Pathogenesis Of Psoriatic Arthritis Research Articles

The role of endothelial damage and dyslipidemia in the development of cardiovascular pathology in psoriatic arthritis

An increased risk of cardiovascular events has now been identified in patients with psoriatic arthritis. The chronic immune-mediated inflammation underlying psoriatic arthritis (PA) leads to the development of dyslipidemia, atherosclerosis and its complications, in particular, a high risk of cardiovascular complications. For PA, dyslipidemias are most characteristic, manifested by an increased level of low and very low density lipoproteins, triglycerides and total cholesterol, which correlates with the activity of the disease. The literature review studied the pathogenesis of dyslipidemias and vascular wall lesions in psoriatic arthritis, analyzed the literature on cardiovascular complications and mortality among patients with PA, studied the issues of total cardiovascular risk, presented the results of numerous clinical studies that allow PA to be considered a disease associated with increased the risk of cardiovascular complications. Considering the role of proinflammatory cytokines in the pathogenesis of psoriatic arthritis, early detection of endothelial lesions represents the most promising direction in the prevention of cardiovascular diseases, which are the main cause of mortality in this group of patients.

The Molecular Pathophysiology of Psoriatic Arthritis-The Complex Interplay Between Genetic Predisposition, Epigenetics Factors, and the Microbiome.

Psoriasis is a symmetric autoimmune/inflammatory disease that primarily affects the skin. In a significant proportion of cases, it is accompanied by arthritis that can affect any joint, the spine, and/or include enthesitis. Psoriasis and psoriatic arthritis are multifactor disorders characterized by aberrant immune responses in genetically susceptible individuals in the presence of additional (environmental) factors, including changes in microbiota and/or epigenetic marks. Epigenetic changes can be heritable or acquired (e.g., through changes in diet/microbiota or as a response to therapeutics) and, together with genetic factors, contribute to disease expression. In psoriasis, epigenetic alterations are mainly related to cell proliferation, cytokine signaling and microbial tolerance. Understanding the complex interplay between heritable and acquired pathomechanistic factors contributing to the development and maintenance of psoriasis is crucial for the identification and validation of diagnostic and predictive biomarkers, and the introduction of individualized effective and tolerable new treatments. This review summarizes the current understanding of immune activation, genetic, and environmental factors that contribute to the pathogenesis of psoriatic arthritis. Particular focus is on the interactions between these factors to propose a multifactorial disease model.

Insights into the pathogenesis of psoriatic arthritis from genetic studies.

Psoriatic arthritis (PsA) is a relatively common inflammatory arthritis, a spondyloarthritis (SpA), that occurs most often in patients with psoriasis, a common immune-mediated inflammatory skin disease. Both psoriasis and PsA are highly heritable. Genetic and recent genomic studies have identified variants associated with psoriasis and PsA, but variants differentiating psoriasis from PsA are few. In this review, we describe recent developments in understanding the genetic burden of PsA, linkage, association and epigenetic studies. Using pathway analysis, we provide further insights into the similarities and differences between PsA and psoriasis, as well as between PsA and other immune-mediated inflammatory diseases, particularly ankylosing spondylitis, another SpA. Environmental factors that may trigger PsA in patients with psoriasis are also reviewed. To further understand the pathogenetic differences between PsA and psoriasis as well as other SpA, larger cohort studies of well-phenotyped subjects with integrated analysis of genomic, epigenomic, transcriptomic, proteomic and metabolomic data using interomic system biology approaches are required.

Secukinumab: A Review in Psoriatic Arthritis.

