Łukasz Szeleszczuk, Katarzyna Mądra-Gackowska and Renata Studzińska
Nutrients 2025, 17(9), 1603; https://doi.org/10.3390/nu17091603 - 7 May 2025
Cited by 2 | Viewed by 2833
Abstract
Rheumatic diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are chronic autoimmune disorders characterized by persistent inflammation and oxidative stress, leading to joint damage and reduced quality of life. In recent years, increasing attention has been given to [...] Read more.
Rheumatic diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are chronic autoimmune disorders characterized by persistent inflammation and oxidative stress, leading to joint damage and reduced quality of life. In recent years, increasing attention has been given to diet as a modifiable environmental factor that can complement pharmacological therapy. This review summarizes current evidence on how key dietary components—such as omega-3 fatty acids, fiber, polyphenols, and antioxidant vitamins—affect inflammatory pathways and oxidative balance. Special emphasis is placed on the Mediterranean diet, low-starch diets, and hypocaloric regimens, which have shown potential in improving disease activity. The gut microbiota emerges as a critical mediator between diet and immune function, with dietary interventions capable of restoring eubiosis and strengthening the intestinal barrier. Additionally, this paper discusses challenges in the clinical implementation of diet therapy, the need for personalized nutritional strategies, and the importance of integrating diet into holistic patient care. Collectively, findings suggest that dietary interventions may reduce disease activity, mitigate systemic inflammation, and enhance patients’ overall well-being. Full article
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18 pages, 3036 KiB  
Article
Guselkumab in Psoriatic Arthritis: Therapeutic Impact on Axial and Peripheral Involvement—Monocentric Real-World Evidence
by Roberta Foti, Giorgio Amato, Elisa Visalli, Ylenia Dal Bosco, Francesco De Lucia, Angelo Montana, Giambattista Privitera, Placido Romeo, Fabio Aiello, Maria Gabriella Paolì and Rosario Foti
J. Clin. Med. 2025, 14(9), 3151; https://doi.org/10.3390/jcm14093151 - 1 May 2025
Viewed by 1244
Abstract
Background: Axial involvement in psoriatic arthritis (axPsA) presents clinical and radiological differences from ankylosing spondylitis (AS), which may influence the therapeutic response. While Guselkumab has demonstrated efficacy in peripheral PsA, its role in axPsA is less well established, particularly in real-world settings. Objective: [...] Read more.
Background: Axial involvement in psoriatic arthritis (axPsA) presents clinical and radiological differences from ankylosing spondylitis (AS), which may influence the therapeutic response. While Guselkumab has demonstrated efficacy in peripheral PsA, its role in axPsA is less well established, particularly in real-world settings. Objective: To evaluate the positive effects of Guselkumab therapy in patients with psoriatic arthritis (PsA), 58.6% of whom have axial involvement, in a 12-month, single-center, longitudinal, prospective observational cohort study conducted in a real-life setting. Methods: A cohort of 99 patients with PsA, including 58 with axial involvement (axPsA), was treated with Guselkumab for 12 months. Treatment efficacy was assessed by evaluating the reduction in mBASDAI, ASDAS, DAPSA, VAS Pain, LEI, and HAQ scores. The Friedman test was used to analyze whether the overall changes from baseline to 12 months were statistically significant. Patients with axial involvement were assessed by MRI, with scores measured at baseline (t0), after 6 months (t6), and after 12 months (t12) of therapy. Statistical evaluation was conducted using the Friedman test, followed by pairwise comparisons of values obtained at different follow-up time points using the Wilcoxon signed-rank test. Additionally, the drug’s retention rate was examined using a Kaplan–Meier curve. Results: After 12 months of therapy, a statistically significant reduction was observed in all clinimetric parameters. Patients with axial involvement were also evaluated by MRI at baseline, after 6 months, and after 12 months of therapy. MRI images showed a reduction in bone marrow edema and a decrease in signal intensity, indicating a significant reduction in inflammation and confirming the drug’s efficacy. Retention rate values demonstrate that Guselkumab is well tolerated and effective in the long term for the majority of patients. Conclusions: This 12-month real-world study of 99 PsA patients confirms the efficacy of Guselkumab in reducing disease activity in both peripheral and axial forms. The findings align with previous RWE and clinical trials (DISCOVER-1 and -2), supporting its clinical utility in PsA and axPsA, with high treatment retention. Full article
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15 pages, 3151 KiB  
Case Report
Expanding the Genetic Framework: Insights into Non-HLA-B27 Contributions to Axial Spondylarthritis
by Ruxandra-Elena Nagit, Ioana Bratoiu, Corina Cianga, Mariana Pavel-Tanasa, Elena Rezus and Petru Cianga
Medicina 2025, 61(5), 793; https://doi.org/10.3390/medicina61050793 - 25 Apr 2025
Viewed by 712
Abstract
Background and Objectives: Spondylarthritis is a complex group of inflammatory diseases closely associated with the HLA-B27 antigen. However, the role of non-HLA-B27 alleles in the disease’s pathogenesis has gained significant scholarly attention in recent years. Case presentation: This case study presents a [...] Read more.
