Biomarkers In Arthritis Research Articles

One Step Visual Homogeneous Immunoassay of a Rheumatoid Arthritis Biomarker in Serum via Target-Regulated Steric Hindrance and Competitive Recognition.

Homogeneous analysis techniques offer several advantages as alternatives to heterogeneous immunoassays, such as simplicity and rapidity. In this study, a visual homogeneous immunoassay without a labeling process was developed based on target-induced steric hindrance to regulate competitive recognition mechanism. Specifically, as the analyte concentration varies, the change of microenvironment based on steric hindrance could affect the recognition of Cu2+ by signal probes. Herein, taking anticyclic citrullinated peptide antibody (anti-CCP) as an example, the method was verified. Cu2+ can bind to histidine (His), as well as signal probes. Cyclic citrullinated peptide containing His was served as the capture antigen, and the fluorescence of both CdTe quantum dots and calcein can be quenched by Cu2+. Then, this quenching effect can be regulated by the change of steric hindrance, so that anti-CCP analysis can be realized. The limit of detection of anti-CCP was as low as 0.002 and 0.01 U/mL in fluorescence mode and red, green, and blue (RGB) mode, respectively. Furthermore, clinical practicality was validated through 46 clinical samples, including rheumatoid arthritis patients (n = 28) and healthy donors (n = 18), with the assay demonstrating a sensitivity and specificity of 96.4% and 88.9%, respectively. Indeed, the results were consistent with those of clinical electrochemiluminescence immunoassays and digital radiography images. Overall, this method shows great potential for clinical application and offers a universal template for a label-free homogeneous immunoassay.

Temporal kinetics of serum amyloid A (SAA) concentration and identification of SAA isoforms in blood and synovial fluid of horses with experimentally induced septic arthritis, non-septic synovitis, and systemic inflammation.

Prompt diagnosis of equine septic arthritis is crucial for successful treatment. Serum amyloid A (SAA) has been suggested as a reliable biomarker. However, we previously found that synovial fluid SAA increases in nonaffected joints of horses with septic arthritis. We hypothesized that systemic SAA may leak into the nonaffected joints. If this is the case, we also hypothesized that locally produced joint SAA isoforms may be better candidates for septic arthritis biomarkers. Thus, our objectives were 1) to evaluate the temporal kinetics of systemic and synovial fluid SAA in horses with septic arthritis (n = 5), non-septic synovitis (n = 5), and systemic inflammation (n = 5), examining both affected and contralateral joints; and 2) investigate putative locally produced joint SAA isoforms and detect amino-acid differences between them. We confirmed that SAA increases significantly in synovial fluid in nonaffected joints of horses with systemic inflammation (≤352 mg/L), as well as in contralateral nonaffected joins in horses with septic arthritis (≤1,830 mg/L) compared to baseline at time 0 (<0.2 mg/L). We also identified a putative locally produced joint SAA peptide in synovial fluid (FGDSGHGAADSR) that differed in 1 amino acid from 2 systemic peptides found both in plasma and synovial fluid. The putative joint SAA isoform was present in joints of horses with both septic arthritis and systemic inflammation (ion intensities 104-106). Thus, the increase of synovial fluid SAA may be both due to the leakage of SAA from serum into joints and local production of joint SAA isoforms.

Genomic and Serological Rheumatoid Arthritis Biomarkers, MUC5B Promoter Variant, and Interstitial Lung Abnormalities.