Secukinumab (Cosentyx®) is a fully human monoclonal antibody that selectively targets interleukin (IL)-17A, a proinflammatory cytokine involved in the pathogenesis of psoriatic arthritis (PsA). Administered subcutaneously, the first-in-class anti-IL-17 agent is approved in numerous countries worldwide for the treatment of adults with active PsA. In the phase III FUTURE trials, secukinumab 150 or 300 mg improved the clinical signs and symptoms of PsA versus placebo in patients with active disease despite previous treatment with NSAIDs, biological disease-modifying anti-rheumatic drugs (bDMARDs) and/or tumour necrosis factor inhibitors (TNFi). The benefits of secukinumab were seen regardless of whether or not patients had received previous TNFi therapy, and were maintained during longer term (up to 5 years) treatment. In FUTURE 1 and 5, secukinumab inhibited structural joint damage and was associated with sustained low rates of radiographic progression through 1–3 years of treatment. Treatment with secukinumab improved physical function and health-related quality of life (HR-QOL) and was generally well tolerated, both in the short- and longer-term. In the head-to-head EXCEED trial, secukinumab did not quite attain statistical significance for superiority versus adalimumab in the joint domain. In conclusion, secukinumab is effective across all key PsA domains and is generally well tolerated, and thus represents a useful treatment alternative to TNFi and other bDMARDs in adult patients with active PsA.

The Role of Ultrasound in Research and Clinical Practice in Psoriatic Arthritis: Highlights From the GRAPPA Ultrasound Workshop.

Ultrasound (US) is a valuable imaging modality that can accurately identify relevant features of psoriatic arthritis (PsA), such as synovitis, tenosynovitis, and enthesitis. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Ultrasound Committee ran a workshop during the annual GRAPPA meeting that was held in July 2020. The group presented the following 3 topics: (1) the transition from psoriasis to PsA and the role of US; (2) the effect of biomechanical forces on the entheses in health and disease, and insight for PsA pathogenesis; and (3) differentiation of enthesitis from pain sensitization: use and limitations of clinical and sonographic evaluation of enthesitis. This article summarizes the key messages from this workshop.

The Effect of Methotrexate on Serum Levels of Trace/Mineral Elements in Patients with Psoriatic Arthritis

Psoriatic arthritis is a type of inflammatory arthritis that occurs in some patients with psoriasis. Clinically, low-dose methotrexate was used to treat psoriatic arthritis as a first-line agent. However, the pathogenesis of psoriatic arthritis and the mechanism of methotrexate treating psoriatic arthritis remained unclear. In recent years, a variety of side effects associated with methotrexate have been reported. In order to illuminate the role of trace/mineral elements in the pathogenesis of psoriatic arthritis and the side effect of low-dose methotrexate on blood cells and trace/mineral elements in patients with psoriatic arthritis, 37 psoriatic arthritis patients and healthy 50 people with similar age and gender were enrolled in this study. The blood cells, serum trace/mineral elements, liver function, and kidney function were determined. The results revealed that the level of serum zinc was significantly lower and copper was significantly higher in psoriatic arthritis patients in comparison with healthy control. After giving patients methotrexate intravenously (15mg weekly), their serum zinc was significantly increased, and copper was significantly decreased with symptoms relieved. Our study provided the evidence that low zinc and high copper might be associated with the pathogenesis of psoriatic arthritis, and the possible mechanism of methotrexate treating psoriatic arthritis was through elevating zinc and reducing copper in serum. Moreover, we demonstrated that low-dose methotrexate could induce liver damage to psoriatic arthritis patients.

Псориатический артрит: патогенетическое обоснование современных терапевтических подходов

