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RMD Open Jun 2024The International Map of Axial Spondyloarthritis (IMAS) is a global initiative aimed to assess the impact and burden of axial spondyloarthritis (axSpA) and identify the...
BACKGROUND
The International Map of Axial Spondyloarthritis (IMAS) is a global initiative aimed to assess the impact and burden of axial spondyloarthritis (axSpA) and identify the unmet needs from the patient's perspective.
METHOD
IMAS is a collaboration between the Axial Spondyloarthritis International Federation (ASIF), the University of Seville, Novartis Pharma AG and steered by a scientific committee. IMAS collected information through an online cross-sectional survey (2017-2022) from unselected patients with axSpA from Europe, Asia, North America, Latin America and Africa who completed a comprehensive questionnaire containing over 120 items.
RESULTS
5557 patients with axSpA participated in IMAS. Mean age was 43.9 ±12.8 years, 55.4% were female, 46.2% had a university education and 51.0% were employed. The mean diagnostic delay was 7.4 ±9.0 years (median: 4.0), and the mean symptom duration was 17.1 ±13.3 years. 75.0% of patients had active disease (Bath Ankylosing Spondylitis Disease Activity Index ≥4), and 59.4% reported poor mental health (12-item General Health Questionnaire ≥3). In the year before the survey, patients had visited primary care physicians 4.6 times and the rheumatologist 3.6 times. 78.6% had taken non-steroidal anti-inflammatory drug ever, 48.8% biological disease-modifying antirheumatic drugs and 43.6% conventional synthetic disease-modifying antirheumatic drugs. Patients's greatest fear was disease progression (55.9%), while the greatest hope was to be able to relieve pain (54.2%).
CONCLUSIONS
IMAS shows the global profile of patients with axSpA, highlighting unmet needs, lengthy delays in diagnosis and high burden of disease in patients with axSpA worldwide. This global information will enable more detailed investigations to obtain evidence on the critical issues that matter to patients around the world to improve their care and quality of life.
Topics: Humans; Male; Female; Adult; Cross-Sectional Studies; Middle Aged; Axial Spondyloarthritis; Quality of Life; Surveys and Questionnaires; Cost of Illness; Global Health; Severity of Illness Index
PubMed: 38851236
DOI: 10.1136/rmdopen-2023-003504 -
Frontiers in Immunology 2024Currently, there is a lack of an objective quantitative measure to comprehensively evaluate the inflammatory activity of axSpA, which poses certain challenges in...
BACKGROUND
Currently, there is a lack of an objective quantitative measure to comprehensively evaluate the inflammatory activity of axSpA, which poses certain challenges in accurately assessing the disease activity.
OBJECTIVE
To explore the value of combined-parameter models of sacroiliac joints (SIJs) MRI relaxometry and peripheral blood Mucosal-associated invariant T (MAIT) cells in evaluating the inflammatory activity of axial spondyloarthritis (axSpA).
METHODS
This retrospective clinical study included 88 axSpA patients (median age 31.0 (22.0, 41.8) years, 21.6% females) and 20 controls (median age 28.0 (20.5, 49.5) years, 40.0% females). The axSpA group was classified into active subgroup (n=50) and inactive subgroup (n=38) based on ASDAS-CRP. All participants underwent SIJs MRI examination including T1 and T2* mapping, and peripheral blood flow cytometry analysis of MAIT cells (defined as CD3Vα7.2CD161) and their activation markers (CD69). The T1 and T2* values, as were the percentages of MAIT cells and CD69MAIT cells were compared between different groups. Combined-parameter models were established using logistic regression, and ROC curves were employed to evaluate the diagnostic efficacy.
RESULTS
The T1 values of SIJs and %CD69MAIT cells in the axSpA group and its subgroup were higher than the control group (p<0.05), while %MAIT cells were lower than the control group (p<0.05). The T1 values and %CD69MAIT cells correlated positively, while %MAIT cells correlated negatively, with the ASDAS-CRP (r=0.555, 0.524, -0.357, p<0.001). Between the control and axSpA groups, and between the inactive and active subgroups, the combined-parameter model T1 mapping+%CD69MAIT cells has the best efficacy (AUC=0.959, 0.879, sensibility=88.6, 70%, specificity=95.0, 94.7%, respectively).
CONCLUSION
The combined-parameter model T1 mapping+%CD69MAIT cells allows a more accurate evaluation of the level of inflammatory activity.