Background and Objectives: Spondylarthritis is a complex group of inflammatory diseases closely associated with the HLA-B27 antigen. However, the role of non-HLA-B27 alleles in the disease’s pathogenesis has gained significant scholarly attention in recent years. Case presentation: This case study presents a 49-year-old male with a history of progressive inflammatory back pain, characterized by morning stiffness and restricted spinal mobility developed over several years. Initially presenting with non-specific symptoms, the patient eventually experienced persistent axial pain and deteriorating functional limitations, which required further evaluation. Radiographic imaging supported the diagnosis of ankylosing spondylitis (AS) by identifying bilateral sacroiliitis. HLA genotyping revealed a negative result for HLA-B27 but positive results for HLA-B13 and HLA-B37. This finding serves as a foundation for exploring alternative genetic factors contributing to spondylarthritis (SpA). HLA-B13 and HLA-B37 exhibit structural and functional similarities to HLA-B27, particularly in their peptide-binding grooves. This resemblance may lead to overlapping peptide repertoires and increased T cell cross-reactivity. Moreover, these alleles belong to overlapping cross-reactive groups (CREGs) and share the Bw4 epitope. This suggests that they may contribute to disease pathogenesis via similar mechanisms, such as molecular mimicry and the dysregulation of natural killer (NK) cell interactions, as observed in HLA-B27. Conclusions: This case emphasizes the necessity of expanding diagnostic criteria to incorporate non-HLA-B27 markers, particularly for patients who are HLA-B27-negative. Enhancing our understanding of the roles of alternative genetic markers can improve diagnostic accuracy, enable personalized treatment approaches, and enhance outcomes for the diverse SpA patient population. Full article
(This article belongs to the Special Issue Autoimmune Diseases: Advances and Challenges)
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14 pages, 1144 KiB  
Review
MMP3 as a Molecular Link: Unraveling the Connection Between Ankylosing Spondylitis and Acute Coronary Syndrome
by Iliannis Y. Roa-Bruzón, Luis F. Duany-Almira, Yeminia M. Valle-Delgadillo, Héctor E. Flores-Salinas, Emmanuel Valdés-Alvarado and Jorge R. Padilla-Gutiérrez
Cells 2025, 14(8), 597; https://doi.org/10.3390/cells14080597 - 15 Apr 2025
Viewed by 803
Abstract
Ankylosing spondylitis (AS) is a chronic inflammatory disease that primarily affects the joints, limiting patients’ mobility and quality of life. Recent studies have shown that patients with AS have a significantly higher risk of developing severe cardiovascular complications, such as acute coronary syndrome [...] Read more.