Objective of the Review: To analyse and summarise information on the pathogenesis of psoriatic arthritis (PsA); to discuss therapeutic targets, actual and long-term drug therapy strategies for this disease. Key Points. PsA pathogenesis is still a matter of argument; some of its mechanisms are still studied poorly. It is assumed that, in patients with genetic predisposition, the disease is triggered by the environmental factors, dysbiosis, infections, stress, that can cause and maintain aberrant activation of the innate and adaptive immune system. We found out that increased expression of such cytokines as IL-6, TNF-α and IL-17A causes synovitis; activates neoangiogenesis, bone resorption and erosion; leads to destruction and inflammation of cartilage as a result of induction of several molecular paths in synovial fibroblasts and macrophages, endothelial cells, osteoblasts, osteoclasts, cartilage cells, and immune cells. Taking into account available information on pathogenic mechanisms of PsA and psoriasis, we have developed several drugs targeting cells, cytokines or other mediators, playing a central role in the pathogenesis of the disease. Conclusion. Currently, treatment of psoriasis and PsA involves the use of traditional basic synthetic anti-inflammatory medicines, genetically engineered biological agents, and target oral synthetic medications, particularly phosphodeisterase-4 inhibitors and Janus kinase inhibitors, a majority of which can treat the entire range of skin and bone manifestations of the disease. Taking into account the varying PsA phenotype, comorbidities and a wide range of medicinal products that can be used by medical professionals, a majority of authors are of the opinion that it is necessary to improve the algorithms of individual approaches to the management of each patient. Keywords: psoriatic arthritis; immunopathogenesis; genetically engineered biological agents.

Association between inflammasome-related polymorphisms and psoriatic arthritis

Objective: Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease associated with psoriasis. Underlying genetic factors are considered important for disease expression and prognosis of PsA. Interleukin-1β-regulating protein complexes called inflammasomes are associated with several inflammatory diseases, e.g. rheumatoid arthritis and psoriasis. The aim was to determine whether inflammasome-related genetic variation is associated with PsA susceptibility or different disease phenotypes. Method: DNA from 724 patients with PsA and 587 population-based controls from northern Sweden was analysed for single-nucleotide polymorphisms in NLRP3-Q750K (rs35829419), NLRP3 (rs10733113), CARD8-C10X (rs2043211), NLRP1 (rs8079034), and NLRP1 (rs878329). Results: Significant associations were found with the genotype AA (vs AT+TT) of rs2043211 for PsA patients compared with controls [odds ratio (OR), 95% confidence interval (CI) 1.32 (1.05–1.65), p = 0.016]; and between the C-allele of rs878329 and axial involvement of PsA [OR (95% CI) 1.37 (1.02–1.84), p = 0.035], the T-allele of rs8079034 with prescription of conventional synthetic disease-modifying anti-rheumatic drugs [OR (95% CI) 1.76 (1.23–2.53), p = 0.0020], the G-allele of rs10733113 and patients with a skin disease with early onset [OR (95% CI) 1.58 (1.13–2.21), p = 0.007], and the C-allele of rs35829419 and a destructive/deforming disease [OR (95% CI) 1.63 (1.04–2.55), p = 0.030]. Conclusions: This study is the first to show an association with a genetic polymorphism in an inflammasome-related gene, CARD8-C10X (rs2043211), in patients with PsA. Associations between different phenotypes of PsA and different polymorphisms of the inflammasome genes were also found. Our results indicate the involvement of inflammasome genes in the pathogenesis and disease expression of PsA.

Successful use of the interleukin-17A inhibitor (ixekizumab) in the treatment of psoriatic arthritis

Psoriatic arthritis (PsA) is a chronic immune-mediated disease from a group of spondyloarthritis, which is characterized by damage to the musculoskeletal system with a wide range of different clinical manifestations and is usually associated with psoriasis. Activation of the interleukin (IL) 23/IL17 axis plays a key role in the pathogenesis of PsA and psoriasis. When non-steroidal and synthetic disease-modifying antirheumatic drugs are insufficiently effective, biological drugs are recommended. In recent years, there have been considerable advances in PsA treatment with tumor necrosis factor-α (IFN-α) inhibitors and IL-12/23 inhibitors. However, in some cases, this therapy fails to provide the desired effect and a search for new treatments for PsA seems to be an urgent task. The paper desctibes a clinical case demonstrating the efficacy of the IL17A inhibitor ixekizumab in a patient with high PsA activity and recurrent uveitis in both eyes. Ixekizumab therapy resulted in positive changes as the reduced severity of articular syndrome and psoriasis and normalization of acute phase parameters. Assessing the activity of PsA over time when using ixekizumab during a year showed an average decrease in ESR from 72 to 19 mm/h, in CRP from 162.1 to 0 mg/L, BSA from 51 to 0.25%, PASI from 43. 6 to 0, DAPSA from 78.2 to 2, ASDAS-SRB from 5.11 to 1.12, BASDAI from 4.85 to 1, BASFI from 5.3 to 0.7, BASMI from 5.0 to 2.6, MASES from 6 to 0, LEI from 2 to 0, SPARCC from 6 to 0, and NAPSI from 28 to 8. Thus, this clinical case is an example of successful treatment with the IL17 inhibitor ixekizumab for PsA with recurrent uveitis in the patient who has previously received three drugs from the TNFα group without any effect.