Rheumatoid arthritis (RA) has been implicated in interstitial lung disease (ILD) as majority of studies have been comprised of patients with known RA. However, it remains unclear whether an underlying risk for RA in combination with genetic risk for pulmonary fibrosis is associated with radiological markers of early lung injury and fibrosis in broader population samples. Determine whether genetic and serological biomarkers of RA risk in combination with the MUC5B (rs35705950) risk allele (T) are associated with interstitial lung abnormalities (ILA) on computed tomography (CT) scans. Associations of RA-risk HLA-DRB1 alleles (*04:01, *04:08, *04:05, *04:04, *10:01) and serum RA autoantibodies with ILA in the Multi-Ethnic Study of Atherosclerosis (MESA, n=4,018) and COPDGene (n=5,963) cohorts were modeled using logistic regression and adjusted for age, sex, self-reported race and ethnicity, smoking history, body mass index, and principal components of genetic ancestry. The prevalence of an RA risk HLA-DRB1 allele was 16.5% and 21.9% in MESA and COPDGene, respectively. ILA was present in 3.9% and 11% in MESA and COPDGene, respectively. An RA risk HLA-DRB1 allele was not significantly associated with ILA in MESA and COPDGene. In MESA, higher serum levels of IgA rheumatoid factor (RF) and anti-cyclic citrullinated peptide were associated with an odds ratio (OR) for ILA of 1.20 (95% CI 1.07-1.35) and 1.19 (95% CI 1.04-1.37), respectively. Among smokers without baseline ILA, per doubling of IgM RF was associated with an OR for ILA 10 years later of 1.25 (95% CI 1.08-1.43). Associations were not significantly different by MUC5B risk allele status. RA-related HLA-DRB1 alleles were not associated with ILA, whereas higher serum levels of IgM RF among smokers without baseline ILA were associated with subsequent ILA.

A-281 Comparison of C-reactive Protein, Procalcitonin, and Presepsin in Blood and Synovial Fluid as Diagnostic Biomarkers for Septic Arthritis

Abstract Background Early detection and prompt treatment are crucial for managing septic arthritis (SA). However, diagnosing SA at an early stage can be challenging since the symptoms are non-specific, and there is no definitive diagnostic test available. This study aimed to investigate the potential of biomarkers as a reliable diagnostic tool for SA. Methods A prospective study was conducted to collect residual blood and synovial fluid samples from patients who underwent blood sampling and arthrocentesis for differential diagnosis due to suspected SA. The collected samples were analyzed for C-reactive protein (CRP), procalcitonin, and presepsin. The data obtained from the analysis were subjected to statistical analysis. Results From January to November 2023, 58 patients were enrolled. They comprised 24 men and 34 women with a median age of 71.1 (interquartile range, IQR 64.0-79.3) years. Twenty-one patients were diagnosed with SA and 37 with non-SA, including osteoarthritis (n=2), osteonecrosis (n=1), meniscus tear (n=1), abscess (n=1), contusion (n=2), and mechanical complications of implants (n=30). There were no significant differences in age or sex distribution between the two groups. The median blood and synovial fluid CRP levels were 4.24 and 1.85 mg/dL, respectively, in the SA group and 0.24 and 0.11 in the non-SA group. The median blood and synovial fluid procalcitonin levels were 0.0383 and 0.0403 ng/mL in the SA group and 0.0358 and 0.0488 in the non-SA group. The median blood and synovial fluid presepsin levels were 307 and 1389 pg/mL in the SA group and 192 and 959 in the non-SA group. Except for blood procalcitonin, all showed statistically significant differences between the SA and non-SA groups. In the ROC curve analysis, blood CRP displayed the highest area under the curve (AUC) of 0.795 with a 0.47 mg/dL cut-off value, 90.5% sensitivity, and 64.9% specificity. Synovial fluid CRP displayed similar results of 0.786 AUC, 0.30 mg/dL cut-off value, 85.0% sensitivity, and 71.4% specificity. Blood and synovial fluid procalcitonin had low AUCs of 0.532 and 0.659, respectively, and were insufficient to differentiate between SA and NS groups. The AUC (0.696 vs. 0.704), sensitivity (76.2% vs. 76.2%), and specificity (67.6% vs. 62.2%) of blood and synovial fluid presepsin were similar; however, synovial fluid showed a significantly higher cut-off value, 4.5 times that of blood (237 pg/mL vs. 1087 pg/mL). Conclusions Procalcitonin was not a reliable marker for distinguishing between SA and non-SA, regardless of whether it was measured in blood or synovial fluids. However, CRP and presepsin proved useful markers when measured in either blood or synovial fluid. In particular, when measuring presepsin in synovial fluid, an optimal cut-off value is needed.

Digital biomarkers for psoriatic arthritis: a qualitative focus group study on patient-perceived opportunities and barriers

ObjectivesThe widespread adoption of wearables, for example, smartphones and smartwatches in the daily lives of the general population, allows passive monitoring of physiological and behavioural data in the real world....

Biomarkers in Psoriasis and Psoriatic Arthritis: Where Are We Now?

