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Psoriatic Arthritis

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Psoriatic Arthritis. Core disease mechanisms, molecular and cellular pathw...

2026-05-08
Asta MONDO:0011849 Model: Asta Scientific Corpus Retrieval 19 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Psoriatic Arthritis. Core disease mechanisms, molecular and cellular pathw...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 19
  • Snippets retrieved: 20

Relevant Papers

[1] Histopathology of Psoriatic Arthritis Synovium—A Narrative Review

  • Authors: C. Tenazinha, R. Barros, J. Fonseca, E. Vieira-Sousa
  • Year: 2022
  • Venue: Frontiers in Medicine
  • URL: https://www.semanticscholar.org/paper/253730e68e314db4b2d4cf81a495baedebf43669
  • DOI: 10.3389/fmed.2022.860813
  • PMID: 35847785
  • PMCID: 9283901
  • Citations: 16
  • Influential citations: 1
  • Summary: The psoriatic synovium shares general features of chronic inflammation with rheumatoid arthritis and other arthritis, such as hyperplasia of the intimal lining layer, sublining influx of inflammatory cells and neoangiogenesis, but recognizing disease-specific histopathologic findings may help in diagnosis and definition of therapeutic targets.
  • Evidence snippets:
  • Snippet 1 (score: 0.532) > Psoriatic arthritis (PsA) is a chronic inflammatory disease with high clinical heterogeneity that occurs the most commonly in patients with previously diagnosed psoriasis (Pso). It can involve joints, with heterogeneous patterns, and periarticular structures, such as the enthesis, tendon sheets, paratenons, but also the bone and the subcutaneous fat (1). Inflammation is considered to develop adjacent to bone insertions, affecting the enthesis and the synovium, and being associated with both processes of bone destruction and new bone formation. Clinical heterogeneity results from a wide range of severity and clinical features, that vary according to the tissues and body sites involved (2,3). Psoriatic arthritis pathogenesis is complex and detailed disease mechanisms are still unclear, with underlying polygenic and environmental predisposing factors. It is associated to type I major histocompatibility complex (MHC) alleles, with risk polymorphisms in genes related to interleukins (IL) 23 and 12, nuclear factor κB and tumor necrosis factor (TNF) that, when dysregulated, can promote the activation of inflammatory pathways (1). The study of psoriatic joint disease at the histopathology level has helped to understand disease mechanisms and may unravel new therapeutic targets and biomarkers, improving early diagnosis and treatment. > Available literature consists of either study reports or reviews of specific aspects, that often lack comparison to the most important synovitis counterpart of PsA, which is rheumatoid arthritis (RA). Herein we provide a descriptive and detailed description of the histopathologic findings concerning all levels of the synovial layer, aiming to identify what is known and what is yet to be understood, supporting physicians in biopsy interpretation and investigators in establishing questions.

[2] Molecular treatment trajectories within psoriatic T lymphocytes: a mini review