Longitudinal profiling of the gut microbiome in patients with psoriatic arthritis and ankylosing spondylitis: a multicentre, prospective, observational study

BackgroundPsoriasis is a chronic inflammatory disease of the skin affecting 2–3% of UK population. 30% of people affected by psoriasis will develop a distinct form of arthritis within 10 years of the skin condition onset. Although the pathogenesis of psoriatic arthritis is still unknown, there is a genetic predisposition triggered by environmental factors. Limited but convincing evidence link the gut microbiome to psoriatic arthritis. The Microbiome in Psoriatic ARThritis (Mi-PART) study propose is to characterise the microbiome-metabolic interface in patients affected by psoriatic arthritis to deepen our understanding of the pathogenesis of the disease.MethodsThis is a multicentre, prospective, observational study. Psoriatic arthritis (n = 65) and ankylosing spondylitis (n = 30) patients will be recruited in addition to a control group of healthy volunteers (n = 30). Patients eligibility will be evaluated against the Criteria for Psoriatic Arthritis (CASPAR), the Bath Ankylosing Spondylitis Activity Index (BASDAI) and the healthy volunteers who fulfil study inclusion and exclusion criteria.Information regarding their medical and medication history, demographics, diet and lifestyle will be collected. All the participants in the study will be asked to complete a 7-day food diary, to provide stool samples and to complete quality of life questionnaires. Routine clinical laboratory tests will be performed on blood and urine samples. Patients and healthy volunteers with gastrointestinal symptoms, previous history of cancer, gastrointestinal surgery in the previous 6 months or alcohol abuse will be excluded from the study.DiscussionThe aim of this trial is to characterise the microbiome of psoriatic arthritis patients and to compare it with microbiome of healthy volunteers and of patient with ankylosing spondylitis in order to define if different rheumatologic conditions are associated with characteristic microbiome profiles. Investigating the role of the microbiome in the development of psoriatic arthritis could deepen our understanding of the pathogenesis of the disease and potentially open the way to new therapies.

Correlation of metabolic syndrome with serum omentin-1 and visfatin levels and disease severity in psoriasis and psoriatic arthritis.

Psoriasis and psoriatic arthritis (PsA) have been linked to metabolic syndrome (MS). The impact of adipokines on psoriasis, PsA, and MS pathogenesis has recently received investigative attention. A total of 80 subjects with psoriasis, 40 subjects with PsA, and 60 healthy controls were enrolled. Serum omentin and visfatin levels were measured, and MS presence was determined. PASI and DAS28 were used to measure disease severity for psoriasis and PsA, respectively. The prevalence of MS was determined to be 49% in psoriasis, 48% in PsA, and 28% in control groups. Rates were similar in psoriasis and PsA groups and was significantly greater when compared to control (P = .028). Diastolic blood pressure and waist circumference were significantly greater in the psoriasis group. Although the presence of MS positively correlated with age and disease duration in the psoriasis group, no significant relationships with PASI and DAS28 were found. Among all groups combined, there was no significant relationship with omentin and visfatin levels. In the psoriasis group, omentin and visfatin levels were greater in those with MS compared to those without MS. The relationships between omentin and visfatin levels with MS in patients with psoriasis and PsA has not yet been fully elucidated. These results suggest that elevated omentin and visfatin levels seen in psoriasis may be linked to MS rather than psoriasis itself. Additional research is needed to investigate the utility of these measurements as indicators of MS in patients with psoriasis.