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual conference and trainee symposium, the status of psoriatic disease (PsD) biomarkers was discussed in a workshop. The significant heterogeneity of PsD causes disease management to be very challenging, but biomarkers can prove helpful in disease diagnosis, stratification, and precision medicine. Although a few potential biomarkers have been discovered, none have been fully validated. Recent studies have used omic technologies that show promise but need further verification and validation. Many challenges remain, but the anticipated results of studies being conducted by recently established large consortia may lead to the identification of clinically actionable biomarkers.

Synovial fluid extracellular vesicles as arthritis biomarkers: the added value of lipid-profiling and integrated omics.

Arthritis, a diverse group of inflammatory joint disorders, poses great challenges in early diagnosis and targeted treatment. Timely intervention is imperative, yet conventional diagnostic methods are not able to detect subtle early symptoms. Hence, there is an urgent need for specific biomarkers that discriminate between different arthritis forms and for early diagnosis. The pursuit of such precise diagnostic tools has prompted a growing interest in extracellular vesicles (EVs). EVs, released by cells in a regulated fashion, are detectable in body fluids, including synovial fluid (SF), which fills the joint space. They provide insights into the intricate molecular landscapes of arthritis, and this has stimulated the search for minimally invasive EV-based diagnostics. As such, the analysis of EVs in SF has become a focus for identifying EV-based biomarkers for joint disease endotyping, prognosis, and progression. EVs are composed of a lipid bilayer and a wide variety of different cargo types, of which proteins and RNAs are widely investigated. In contrast, membrane lipids of EVs, especially the abundance, presence, or absence of specific lipids and their contribution to the biological activity of EVs, are largely overlooked in EV research. Furthermore, the identification of specific combinations of different EV components acting in concert in EVs can fuel the definition of composite biomarkers. We here provide a state-of-the-art overview of the knowledge on SF-derived EVs with emphasis on lipid analysis and we give an example of the added value of integrated proteomics and lipidomics analysis in the search for composite EV-associated biomarkers.

High-throughput micro-CT analysis identifies sex-dependent biomarkers of erosive arthritis in TNF-Tg mice and differential response to anti-TNF therapy.

Development of reliable disease activity biomarkers is critical for diagnostics, prognostics, and novel drug development. Although computed tomography (CT) is the gold-standard for quantification of bone erosions, there are no consensus approaches or rationales for utilization of specific outcome measures of erosive arthritis in complex joints. In the case of preclinical models, such as sexually dimorphic tumor necrosis factor transgenic (TNF-Tg) mice, disease severity is routinely quantified in the ankle through manual segmentation of the talus or small regions of adjacent bones primarily due to the ease in measurement. Herein, we sought to determine the particular hindpaw bones that represent reliable biomarkers of sex-dependent disease progression to guide future investigation and analysis. Hindpaw micro-CT was performed on wild-type (n = 4 male, n = 4 female) and TNF-Tg (n = 4 male, n = 7 female) mice at monthly intervals from 2-5 (females) and 2-8-months (males) of age, since female TNF-Tg mice exhibit early mortality from cardiopulmonary disease at approximately 5-6-months. Further, 8-month-old WT (n = 4) and TNF-Tg males treated with anti-TNF monoclonal antibodies (n = 5) or IgG placebo isotype controls (n = 6) for 6-weeks were imaged with micro-CT every 3-weeks. For image analysis, we utilized our recently developed high-throughput and semi-automated segmentation strategy in Amira software. Synovial and osteoclast histology of ankle joints was quantified using Visiopharm. First, we demonstrated that the accuracy of automated segmentation, determined through analysis of ~9000 individual bones by a single user, was comparable in wild-type and TNF-Tg hindpaws before correction (79.2±8.9% vs 80.1±5.1%, p = 0.52). Compared to other bone compartments, the tarsal region demonstrated a sudden, specific, and significant bone volume reduction in female TNF-Tg mice, but not in males, by 5-months (4-months 4.3± 0.22 vs 5-months 3.4± 0.62 mm3, p<0.05). Specifically, the cuboid showed significantly reduced bone volumes at early timepoints compared to other tarsals (i.e., 4-months: Cuboid -24.1±7.2% vs Talus -9.0±5.9% of 2-month baseline). Additional bones localized to the anterolateral region of the ankle also exhibited dramatic erosions in the tarsal region of females, coinciding with increased synovitis and osteoclasts. In TNF-Tg male mice with severe arthritis, the talus and calcaneus exhibited the most sensitive response to anti-TNF therapy measured by effect size of bone volume change over treatment period. We demonstrated that sexually dimorphic changes in arthritic hindpaws of TNF-Tg mice are bone-specific, where the cuboid serves as a reliable early biomarker of erosive arthritis in female mice. Adoption of automated segmentation approaches in pre-clinical or clinical models has potential to translate quantitative biomarkers to monitor bone erosions in disease and evaluate therapeutic efficacy.