Topics: Humans; Female; Mucosal-Associated Invariant T Cells; Male; Adult; Magnetic Resonance Imaging; Axial Spondyloarthritis; Retrospective Studies; Middle Aged; Young Adult; Sacroiliac Joint; Inflammation; Biomarkers
PubMed: 38840918
DOI: 10.3389/fimmu.2024.1391280 -
Genetic associations in ankylosing spondylitis: circulating proteins as drug targets and biomarkers.Frontiers in Immunology 2024Ankylosing spondylitis (AS) is a complex condition with a significant genetic component. This study explored circulating proteins as potential genetic drug targets or...
BACKGROUND
Ankylosing spondylitis (AS) is a complex condition with a significant genetic component. This study explored circulating proteins as potential genetic drug targets or biomarkers to prevent AS, addressing the need for innovative and safe treatments.
METHODS
We analyzed extensive data from protein quantitative trait loci (pQTLs) with up to 1,949 instrumental variables (IVs) and selected the top single-nucleotide polymorphism (SNP) associated with AS risk. Utilizing a two-sample Mendelian randomization (MR) approach, we assessed the causal relationships between identified proteins and AS risk. Colocalization analysis, functional enrichment, and construction of protein-protein interaction networks further supported these findings. We utilized phenome-wide MR (phenMR) analysis for broader validation and repurposing of drugs targeting these proteins. The Drug-Gene Interaction database (DGIdb) was employed to corroborate drug associations with potential therapeutic targets. Additionally, molecular docking (MD) techniques were applied to evaluate the interaction between target protein and four potential AS drugs identified from the DGIdb.
RESULTS
Our analysis identified 1,654 plasma proteins linked to AS, with 868 up-regulated and 786 down-regulated. 18 proteins (AGER, AIF1, ATF6B, C4A, CFB, CLIC1, COL11A2, ERAP1, HLA-DQA2, HSPA1L, IL23R, LILRB3, MAPK14, MICA, MICB, MPIG6B, TNXB, and VARS1) that show promise as therapeutic targets for AS or biomarkers, especially MAPK14, supported by evidence of colocalization. PhenMR analysis linked these proteins to AS and other diseases, while DGIdb analysis identified potential drugs related to MAPK14. MD analysis indicated strong binding affinities between MAPK14 and four potential AS drugs, suggesting effective target-drug interactions.
CONCLUSION
This study underscores the utility of MR analysis in AS research for identifying biomarkers and therapeutic drug targets. The involvement of Th17 cell differentiation-related proteins in AS pathogenesis is particularly notable. Clinical validation and further investigation are essential for future applications.
Topics: Spondylitis, Ankylosing; Humans; Biomarkers; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Protein Interaction Maps; Genetic Predisposition to Disease; Blood Proteins; Mendelian Randomization Analysis; Molecular Docking Simulation; Genome-Wide Association Study
PubMed: 38835753
DOI: 10.3389/fimmu.2024.1394438 -
Arthritis Research & Therapy Jun 2024Immune checkpoints have emerged as promising therapeutic targets for autoimmune diseases. However, the specific roles of immune checkpoints in the pathophysiology of...
Exploration of the combined role of immune checkpoints and immune cells in the diagnosis and treatment of ankylosing spondylitis: a preliminary study immune checkpoints in ankylosing spondylitis.
OBJECTIVE
Immune checkpoints have emerged as promising therapeutic targets for autoimmune diseases. However, the specific roles of immune checkpoints in the pathophysiology of ankylosing spondylitis (AS) remain unclear.
METHODS
Hip ligament samples were obtained from two patient groups: those with AS and femoral head deformity, and those with femoral head necrosis but without AS, undergoing hip arthroplasty. Label-Free Quantification (LFQ) Protein Park Analysis was used to identify the protein composition of the ligaments. Peripheral blood samples of 104 AS patients from public database were used to validate the expression of key proteins. KEGG, GO, and GSVA were employed to explore potential pathways regulated by immune checkpoints in AS progression. xCell was used to calculate cell infiltration levels, LASSO regression was applied to select key cells, and the correlation between immune checkpoints and immune cells was analyzed. Drug sensitivity analysis was conducted to identify potential therapeutic drugs targeting immune checkpoints in AS. The expression of key genes was validated through immunohistochemistry (IHC).