Imaging in the diagnosis and management of peripheral psoriatic arthritis.

Psoriatic arthritis is a heterogenous disease affecting peripheral and axial joints, tendons, ligaments, and their insertions, in addition to the skin and the nails. The complexity of the involved structures has puzzled clinicians trying to understand the underlying pathology that leads to symptoms in order to choose the appropriate medications with different modes of actions. Imaging, mainly ultrasound and magnetic resonance imaging, allows of accurate detection of inflammatory changes in the musculoskeletal structures, which helps to avoid false positive and negative assessments. The linking of different anatomical structures' involvement using imaging also provides insights into the pathogenesis of psoriatic arthritis. In this review, ultrasound and magnetic resonance imaging will be discussed in depth with regard to their use in the field of peripheral psoriatic arthritis, with a focus on the literature from the last 4 years and recent advances.

Psoriatic arthritis and depressive symptoms: does systemic inflammation play a role?

Depression is commonly associated with psoriatic arthritis (PsA), but its risk factors in these patients are largely unrecognized. Pro-inflammatory cytokines involved in the pathogenesis of PsA have been associated with depression in patients without autoimmune diseases. The aim of this study was to establish whether PsA patients with and without depressive symptoms differed for general or clinical variables and serum cytokines milieu. One hundred and fifty consecutive patients with PsA were screened for depressive symptoms with Hospital Anxiety and Depression Scale (HADS-D). Patients with and without depressive symptoms were compared according to the prevalence of general risk factors for depression, comorbidities, PsA features and serum IL-6, TNF-α, and IL-17A. Fifty-eight patient (38.7%) had a depressive mood. Depressive symptoms were associated with female sex (p = 0.03) and current smoking (p = 0.05). Patients with and without depressive symptoms did not differ for general risk factors for depression and comorbidities. Depressed patients had more frequently psoriatic nail disease (p = 0.02) and significant physical disability (HAQ-DI ≥ 0.5) (p < 0.01) and were more frequently in moderate or high disease activity according to DAPSA score (p = 0.01). Depressed patients had higher serum IL-6 (p < 0.01) and comparable serum IL-17A and TNF-α. A cutoff of 2.27 pg/ml of serum IL-6 had the best ability to predict an HADS-D ≥ 8 (AUC 0.666 ± 0.044; p < 0.01). Multivariate logistic regression analysis confirmed that serum IL-6 ≥ 2.27 pg/ml was independently associated with depressive symptoms (OR 3.5; CI 1.6-7.8; p < 0.01). Higher serum Il-6 is associated with depressive symptoms. This association suggests a direct role of systemic inflammation in the modulation of mood in PsA patients. Key Points • High PsA disease activity and physical disability are associated with depression. • Higher serum levels of IL-6 are independently associated with depression in PsA. • IL-6 might play a direct role in the development of depression in PsA patients.

Current knowledge on autoantigens and autoantibodies in psoriasis.

In the past decades, clinical and experimental evidence has demonstrated that psoriasis is an immune-mediated inflammatory disease of the skin that occurs in genetically susceptible individuals. Psoriasis also shows clear autoimmune pathomechanisms, but specific cellular targets for the onset and maintenance of psoriatic lesions were not established until 2014. Since then, four psoriasis autoantigens were discovered, namely cathelicidin LL-37, melanocytic ADAMTSL5, lipid antigen PLA2G4D and keratin 17. Autoreactive T cells against these autoantigens were found in a number of patients with moderate-to-severe plaque psoriasis. Moreover, the discovery of autoantibodies against LL-37 and ADAMTSL5 and their strong association with psoriatic arthritis (PsA) suggest a potential role of these autoantibodies in the pathogenesis of PsA. This review discusses the current studies on psoriatic autoantigens and the associated circulating autoantibodies and their mechanisms involved in the development and maintenance of psoriatic plaques. Recent autoimmune evidence fuelled the discussion on psoriasis as an autoimmune skin disorder and has the potential to develop new treatment strategies with protective and therapeutic antigen-targeted methods.