  • Authors: Martyna Kuczyńska, M. Gabig-Cimińska, M. Moskot
  • Year: 2023
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/e570bf86f327d17fe6f9b0c583ef3591f706928e
  • DOI: 10.3389/fimmu.2023.1170273
  • PMID: 37251381
  • PMCID: 10213638
  • Citations: 2
  • Summary: Despite recent drug development having mainly centred on biological therapies for Ps, yet displaying serious limitations, SMDs acting on specific pathway factor isoforms or single effectors within T cell, could represent a valid innovation in real-world treatment patterns in patients with Ps.
  • Evidence snippets:
  • Snippet 1 (score: 0.499) > In Ps, both skin-associated cells and those recruited from the circulatory system, belonging to the acquired and innate immune systems, especially T lymphocytes (T cells), are involved in complex feedback mechanisms of the disease pathophysiology (8-13). The discovery that topical treatments for skin symptoms alter the T cells' phenotype has drawn a special attention to the molecular pathways modulated in immune cells under Ps (14). Except for the intracellular cross-talk, however, the interplay between the molecules involved in different signalling tracks (i.e. throughout calcium (Ca 2+ )/calcineurin (CaN)/nuclear factor of activated T-cell (NFAT), mitogen-activated protein kinase (MAPK)/c-Jun Nterminal kinase (JNK), phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways) in T cells is of concern in the last few years, identifying them as potential targets in the management of Ps (7). At the same time, it became obvious that larger and further studies are desirable to fully explore signalling cascades involved in the pathogenesis of the disease, especially to accomplish knowledge gaps regarding pathological mechanisms within psoriatic T lymphocytes. The creation of Ps disease atlas showing a road map of intracellular molecular pathways and their regulation network supported by a library of therapeutic entities would be a highly respected and lucrative approach in the medical community as per our vision. A rather wide point of view must be mapped by connecting each piece of information, which consequently can help disease navigate and curing. Furthermore, the "new use of old medicine" would also refer to the development of new indications or new uses of drugs that were previously marketed for other purposes. Such innovative approach to research fits perfectly into the "me-too" strategy era (15), allowing to find the most appropriate molecule dedicated to the most effective disease regulation mode.
  • Snippet 2 (score: 0.446) > Autoimmune diseases are reaching epidemic levels, in part, because there are so many of them. Current medicine lists between 80 and 100 different types of autoimmune disorders or diseases. Some of the more common ones include Psoriatic (Ps) disease, a non-communicable skin and/or joint condition, currently regarded as an immune-mediated inflammatory disease (IMID) (1)(2)(3)(4). Various molecular and cellular pathways are implicated in Ps development and progression, as well as in the pathogenic mechanisms associated with an inflammation in this hyperimmune condition. Our understanding of this complex network and its tight regulation, however, turns out to be still in its infancy. Such a situation, while frustrating, offers an opportunity for further progress in the development of therapies thanks to the potential increase in our knowledge that is taking place now. It actually allows us to refine the current treatment options as well as define novel ones, focused not only on stopping attacks in progress and managing symptoms of Ps, but also on targeting the roots of disease processes. This is trying to be accomplished by using therapeutic compounds, such as Small Molecule Drugs (SMDs), developed for innovative strategies targeting any portion of a molecule, regardless of the target's cellular location, in order to depress the immune system and reduce inflammation, alleviating other symptoms at the same time (5)(6)(7). Recent advances in understanding the pathogenesis of the Ps have already led to the development of a number of SMDs that have a low molecular weight, making them penetrate cells easily and affecting molecular pathways by targeting important cellular entities. They have advantages like oral routes of administration, decreasing healthcare costs and fewer immunological adverse events compared to biologics (6). Besides, we would like to point out the fact that SMDs can be developed not only from leads derived from rational drug design, but also isolated from natural resources, leading to the innovation of more desirable treatments with minimum side effects possible. > In Ps, both skin-associated cells and those recruited from the circulatory system, belonging to the acquired and innate immune systems, especially T lymphocytes (T cells), are involved in complex feedback mechanisms of the disease pathophysiology (8-13).

[3] Metabolic changes in psoriatic skin under topical corticosteroid treatment

  • Authors: B. Sitter, M. Johnsson, J. Halgunset, T. Bathen
  • Year: 2013
  • Venue: BMC Dermatology
  • URL: https://www.semanticscholar.org/paper/2fd048568eb68b2abc3d6bcca488188bb153d686
  • DOI: 10.1186/1471-5945-13-8
  • PMID: 23945194
  • PMCID: 3751591
  • Citations: 42
  • Influential citations: 1
  • Summary: It is demonstrated that metabolism in psoriatic skin becomes similar to that of un involved skin after effective corticosteroid treatment, and tissue levels are becoming more similar to metabolite levels in uninvolved skin.
  • Evidence snippets:
  • Snippet 1 (score: 0.484) > Psoriasis is a common immune-mediated disease that affects the skin and joints. The cause of the disease remains unknown. Many patients have a genetic predisposition. The disease affects around 2-3% of the population worldwide. Clinically, psoriatic plaques are characterized by sharply demarcated erythematous lesions with thick silvery scales, often distributed in a symmetrical pattern. Histopathologically there is hyperproliferation of epidermal cells and an inflammatory cell infiltrate [1]. There is increasing awareness that psoriasis is a multisystem affection with substantial comorbidity, particularly of cardiovascular diseases and metabolic syndrome [2]. The course is that of a chronic, relapsing disease which requires long term treatment. Various topical and systemic treatment options exist for psoriatic lesions. Topical corticosteroids remain the cornerstone, either used as monotherapy or in combination with other treatment modalities. These agents exert anti-inflammatory and immunosuppressive effects by stimulation or inhibition of the genes involved in inflammatory pathways, including inhibition of cytokine production and reduction of such mediators of inflammation as prostaglandins and leucotrienes, inhibition of T-cell proliferation and T-cell dependent immunity, and suppression of fibroblast and endothelial cell functions [3,4]. Corticosteroids also have anti-proliferative effects, by delaying the onset of DNA synthesis and decreasing the mitotic rate [5]. > Molecular studies of outbreak and healing of psoriatic lesions can provide insight in the underlying biological processes. Genome wide association scans (GWAS) have identified genetic susceptibility factors [6], and molecular analysis have revealed associations of psoriasis with specific molecular pathways [7,8]. Detailed molecular characterization of autoimmune diseases can provide information about mechanisms involved in disease progression and action of drugs, and also provide biomarkers to predict and monitor disease course. Cellular enzymatic processes involve small molecular metabolites as substrates, intermediates and end products, and such metabolites are crucial in energy turnover and membrane synthesis.