RESULTS
HLA-DMB and HLA-DPA1 were downregulated in the ligaments of AS and this has been validated through peripheral blood datasets and IHC. Significant differences in expression were observed in CD8 + Tcm, CD8 + T cells, CD8 + Tem, osteoblasts, Th1 cells, and CD8 + naive T cells in AS. The infiltration levels of CD8 + Tcm and CD8 + naive T cells were significantly positively correlated with the expression levels of HLA-DMB and HLA-DPA1. Immune cell selection using LASSO regression showed good predictive ability for AS, with AUC values of 0.98, 0.81, and 0.75 for the three prediction models, respectively. Furthermore, this study found that HLA-DMB and HLA-DPA1 are involved in Th17 cell differentiation, and both Th17 cell differentiation and the NF-kappa B signaling pathway are activated in the AS group. Drug sensitivity analysis showed that AS patients are more sensitive to drugs such as doramapimod and GSK269962A.
CONCLUSION
Immune checkpoints and immune cells could serve as avenues for exploring diagnostic and therapeutic strategies for AS.
Topics: Humans; Spondylitis, Ankylosing; Male; Female; Adult; Middle Aged; Immune Checkpoint Proteins
PubMed: 38835033
DOI: 10.1186/s13075-024-03341-6 -
RMD Open Jun 2024To assess the impact of bimekizumab on physical functioning, sleep, work productivity and overall health-related quality of life (HRQoL) in patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
Improved physical functioning, sleep, work productivity and overall health-related quality of life with bimekizumab in patients with axial spondyloarthritis: results from two phase 3 studies.
OBJECTIVE
To assess the impact of bimekizumab on physical functioning, sleep, work productivity and overall health-related quality of life (HRQoL) in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) in the phase 3 studies BE MOBILE 1 and 2.
METHODS
Patients were randomised to subcutaneous bimekizumab 160 mg or placebo every 4 weeks; from Week 16, all patients received bimekizumab 160 mg every 4 weeks. We report the following outcomes to Week 52: Bath Ankylosing Spondylitis Functional Index (BASFI), Medical Outcomes Study Sleep Scale Revised (MOS-Sleep-R) Index II, Work Productivity and Activity Impairment: axSpA (WPAI:axSpA), Short Form-36 Physical and Mental Component Summary (SF-36 PCS/MCS) and Ankylosing Spondylitis Quality of Life (ASQoL).
RESULTS
At Week 16, bimekizumab-randomised patients demonstrated significantly greater improvement from baseline versus placebo in BASFI, SF-36 PCS and ASQoL (p<0.001), and numerically greater improvements in MOS-Sleep-R Index II and WPAI:axSpA scores. Higher proportions of bimekizumab-randomised versus placebo-randomised patients at Week 16 achieved increasingly stringent thresholds for improvements in BASFI (0 to ≤4), and thresholds for meaningful improvements in SF-36 PCS (≥5-point increase from baseline) and ASQoL (≥4-point decrease from baseline). Responses were sustained or further improved to Week 52, where 60%-70% of bimekizumab-treated patients achieved BASFI ≤4 and meaningful improvements in SF-36 PCS and ASQoL, regardless of whether originally randomised to bimekizumab or placebo.
CONCLUSION
Bimekizumab treatment led to early improvements in physical function, sleep, work productivity and overall HRQoL at Week 16 in patients across the full axSpA disease spectrum. Improvements were sustained to Week 52.
TRIAL REGISTRATION NUMBERS
NCT03928704; NCT03928743.
Topics: Humans; Quality of Life; Male; Female; Adult; Middle Aged; Sleep; Treatment Outcome; Axial Spondyloarthritis; Severity of Illness Index; Physical Functional Performance; Double-Blind Method; Efficiency; Antibodies, Monoclonal, Humanized
PubMed: 38834351
DOI: 10.1136/rmdopen-2024-004202 -
Cureus May 2024Mandibular condyle aplasia and temporomandibular joint (TMJ) ankylosis represent complex challenges in diagnosis and management, affecting jaw function and facial...