Cartilage Degradation in Psoriatic Arthritis Is Associated With Increased Synovial Perfusion as Detected by Magnetic Resonance Imaging.

Objective: Even though cartilage loss is a known feature of psoriatic arthritis (PsA), research is sparse on its role in the pathogenesis of PsA and its potential use for disease detection and monitoring. Using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and dynamic contrast-enhanced MRI (DCE MRI), research has shown that early cartilage loss is strongly associated with synovial inflammation in rheumatoid arthritis (RA). The aim of this study was to determine if acute inflammation is associated with early cartilage loss in small finger joints of patients with PsA.Methods: Metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints of 17 patients with active PsA were evaluated by high-resolution 3 Tesla dGEMRIC and DCE MRI using a dedicated 16-channel hand coil. Semi-quantitative and quantitative perfusion parameters were calculated. Images were analyzed by two independent raters for dGEMRIC indices, PsA MRI scores (PsAMRIS), total cartilage thickness (TCT), and joint space width (JSW).Results: We found significant negative correlations between perfusion parameters (except Kep) and dGEMRIC indices, with the highest value at the MCP joints (KTrans: τ = −0.54, p = 0.01; Kep: τ = −0.02, p = 0.90; IAUC: τ = −0.51, p = 0.015; Initial Slope: τ = −0.54, p = 0.01; Peak: τ = −0.67, p = 0.002). Heterogeneous correlations were detected between perfusion parameters and both, total PsAMRIS and PsAMRIS synovitis sub-scores. No significant correlation was seen between any perfusion parameter and JSW and/or TCT.Conclusion: As examined by DCE MRI and dGEMRIC, there is a potential association between early cartilage loss and acute synovial inflammation in small finger joints of PsA patients.

Weighted gene co-expression network analysis identifies RHOH and TRAF1 as key candidate genes for psoriatic arthritis

Psoriatic arthritis (PsA) is inflammatory arthritis associated with psoriasis, which involves the axial joint and the distal interphalangeal joints. Its clinical features are varied, often resulting in delayed diagnosis and treatment. Improved knowledge about disease mechanisms will catalyze the rapid development of effective targeted therapies for this disease. The perturbations in the gene co-expression network may not be detected by the differential expression analysis of the microarray. This study aims to identify key modules and hub genes in psoriatic arthritis-applied WGCNA (weighted gene co-expression network analysis) on a microarray. This study downloaded the array data of GSE61281 from the gene expression overview (GEO) database, which includes 20 psoriatic arthritis samples and 12 healthy controls. The analysis was performed with the WGCNA package. Gene ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these key modules. Candidate hub genes were identified using GS and MM measures, Cytoscape, and the online database STRING. A total of 10 co-expression modules were constructed. The lightcyan module was identified as the key module. GO and KEGG pathway analyses were mainly enriched in dephosphorylation, regulation of small GTPase-mediated signal transduction, Ras signaling pathway, MAPK signaling pathway, and vascular smooth muscle contraction. Two hub genes, RHOH/TRAF1, were selected. This finding may indicate that RHOH/TRAF1 play a critical role in the pathogenesis of PsA. This is one of the first studies in PsA using WGCNA, which may provide a new research direction for further understanding of the molecular mechanism and clinical application of PsA. Key points • The WGCNA method was applied to the expression profile microarray of psoriatic arthritis and the co-expression module was constructed. • Identify the key modules by combining the onset time of psoriasis in patients with psoriatic arthritis. • Three screening methods are used to identify and verify hub genes of key modules.

Psoriatic arthritis: A systematic review of non-HLA genetic studies and important signaling pathways.