Carnosine, Zinc and Copper: A Menage a Trois in Bone and Cartilage Protection.

Dysregulated metal homeostasis is associated with many pathological conditions, including arthritic diseases. Osteoarthritis and rheumatoid arthritis are the two most prevalent disorders that damage the joints and lead to cartilage and bone destruction. Recent studies show that the levels of zinc (Zn) and copper (Cu) are generally altered in the serum of arthritis patients. Therefore, metal dyshomeostasis may reflect the contribution of these trace elements to the disease's pathogenesis and manifestations, suggesting their potential for prognosis and treatment. Carnosine (Car) also emerged as a biomarker in arthritis and exerts protective and osteogenic effects in arthritic joints. Notably, its zinc(II) complex, polaprezinc, has been recently proposed as a drug-repurposing candidate for bone fracture healing. On these bases, this review article aims to provide an overview of the beneficial roles of Cu and Zn in bone and cartilage health and their potential application in tissue engineering. The effects of Car and polaprezinc in promoting cartilage and bone regeneration are also discussed. We hypothesize that polaprezinc could exchange Zn for Cu, present in the culture media, due to its higher sequestering ability towards Cu. However, future studies should unveil the potential contribution of Cu in the beneficial effects of polaprezinc.

TRF-21-LNK8KEP1B as a potential novel diagnostic biomarker for enthesitis-related arthritis

ObjectivetRNA-derived fragments (tRFs) play crucial roles in the progression of various diseases, and widely distribute in human tissues, including blood and urine. The diagnosis of enthesitis-related arthritis (ERA) is based on the observation of clinical manifestations. Therefore, we aimed to investigate whether serum tRFs can be used as diagnostic markers for ERA. MethodsSerum was collected from children admitted to the Children’s Hospital Affiliated with Nanjing Medical University between February 2022 to October 2022. The expression profiles of tRFs in the serum of ERA patients (n = 5) and healthy controls (HCs; n = 5) were investigated using small RNA high-throughput sequencing. The level and diagnostic value of tRF-21-LNK8KEP1B were evaluated by real-time quantitative PCR in serum samples from 30 ERA patients and 31 HCs. The specificity and sensitivity of tRFs were determined using receiver operating characteristic analyses. Bioinformatics analysis was performed to explore and identify the potential biological pathways induced by tRFs. ResultsNinety-eight upregulated and 63 downregulated tRFs were identified in the serum. We selected tRF-21-LNK8KEP1B as a candidate marker using KEGG pathway enrichment and PCR validation. tRF-21-LNK8KEP1B was substantially increased in the serum of ERA patients compared with that in HCs. The area under the curve (AUC) for tRF-21-LNK8KEP1B in the ERA group was 0.7849. ConclusionsCollectively, we demonstrated the promising role of serum tRF-21-LNK8KEP1B -levels as a diagnostic biomarker for ERA.

The Role of Chitinase-3-Like Protein 1(YKL-40) as a Biomarker of Psoriatic Arthritis