[4] Integration of Immunome With Disease-Gene Network Reveals Common Cellular Mechanisms Between IMIDs and Drug Repurposing Strategies

  • Authors: Abhinandan Devaprasad, T. Radstake, A. Pandit
  • Year: 2019
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/da3d168a672593e5da82bb4178e49118bc4b3170
  • DOI: 10.3389/fimmu.2021.669400
  • PMID: 34108969
  • PMCID: 8181425
  • Citations: 13
  • Summary: The method identified top DACs, DAGs, common pathways, and proposed potential drug repurposing targets between IMIDs and built the DIME tool, paving way for future (pre-)clinical research.
  • Evidence snippets:
  • Snippet 1 (score: 0.482) > Objective Development and progression of immune-mediated inflammatory diseases (IMIDs) involve intricate dysregulation of the disease associated genes (DAGs) and their expressing immune cells. Due to the complex molecular mechanism, identifying the top disease associated cells (DACs) in IMIDs has been challenging. Here, we aim to identify the top DACs and DAGs to help understand the cellular mechanism involved in IMIDs and further explore therapeutic strategies. Method Using transcriptome profiles of 40 different immune cells, unsupervised machine learning, and disease-gene networks, we constructed the Disease-gene IMmune cell Expression (DIME) network, and identified top DACs and DAGs of 12 phenotypically different IMIDs. We compared the DIME networks of IMIDs to identify common pathways between them. We used the common pathways and publicly available drug-gene network to identify promising drug repurposing targets. Result We found CD4+Treg, CD4+Th1, and NK cells as top DACs in the inflammatory arthritis such as ankylosing spondylitis (AS), psoriatic arthritis, and rheumatoid arthritis (RA); neutrophils, granulocytes and BDCA1+CD14+ cells in systemic lupus erythematosus and systemic scleroderma; ILC2, CD4+Th1, CD4+Treg, and NK cells in the inflammatory bowel diseases (IBDs). We identified lymphoid cells (CD4+Th1, CD4+Treg, and NK) and their associated pathways to be important in HLA-B27 type diseases (psoriasis, AS, and IBDs) and in primary-joint-inflammation-based inflammatory arthritis (AS and RA). Based on the common cellular mechanisms, we identified lifitegrast as potential drug repurposing candidate for Crohn’s disease, and other IMIDs. Conclusion Our method identified top DACs, DAGs, common pathways, and proposed potential drug repurposing targets between IMIDs. To extend our method to other diseases, we built the DIME tool. Thus paving way for future (pre-)clinical research.

[5] The cardiometabolic conditions of psoriatic disease

  • Authors: E. Toussirot, I. Gallais-Serezal, F. Aubin
  • Year: 2022
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/3223edff0217b4cde6195064f6999082db825e2d
  • DOI: 10.3389/fimmu.2022.970371
  • PMID: 36159785
  • PMCID: 9492868
  • Citations: 29
  • Summary: The available evidence on the epidemiology, clinical aspects and mechanisms of cardiometabolic conditions in patients with psoriasis and psoriatic arthritis are summarized.
  • Evidence snippets:
  • Snippet 1 (score: 0.477) > Psoriasis (PsO) and psoriatic arthritis (PsA), together known as psoriatic disease (PsD), are immune-mediated diseases with a chronic and relapsing course that affect the skin, the joints or both. The pathophysiology of PsO is complex and involves abnormal expression of keratinocytes and infiltration of the skin with dendritic cells, macrophages, neutrophils and T lymphocytes. Around 30% of patients with PsO develop arthritis with axial and/or peripheral manifestations. Both PsO and PsA share similar Th1- and Th17-driven inflammation, with increased production of inflammatory cytokines, including TNFα, IFN-γ, IL-17, IL-22, IL-23 in the skin and the synovial membrane. PsD is associated with a high burden of cardiometabolic diseases such as hypertension, diabetes, dyslipidemia, obesity, metabolic syndrome and cardiovascular (CV) complications as compared to the general population. These comorbidities share common immunopathogenic pathways linked to systemic inflammation, and are associated with the extent and severity of the disease. Morever, they can influence treatment outcomes in PsD. In this short review, we summarize the available evidence on the epidemiology, clinical aspects and mechanisms of cardiometabolic conditions in patients with PsD. We also discuss the impact of targeted treatments such as methotrexate and biological agents on these cardiometabolic conditions.