Psoriatic arthritis (PsA) is a common, chronic inflammatory disease with complex pathogenesis. In recent years, a number of susceptibility non-human leukocyte antigen (HLA) genes of PsA have been revealed, which also act as important factors in the pathogenesis of PsA as well as HLA genes. By searching the databases National Center for Biotechnology Information, Google and PubMed, 37 articles are included and 50 susceptibility non-HLA genes for PsA are presented, such as IL23A, TNIP1, TYK2, STAT4, IL12B, RUNX3 and TRAF3IP2. In these non-HLA genes, some are common genes shared with other diseases, whereas most of these susceptibility genes are related to the pathogenesis of PsA by activation or inhibition of the signaling pathways. Several signaling pathways possibly implicated in the pathogenesis of PsA are introduced in this paper, including the 2 mainly signaling pathways, IL23/Th17 signaling pathway and NF-κB signaling pathway, and the other involved signaling pathways, such as JAK-STAT signaling pathway and MAPK signaling pathway.

Sorption of Interleukins 12 and 23 Using the Developed Magnetocontrollable Ustekinumab-Based Sorbent.

The aim of the study was to assess the sorption capacity of Ustekinumab, a drug based on interleukins 12 (IL-12) and 23 (IL-23), when using it with a magnetocontrollable sorbent.Materials and Methods.To reduce the concentration of proinflammatory cytokines (IL-12, IL-23), the blood of patients with psoriatic arthritis was passed through magnetocontrollable polyacrylamide granules (MPG) of spherical shape with the particle size of 10–100 μm, obtained by emulsion polymerization. Perfusion was performed through a 10 ml column equipped with an electromagnet, into which MPG with immobilized antibodies to IL-12 and IL-23 was added. Ustekinumab, a commercial drug with concentration of monoclonal antibodies equaling 0.2 mg per 1 ml of saline was used as the source of antibodies to these interleukins. The specific sorption capacity of MPG was determined using a column filled with the granules in a volume of 0.2 ml and inducing their subsequent interaction with 1 ml of IL-12 and IL-23 solutions with increasing concentrations.The heparinized blood of 10 patients with psoriatic arthritis of various degrees of activity, who had no parenteral administration of IL-12/IL-23 inhibitors (Ustekinumab) for 12 months, was subjected to in vitro treatment. The blood of 10 healthy donors was used as the control; the perfusion procedure was similar.Results.Digital parameters were measured for each sample before and after the interaction between the sorbent and blood plasma. There was a significant decrease in cytokines from the baseline — by 99.8% (in donors) and by 99.9% (in patients). When using a carbon sorbent, their concentration decreases by 92.6% from the baseline. As a result of sorption, blood cell counts did not change reliably, which is an additional positive aspect of this procedure.Conclusion.The maximum possible decrease in the level of cytokines has great practical importance, since they play a leading role in the pathogenesis of psoriatic arthritis. The use of a synthesized Ustekinumab-based sorbent is a highly effective way of removing them simultaneously from blood plasma.

Interleukin-17A Is Produced by CD4+ but Not CD8+ T Cells in Synovial Fluid Following T Cell Receptor Activation and Regulates Different Inflammatory Mediators Compared to Tumor Necrosis Factor in a Model of Psoriatic Arthritis Synovitis.