Background Psoriatic arthritis (PsA) is a chronic multifaceted inflammatory seronegative arthritis. Plasma YKL-40 is an inflammatory biomarker. Objective To evaluate the role of Chitinase-3-like protein 1 (YKL-40) as a diagnostic biomarker in psoriatic arthritis (PsA) patients and determine its value in assessment of disease activity and severity in PsA patients. Patients and Methods This study included twenty five adult patients with clinical evidence of PsA and twenty five healthy matched age and sex as control group. All underwent history, laboratory investigation, clinical examination, assessment of disease activity using Disease Activity in PSoriatic Arthritis (DAPSA) Score and assessment of severity of PsA using Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Leeds Enthesitis Index (LEI) and examination of dactylitis. Results The mean age of patients was 39.72 ± 11.94. Also, The mean age of healthy controls was 42.88 ± 12.11. There was highly statistically significant difference regarding the serum levels of YKL- 40 (P &amp;lt; 0.01) between the patients and the control groups (P &amp;lt; 0.01). The receiver operating characteristic curve (ROC) curve of YKL -40 showed that the sensitivity and the specificity of YKL- 40 in diagnosis of PsA were 96% and 92% respectively. There were statistically significant positive correlations between YKL- 40 levels (μl/mL) and each of PASI score (p = 0.005) (r = 0.539) and DAPSA score (p = 0.007) (r = 0.526). Conclusion YKL- 40 measurement may serve as a diagnostic biomarker for PsA, as it has the potential to contribute to the fundamental processes underlying the pathogenesis of PsA. So, the results of this study suggested that the addition of YKL- 40 as a serological marker has a valuable role in diagnosis of PsA and reflection of disease activity.

Characteristics of persistent arthritis with refractory Kawasaki disease: a single-center retrospective study

Arthritis is one complication of Kawasaki disease (KD); however, the clinical features of arthritis in KD have not been well clarified. We retrospectively investigated the characteristics of persistent arthritis beyond the subacute phase of KD. In this cohort, 49 of 243 patients (20%) developed arthritis, with 33 patients (14%) experiencing persistent arthritis. Among these 33 patients, 31 (94%) had complete KD. Thirty (91%) were resistant to first intravenous immunoglobulin, and 15 (45%) required additional infliximab. Five patients (15%) developed coronary artery lesions, and 24 (73%) had oligoarthritis, mainly in large lower-extremity joints. Twenty-four patients (73%) complained of arthralgia. At arthritis onset, 16 patients (48%) presented with fever, including recurrent fever in 10 patients. Serum C-reactive protein concentration in patients with active arthritis significantly increased compared with after acute KD treatment (2.4 vs. 0.7 mg/dL, p < 0.001). Serum matrix metalloproteinase-3, a biomarker of arthritis, was significantly higher in patients with active arthritis than in remission (93.7 vs. 20.3 ng/mL, p < 0.001). Thirty (91%) and 14 (42%) patients, respectively, were treated with non-steroidal anti-inflammatory drugs and prednisolone, and they completely recovered. To summarize, persistent arthritis is a common complication in refractory KD, and adequate diagnosis and treatment are necessary.

Gene expression of S100a8/a9 predicts Staphylococcus aureus-induced septic arthritis in mice.

Septic arthritis is the most aggressive joint disease associated with high morbidity and mortality. The interplay of the host immune system with the invading pathogens impacts the pathophysiology of septic arthritis. Early antibiotic treatment is crucial for a better prognosis to save the patients from severe bone damage and later joint dysfunction. To date, there are no specific predictive biomarkers for septic arthritis. Transcriptome sequencing analysis identified S100a8/a9 genes to be highly expressed in septic arthritis compared to non-septic arthritis at the early course of infection in an Staphylococcus aureus septic arthritis mouse model. Importantly, downregulation of S100a8/a9 mRNA expression at the early course of infection was noticed in mice infected with the S. aureus Sortase A/B mutant strain totally lacking arthritogenic capacity compared with the mice infected with parental S. aureus arthritogenic strain. The mice infected intra-articularly with the S. aureus arthritogenic strain significantly increased S100a8/a9 protein expression levels in joints over time. Intriguingly, the synthetic bacterial lipopeptide Pam2CSK4 was more potent than Pam3CSK4 in inducing S100a8/a9 release upon intra-articular injection of these lipopeptides into the mouse knee joints. Such an effect was dependent on the presence of monocytes/macrophages. In conclusion, S100a8/a9 gene expression may serve as a potential biomarker to predict septic arthritis, enabling the development of more effective treatment strategies.