Mandibular condyle aplasia and temporomandibular joint (TMJ) ankylosis represent complex challenges in diagnosis and management, affecting jaw function and facial aesthetics. This case report presents a five-year-old female child with a right-sided small jaw and facial asymmetry due to left-sided TMJ ankylosis. The coexistence of mandibular condyle aplasia and TMJ ankylosis underscores the need for comprehensive evaluation and tailored treatment approaches. Syndromic associations, such as Goldenhar syndrome and Treacher Collins syndrome, further complicate diagnosis and management. Surgical intervention involving left-side gap arthroplasty and reconstruction using a costochondral graft/temporalis fascia was performed under general anesthesia. However, postoperative complications, including decreased mouth opening and left-sided lower motor neuron facial palsy, necessitated further surgical debridement and drainage of an abscess. The case emphasizes the importance of a multidisciplinary approach in addressing complex craniofacial anomalies, with treatment strategies such as bone grafting and tailored surgical interventions offering promising outcomes. Understanding the multifaceted etiology of mandibular condyle aplasia and TMJ ankylosis is crucial for optimal management, highlighting the collaborative efforts required for achieving favorable patient outcomes.
PubMed: 38832193
DOI: 10.7759/cureus.59615 -
Scientific Reports Jun 2024To explore the role of YAP, a key effector of the Hippo pathway, in temporomandibular joint (TMJ) ankylosis. The temporal and spatial expression of YAP was detected via...
To explore the role of YAP, a key effector of the Hippo pathway, in temporomandibular joint (TMJ) ankylosis. The temporal and spatial expression of YAP was detected via immunohistochemistry and multiplex immunohistochemistry on postoperative Days 1, 4, 7, 9, 11, 14 and 28 in a sheep model. Isolated mesenchymal stem cells (MSCs) from samples of the Day 14. The relative mRNA expression of YAP was examined before and after the osteogenic induction of MSCs. A YAP-silenced MSC model was constructed, and the effect of YAP knockdown on MSC function was examined. YAP is expressed in the nucleus of the key sites that determine the ankylosis formation, indicating that YAP is activated in a physiological state. The expression of YAP increased gradually over time. Moreover, the number of cells coexpressing of RUNX2 and YAP-with the osteogenic active zone labelled by RUNX2-tended to increase after Day 9. After the osteogenic induction of MSCs, the expression of YAP increased. After silencing YAP, the osteogenic, proliferative and migratory abilities of the MSCs were inhibited. YAP is involved in the early development of TMJ bony ankylosis. Inhibition of YAP using shRNA might be a promising way to prevent or treat TMJ ankylosis.
Topics: Animals; Mesenchymal Stem Cells; Temporomandibular Joint Disorders; Ankylosis; Osteogenesis; YAP-Signaling Proteins; Temporomandibular Joint; Sheep; Cell Proliferation; Disease Models, Animal; Cell Differentiation; Adaptor Proteins, Signal Transducing; Core Binding Factor Alpha 1 Subunit; Cell Movement; Transcription Factors
PubMed: 38830996
DOI: 10.1038/s41598-024-63613-8 -
The Journal of Craniofacial Surgery Jun 2024Temporomandibular joint ankylosis (TMJA) secondary to congenital infiltrating lipomatosis of the face (CILF) is an exceptionally uncommon condition which is...
Temporomandibular joint ankylosis (TMJA) secondary to congenital infiltrating lipomatosis of the face (CILF) is an exceptionally uncommon condition which is characterized by the involvement of unilateral facial soft tissues and bones. In some cases, the extensive exophytic bony growth in the temporomandibular joint region often extends toward the skull base and lies near adjacent vital structures. Only very few cases of TMJA associated with CILF have been reported in the literature. The authors report a case of a 36-year-old female with right TMJA secondary to CILF. The bony overgrowth in the right temporomandibular joint region was arising from a deformed right mandibular condyle, extending towards the ipsilateral temporal bone, greater wing of the sphenoid, skull base, and approaching the lateral limit of foramen ovale, and foramen spinosum. To prevent any damage to the skull base and adjacent vital structures and to achieve adequate mouth opening, the authors have performed a unique technique of subankylotic osteotomy for the release of TMJA, instead of conventional gap arthroplasty.