ObjectiveInterleukin‐17A (IL‐17A) and tumor necrosis factor (TNF) contribute to the pathogenesis of psoriatic arthritis (PsA). However, their functional relationship in PsA synovitis has not been fully elucidated. Additionally, although CD8+ T cells in PsA have been recognized via flow cytometry as a source of IL‐17A production, it is not clear whether CD8+ T cells secrete IL‐17A under more physiologically relevant conditions in the context from PsA synovitis. This study was undertaken to clarify the roles of IL‐17A and TNF in the synovial fluid (SF) from patients with PsA and investigate the impact of CD8+ T cells on IL‐17A production.Methods IL‐17A+ T cells were identified by flow cytometry in SF samples from 20 patients with active PsA, blood samples from 22 treatment‐naive patients with PsA, and blood samples from 22 healthy donors. IL‐17A+ T cells were sorted from 12 PsA SF samples and stimulated using anti‐CD3/anti‐CD28 or phorbol myristate acetate (PMA) and ionomycin ex vivo, alone (n = 3) or together with autologous monocytes (n = 3) or PsA fibroblast‐like synoviocytes (FLS) (n = 5–6). To evaluate the differential allogeneic effects of neutralizing IL‐17A and TNF, SF CD4+ T cells and PsA FLS cocultures were also used (n = 5–6).ResultsFlow cytometry analyses of SF samples from patients with PsA showed IL‐17A positivity for CD4+ and CD8+ T cells (IL‐17A, median 0.71% [interquartile range 0.35–1.50%] in CD4+ cells; median 0.44% [interquartile range 0.17–1.86%] in CD8+ T cells).However, only CD4+ T cells secreted IL‐17A after anti‐CD3/anti‐CD28 activation, when cultured alone and in cocultures with PsA monocytes or PsA FLS (each P < 0.05). Remarkably, CD8+ T cells only secreted IL‐17A after 4‐ or 72‐hour stimulation with PMA/ionomycin. Anti–IL‐17A and anti‐TNF treatments both inhibited PsA synovitis ex vivo. Neutralizing IL‐17A strongly inhibited IL‐6 (P < 0.05) and IL‐1β (P < 0.01), while anti‐TNF treatment was more potent in reducing matrix metalloproteinase 3 (MMP‐3) (P < 0.05) and MMP‐13.Conclusion CD8+ T cells, in contrast to CD4+ T cells, in SF specimens obtained from PsA patients did not secrete IL‐17A following T cell receptor activation. Overlapping, but distinct, effects at the level of inflammatory cytokines and MMPs were found after neutralizing IL‐17A or TNF ex vivo in a human model of PsA synovitis.

Proteoglycan loss in the articular cartilage is associated with severity of joint inflammation in psoriatic arthritis\u2014a compositional magnetic resonance imaging study

BackgroundEven though cartilage loss is a known feature of psoriatic arthritis (PsA), little is known about its role in the pathogenesis of PsA. Using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) as a non-invasive marker of the tissue’s proteoglycan content, such early (i.e., pre-morphological) changes have been associated with inflammation in rheumatoid arthritis (RA). Yet, this association has not been studied before in PsA.MethodsThe metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints of 17 patients with active PsA were evaluated by high-resolution clinical standard morphological and dGEMRIC sequences using a 3T MRI scanner (Magnetom Skyra, Siemens) and a dedicated 16-channel hand coil. Images were analyzed by two independent raters for dGEMRIC indices, PsA MRI scores (PsAMRIS), and total cartilage thickness (TCT). Kendall tau correlation coefficients (τ) were calculated.ResultsWe found significant negative correlations between dGEMRIC indices and total PsAMRIS (τ = − 0.5, p = 0.012), synovitis (τ = − 0.56, p = 0.006), flexor tenosynovitis (τ = − 0.4, p = 0.049), and periarticular inflammation (τ = − 0.72, p < 0.001). Significant positive correlations were found between TCT and dGEMRIC indices at all joint levels (τ = 0.43, p < 0.001). No significant correlations were determined between dGEMRIC indices and bone erosion, bone edema, or bone proliferation.ConclusionIn PsA, proteoglycan loss as assessed by dGEMRIC is associated with periarticular inflammation, synovitis, and flexor tenosynovitis, but not with bone erosion or proliferation. Thereby, these findings contribute to in vivo concepts of the disease’s pathophysiology. Beyond morphology, advanced MRI techniques may be used to assess cartilage composition in PsA and to identify early changes in the cartilage as an imaging biomarker with potential application in detection, monitoring, and prediction of outcomes of PsA.Trial registration2014123117, December 2014.