Modeling of photofunctional transition metals (Mn, Re, Ir) complexes towards the effective detection of uric acid (UA) as biomarker for kidney dysfunction

The potential of isatinic quinolyl Schiff bases transition metal complexes as electronic biosensors for detecting kidney dysfunction biomarker (uric acid) denoted as UA was investigated from first principles computations. The adsorption of UA onto the metal centres of Ir, Mn and Re complexes of (Z)-5-bromo-3-(quinolin-8-ylimino)indolin-2-one and (Z)-5-nitro-3-(quinolin-8-ylimino)indolin-2-one, designated as L1 and L2 were studied extensively. Uric acid has been considered an essential biomarker for oxidative stress, human arthritis, cardiomyopathy, and hyperuricemia. Biomarkers perform a pivotal role in the successful diagnosis and treatment of several diseases. Dispersion-corrected DFT calculations were performed, and the results evinced that the modelled transition metal complexes are promising candidates for UA detection. It was found that UA is chemisorbed by coordinating with the metal centers and ligands at a 3.873 Å distance on average with the adsorption enthalpies being −37.11 kcal/mol, –32.95 kcal/mol, and −21.44 for UA@L2Mn, UA@L2Re and UA@L2Ir complexes respectively. While the computed adsorption enthalpies for L1 complexes were found to be −24.47 kcal/mol. –22.11 kcal/mol and –22.19 kcal/mol respectively for UA@L1Ir, UA@L1Mn and UA@L1Re complexes showing that the L2 complexes acted as better sensors for UA. The sensitivity of UA by the metal complexes was influenced by the binding conformation of UA and the adsorption sites of the ligands. Overall, the metal complexes demonstrated high sensitivity with high values of work function up to 7.13 eV being recorded and hence making suitable substrates for work-function based sensors. Good stability and excellent conductivity even with the adsorption of UA was maintained and the desorption test-based on the transition state theory was considered and the complexes showed promising results for practical implementation as UA biosensors.

Serum metabolomic profiling identifies potential biomarkers in arthritis in older adults: an exploratory study.

Seronegative elderly-onset rheumatoid arthritis (EORA)neg and polymyalgia rheumatica (PMR) have similar clinical characteristics making them difficult to distinguish based on clinical features. We hypothesized that the study of serum metabolome could identify potential biomarkers of PMR vs. EORAneg. Arthritis in older adults (ARTIEL) is an observational prospective cohort with patients older than 60 years of age with newly diagnosed arthritis. Patients' blood samples were compared at baseline with 18 controls. A thorough clinical examination was conducted. A Bruker Avance 600MHz spectrometer was used to acquire Nuclear Magnetic Resonance (NMR) spectra of serum samples. Chenomx NMR suite 8.5 was used for metabolite identification and quantification.Student t-test, one-way ANOVA, binary linear regression and ROC curve, Pearson's correlation along with pathway analyses were conducted. Twenty-eight patients were diagnosed with EORAneg and 20 with PMR. EORAneg patients had a mean disease activity score (DAS)-Erythrocyte Sedimentation Rate (ESR) of 6.21 ± 1.00. All PMR patients reported shoulder pain, and 90% reported pelvic pain. Fifty-eight polar metabolites were identified. Of these, 3-hydroxybutyrate, acetate, glucose, glycine, lactate, and o-acetylcholine (o-ACh), were significantly different between groups. Of interest, IL-6 correlated with different metabolites in PMR and EORAneg suggesting different inflammatory activated pathways. Finally, lactate, o-ACh, taurine, and sex (female) were identified as distinguishable factors of PMR from EORAneg with a sensitivity of 90%, specificity of 92.3%, and an AUC of 0.925 (p < 0.001). These results suggest that EORAneg and PMR have different serum metabolomic profiles that might be related to their pathobiology and can be used as biomarker to discriminate between both diseases.

Cytokine Signatures in Psoriatic Arthritis Patients Indicate Different Phenotypic Traits Comparing Responders and Non-Responders of IL-17A and TNFα Inhibitors.