Ankylosing spondylitis (AS) is a chronic inflammatory disease that primarily affects the joints, limiting patients’ mobility and quality of life. Recent studies have shown that patients with AS have a significantly higher risk of developing severe cardiovascular complications, such as acute coronary syndrome (ACS). A comprehensive review (2014–2024) included a study evaluating the significance of matrix metalloproteinase 3 (MMP-3) in cardiovascular risk among AS patients. The findings indicate that chronic inflammation in AS not only damages the joints but also contributes to the progression of cardiovascular diseases. At the molecular level, MMP-3 is instrumental in degrading the extracellular matrix, leading to instability in the atherosclerotic plaques and increasing the risk of ACS. Additionally, MMP-3 activation is related to the inflammatory pathways, such as tumor necrosis factor-alpha (TNF-α) and NF-κB, which amplify its effect on both joint destruction and vascular damage. This molecular approach offers new perspectives for understanding and treating AS and its cardiovascular complications, suggesting that MMP-3 inhibition could be a promising therapeutic strategy to mitigate cardiovascular risk in these patients. Full article
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14 pages, 1130 KiB  
Review
Cardio-Rheumatic Diseases: Inflammasomes Behaving Badly
by Farah Issa, Marah Abdulla, Faizah D. Retnowati, Huda Al-Khawaga, Hanin Alhiraky, Khalid M. Al-Harbi, Amal Al-Haidose, Zaid H. Maayah and Atiyeh M. Abdallah
Int. J. Mol. Sci. 2025, 26(8), 3520; https://doi.org/10.3390/ijms26083520 - 9 Apr 2025
Viewed by 701
Abstract
Cardio-rheumatology is an evolving and interdisciplinary field lying at the intersection of rheumatology and cardiovascular medicine that recognizes that individuals with autoimmune and inflammatory rheumatic complications have a much higher likelihood of developing cardiovascular diseases (CVDs). Inflammasomes are multiprotein complexes stimulated by the [...] Read more.
Cardio-rheumatology is an evolving and interdisciplinary field lying at the intersection of rheumatology and cardiovascular medicine that recognizes that individuals with autoimmune and inflammatory rheumatic complications have a much higher likelihood of developing cardiovascular diseases (CVDs). Inflammasomes are multiprotein complexes stimulated by the immune system after the detection of pathogens or cellular injury. Inflammasomes undergo a two-stage activation process initiated by nuclear factor (NF)-κB, subsequently playing a crucial role in innate immunity through activation of caspase 1 and the consequent release of proinflammatory cytokines such as IL-18 and IL-1β. However, a loss of control of inflammasome activation can cause inflammatory diseases in humans. Recent studies have focused on the role of inflammasomes in inflammatory cascades implicated in the pathogenesis of several diseases. Here, we review inflammasome activation, its mechanism of action, and its role in CVD. In particular, we describe the role of inflammasomes in rheumatic heart disease, Kawasaki disease, familial Mediterranean fever, ankylosing spondylitis, and rheumatoid arthritis as exemplars to illustrate pathobiological mechanisms and the potential for targeting inflammasomes for therapeutic benefit. Full article
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13 pages, 586 KiB  
Brief Report
Identification of Coronary Morphological Damage in Patients with Chronic Inflammatory Rheumatic Diseases
by Elena Heras-Recuero, Juan Antonio Martínez-López, Macarena Garbayo-Bugeda, Álvaro Castrillo-Capilla, Teresa Blázquez-Sánchez, Arantxa Torres-Roselló, Antia García-Fernández, Javier Llorca, Raquel Largo, Juan Antonio Franco-Peláez, José Tuñón and Miguel Ángel González-Gay
Diagnostics 2025, 15(7), 922; https://doi.org/10.3390/diagnostics15070922 - 2 Apr 2025
Viewed by 626
Abstract
Objective: Patients with chronic inflammatory rheumatic diseases (CIRDs) have a higher incidence of coronary artery disease (CAD) due to accelerated atherogenesis. This study aimed to assess the extent and location of CAD lesions in CIRD patients compared to non-CIRD patients. Methods: A retrospective [...] Read more.