PubMed: 38830084
DOI: 10.1097/SCS.0000000000010355 -
Terapevticheskii Arkhiv Jun 2024Spondyloarthritis (SpA) is a group of rheumatic diseases that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA) and a number of other diseases. SpA lead to... (Review)
Review
Spondyloarthritis (SpA) is a group of rheumatic diseases that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA) and a number of other diseases. SpA lead to a significant social problem, since it is a common pathology that debuts mainly at a young age, significantly impairing the ability to work and the ability to social contacts of the most active part of the population. For all the main types of chronic progressive SpA, biological agents (biologics) are of great importance in patients with persistent activity despite standard treatment, especially in the case of predominantly axial involvement, since in this case it is actually the only option for effective treatment, in addition to the constant use of non-steroidal anti-inflammatory drugs (NSAIDs). Over the past decade, interleukin-17A (IL-17A) inhibitors have taken the first place in therapy of SpA, because, according to modern ideas about pathogenesis, IL-17A may be a key target for therapeutic intervention in SpA. In terms of ensuring availability for Russian patients with SpA, it is of particular importance to the introduction of the original medication from the group of IL-17A inhibitors Netakimab (NTK). This review presents data from randomized clinical trials of NTK phases I, II and III in AS and PsA also post-registration observational studies of phase IV, including analysis of subpopulations of patients of special interest, in particular, patients with psoriatic spondylitis. NTK demonstrated high effectiveness in the treatment of SpA both in randomized clinical trials and in clinical practice. The drug is characterized by a rapid onset of clinical action and persistent maintenance of the achieved improvement, a complex effect on various manifestations of the disease, is able to have a structure-modifying effect and slow down the progression of both the erosive process and osteoproliferation. The safety profile of NTK is generally typical for the entire group of IL-17 inhibitors. The drug has low immunogenicity, which allows us to count on the possibility of many years of effective use. Resolutions of expert councils on the use of NTK in AS and PsA support the inclusion of this drug in clinical guidelines.
Topics: Humans; Interleukin-17; Spondylarthritis; Antibodies, Monoclonal, Humanized; Treatment Outcome; Spondylitis, Ankylosing
PubMed: 38829817
DOI: 10.26442/00403660.2024.05.202794 -
Terapevticheskii Arkhiv Jun 2024To study the frequency of hypogonadism (HG) in men with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and to evaluate the impact...
AIM
To study the frequency of hypogonadism (HG) in men with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and to evaluate the impact of HG on the course of RA and and concomitant diseases.
MATERIALS AND METHODS
A single-stage continuous study included 170 men with RA, 57 men with AS and 85 men with PsA, who were hospitalized at the Nasonova Research Institute of Rheumatology. Patients were assessed for total testosterone (ТS) levels and subsequently divided into subgroups with normal (>12 nmol/l) and reduced levels. An intergroup comparison was carried out on the main indicators used in clinical rheumatological practice to assess the stage, activity and other medical and demographic characteristics of rheumatic disease, as well as on concomitant conditions. The second stage of the study involved a pairwise intergroup comparison among patients with HG with RA, AS and PsA.
RESULTS
The incidence of ТS deficiency among patients with RA was 24.1%, among patients with AS - 17.5%, and with PsA - 31.8%. In patients with RA, HG was associated with a significantly higher mean body mass index, higher fasting blood glucose and uric acid, higher erythrocyte sedimentation rate and anemia. Patients with AS with HG had significantly lower hemoglobin levels and more frequent anemia, as well as higher levels of C-reactive protein and erythrocyte sedimentation rate. In PsA, older age was observed in the androgen deficiency group, as well as higher body mass index and fasting glucose levels; obesity was more common. An intergroup comparison of quantitative and qualitative indicators between patients with androgen deficiency in all three rheumatic diseases (RDs) did not reveal significant differences in the average concentrations of ТS, luteinizing hormone, sex hormone binding globulin, experience of RD, laboratory markers of inflammatory activity, as well as glucose and uric acid. A similar incidence of diabetes mellitus, obesity and anemia was noted for all three nosologies.
CONCLUSION
ТS levels and the presence of HG were not associated with the stage and activity of RD, but ТS deficiency was accompanied by higher laboratory indicators of inflammatory activity, lower hemoglobin values, and metabolic disorders. Patients with HG, regardless of nosology, had similar levels of sex hormones and indicators reflecting RD and concomitant conditions.
Topics: Humans; Male; Hypogonadism; Middle Aged; Testosterone; Arthritis, Psoriatic; Adult; Arthritis, Rheumatoid; Spondylitis, Ankylosing; Russia; Incidence; Blood Sedimentation
PubMed: 38829810
DOI: 10.26442/00403660.2024.05.202704