This study aimed to explore the dynamic interactions between 32 cytokines and biomarkers in Psoriatic Arthritis (PsA) patients to compare cytokine signatures of treatment responders and non-responders. Biomarkers were measured before and after four months of treatment in 39 PsA patients initiating either Tumor Necrosis Factor alpha inhibitor (TNFi) or Interleukin-17A inhibitor (IL-17Ai). Response to treatment was defined by the composite measure, Disease Activity in Psoriatic Arthritis (DAPSA). A two-component principal component analysis (PCA) was implemented to describe cytokine signatures comparing DAPSA50 responders and non-responders. The cytokine signature of TNFi responders was driven by the correlated cytokines interferon γ (IFNγ) and IL-6, additionally associated with IL-12/IL-23p40, TNFα, and CRP, while the cytokine signature of TNFi non-responders was driven by the correlated cytokines IL-15, IL-8, and IFNγ. IL-17Ai responders were characterized by contributions of strongly correlated Th17 inflammatory cytokines, IL-17A, IL-12/IL-23p40, IL-22 to the cytokine signature, whereas IL-17A and IL-12/IL-23p40 did not demonstrate significant contribution in IL-17Ai non-responders. Based on PCA results it was possible to differentiate DAPSA50 responders and non-responders to treatment, endorsing additional examination of cytokine interaction models in PsA patients and supporting further PsA patient immune stratification to improve individualized treatment of PsA patients.

SOXC Transcription Factors as Diagnostic Biomarkers and Therapeutic Targets for Arthritis

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common disorders that disrupt the quality of life of millions of people. These two chronic diseases cause damage to the joint cartilage and surrounding tissues of more than 220 million people worldwide. Sex-determining region Y-related (SRY) high-mobility group (HMG) box C, SOXC, is a superfamily of transcription factors that have been recently shown to be involved in various physiological and pathological processes. These include embryonic development, cell differentiation, fate determination, and autoimmune diseases, as well as carcinogenesis and tumor progression. The SOXC superfamily includes SOX4, SOX11, and SOX12, all have a similar DNA-binding domain, i.e., HMG. Herein, we summarize the current knowledge about the role of SOXC transcription factors during arthritis progression and their potential utilization as diagnostic biomarkers and therapeutic targets. The involved mechanistic processes and signaling molecules are discussed. SOX12 appears to have no role in arthritis, however SOX11 is dysregulated and promotes arthritic progression according to some studies but supports joint maintenance and protects cartilage and bone cells according to others. On the other hand, SOX4 upregulation during OA and RA was documented in almost all studies including preclinical and clinical models. Molecular details have indicated that SOX4 can autoregulate its own expression besides regulating the expression of SOX11, a characteristic associated with the transcription factors that protects their abundance and activity. From analyzing the currently available data, SOX4 seems to be a potential diagnostic biomarker and therapeutic target of arthritis.

Immunosensing for Early Detection of Rheumatoid Arthritis Biomarkers: Anti-Cyclic Citrullinated Peptide Antibodies Based on Tilted-Fiber Bragg Grating Biosensor

Rheumatoid arthritis (RA) is regarded as a chronic, immune-mediated disease that leads to the damage of various types of immune cells and signal networks, followed by inappropriate tissue repair and organ damage. RA is primarily manifested in the joints, but also manifests in the lungs and the vascular system. This study developed a method for the in vitro detection of RA through cyclic citrullinated peptide (CCP) antibodies and antigens. The diameter of a tilted-fiber Bragg grating (TFBG) biosensor was etched to 50 μm and then bonded with CCP antigens and antibodies. The small variations in the external refractive index and the optical fiber cladding were measured. The results indicated that the self-assembled layer of the TFBG biosensor was capable of detecting pre- and post-immune CCP antigen and CCP peptide concentrations within four minutes. A minimum CCP concentration of 1 ng/mL was detected with this method. This method is characterized by the sensor's specificity, ability to detect CCP reactions, user-friendliness, and lack of requirement for professional analytical skills, as the detections are carried out by simply loading and releasing the test samples onto the platform. This study provides a novel approach to medical immunosensing analysis and detection. Although the results for the detection of different concentrations of CCP antigen are not yet clear, it was possible to prove the concept that the biosensor is feasible even if the measurement is not easy and accurate at this stage. Further study and improvement are required.

Novel biomarkers of psoriatic arthritis: potential for use

Novel biomarkers of psoriatic arthritis: potential for use

The Role of Chitinase-3-Like Protein 1(YKL-40) as A Biomarker of Psoriatic Arthritis

The Role of Chitinase-3-Like Protein 1(YKL-40) as A Biomarker of Psoriatic Arthritis