Objective: Patients with chronic inflammatory rheumatic diseases (CIRDs) have a higher incidence of coronary artery disease (CAD) due to accelerated atherogenesis. This study aimed to assess the extent and location of CAD lesions in CIRD patients compared to non-CIRD patients. Methods: A retrospective study was conducted on CIRD patients (rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis) who underwent coronary angiography at Hospital Fundación Jiménez Díaz (Madrid, Spain) between 2018 and 2022. For each CIRD patient, at least two frequency-matched controls were selected based on sex, age (±2 years), diabetic status, and clinical indication for coronary angiography. The indications for coronary angiography in both groups were chronic coronary syndrome and acute coronary syndrome with or without ST elevation. Results: A total of 66 CIRD patients were included, with 42 (63.6%) women, and a median age of 66.6 years (range: 58.3–75.2). Compared to the controls, CIRD patients had a higher number of affected coronary arteries (2.03 vs. 1.56, p = 0.03). The mid-anterior descending artery and the right posterior descending artery were more frequently involved in CIRD patients than in controls (odds ratio [OR] of 2.45 and 3.53, respectively, p ≤ 0.02 for both comparisons). The frequency of coronary calcification was higher in CIRD patients, though the difference did not reach statistical significance (5 of 66 in CIRD patients vs. 3 of 140 in non-CIRD controls, OR of 3.74, p = 0.06). Revascularization was more commonly performed in patients with CIRD (50 of 66 vs. 85 of 140 in those without CIRD (OR: 2.02 [95% CI: 1.01–4.18]; p = 0.03). Conclusions: Patients with CIRD exhibit more extensive CAD, with a higher propensity for involvement inthe mid-anterior descending and right posterior descending arteries compared to patients without CIRD. These findings highlight the need for closer cardiovascular monitoring and early risk stratification in CIRD patients to improve the detection and management of CAD. Full article
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Article
Proteomic Profiling of Inflammatory Protein Dysregulation in HLA-B27-Positive Ankylosing Spondylitis: Molecular Signatures and Potential Biomarkers
by Yuzhu Yan, Jihan Wang, Yangyang Wang, Junye Liu, Wenjuan Yang, Min Niu, Yan Yu and Heping Zhao
Biomolecules 2025, 15(4), 516; https://doi.org/10.3390/biom15040516 - 1 Apr 2025
Viewed by 751
Abstract
This study explored the proteomic landscape of inflammatory protein dysregulation in ankylosing spondylitis (AS), a chronic inflammatory disorder primarily affecting the axial skeleton and strongly associated with the HLA-B27 allele, particularly the HLA-B2705 and HLA-B2704 subtypes prevalent in Chinese populations. Blood samples from [...] Read more.
This study explored the proteomic landscape of inflammatory protein dysregulation in ankylosing spondylitis (AS), a chronic inflammatory disorder primarily affecting the axial skeleton and strongly associated with the HLA-B27 allele, particularly the HLA-B2705 and HLA-B2704 subtypes prevalent in Chinese populations. Blood samples from HLA-B27-positive AS patients and normal controls (NC) were analyzed using the Olink Target 96 inflammation panel to profile 92 inflammatory proteins. HLA-B27 subtyping was performed via PCR-SSP. To identify key proteins and stratify AS subtypes, we employed machine learning classifiers, including LightGBM models coupled with SHAP value interpretation, alongside traditional statistical analyses. The proteomic analysis revealed significant dysregulation of pro-inflammatory cytokines, such as IL-6 and IL-17A, in AS patients compared to NC, with CXCL9 and NRTN identified as potential biomarkers associated with disease activity. The combination of LightGBM classifiers and traditional statistical methods demonstrated high accuracy in distinguishing AS from NC and effectively stratifying subtypes. These findings provide valuable insights into the inflammatory mechanisms underlying AS pathogenesis and highlight potential biomarkers and therapeutic targets for improving diagnosis and treatment strategies. Future studies with larger and more diverse cohorts, as well as longitudinal designs, are warranted to validate these biomarkers and elucidate their dynamic changes during disease progression. Full article
(This article belongs to the Collection Feature Papers in 'Biomacromolecules: Proteins')
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