[6] Biological drugs targeting the immune response in the therapy of psoriasis

  • Authors: S. Pastore, E. Gubinelli, L. Leoni, D. Raskovic, L. Korkina
  • Year: 2008
  • Venue: Biologics : Targets & Therapy
  • URL: https://www.semanticscholar.org/paper/bdb05c19fa9b6a61c44172ac081f5af73d5e8ec5
  • DOI: 10.2147/BTT.S2763
  • PMID: 19707449
  • PMCID: 2727880
  • Citations: 20
  • Summary: Recent findings on the molecular pathways relevant to the inflammatory response in psoriasis are overviewed and clinical experience with the drugs currently employed in the dermatologic manifestations, namely etanercept, infliximab, and efalizumab are presented.
  • Evidence snippets:
  • Snippet 1 (score: 0.464) > Chronic plaque psoriasis affects more than 2% of world population, has a chronic recurrent behavior, gives a heavy burden to the patients’ quality of life, and hence remains a huge medical and social problem. The clinical results of conventional therapies of psoriasis are not satisfactory. According to the current knowledge of the molecular and cellular basis of psoriasis, it is defined as an immune-mediated chronic inflammatory and hyperproliferative skin disease. A new generation of biological drugs, targeting molecules and cells involved into perturbed pro-inflammatory immune response in the psoriatic skin and joints, has been recently designed and applied clinically. These biological agents are bioengineered proteins such as chimeric and humanized antibodies and fusion proteins. In particular, they comprise the antitumor necrosis factor-α agents etanercept, infliximab, and adalimumab, with clinical efficacy in both moderate-severe psoriasis and psoriatic arthritis, and the anti-CD11a efalizumab with selective therapeutic action exclusively in the skin. Here, we overview recent findings on the molecular pathways relevant to the inflammatory response in psoriasis and present our clinical experience with the drugs currently employed in the dermatologic manifestations, namely etanercept, infliximab, and efalizumab. The growing body of clinical data on the efficacy and safety of antipsoriasis biological drugs is reviewed as well. Particular focus is given to long-term safety concerns and feasibility of combined therapeutic protocols to ameliorate clinical results.

[7] An Actual Insight into the Pathogenic Pathways of Ankylosing Spondylitis

  • Authors: Emilia Păsăran, A. Diaconu, Corina Oancea, A. Bălănescu, S. Aurelian et al.
  • Year: 2024
  • Venue: Current Issues in Molecular Biology
  • URL: https://www.semanticscholar.org/paper/a8625e59eee3e066a092d24e66e7a6e7a4ac6b9a
  • DOI: 10.3390/cimb46110762
  • PMID: 39590356
  • PMCID: 11592934
  • Citations: 8
  • Summary: The current article aims to update and systematize the knowledge accumulated so far on this topic, focusing on the mechanisms that have been involved in the onset, progression, and severity of ankylosing spondylitis.
  • Evidence snippets:
  • Snippet 1 (score: 0.460) > Spondyloarthritis refers to a broad group of conditions that include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis associated with Crohn’s disease or ulcerative colitis. They have been classified by the ASAS group (ASsessment in Ankylosing Spondylitis) into axial spondyloarthritis and peripheral spondyloarthritis. Common features include the absence of autoantibodies, genetic predisposition, and clinical aspects such as axial joint involvement, peripheral manifestations, and extra-articular involvement. However, the pathogenic mechanisms remain complex and incompletely elucidated, despite the fact that the specialized literature has described several pathways that act in synergy: genetic predisposition, environmental factors (infections and mechanical stress), or innate and acquired immune mechanisms. Finally, an inflammatory response is triggered by the recruitment of a large number of inflammatory cells and the release of innate cytokines in the affected areas: joints or periarticular or extraarticular tissues. The current article aims to update and systematize the knowledge accumulated so far on this topic, focusing on the mechanisms that have been involved in the onset, progression, and severity of ankylosing spondylitis.

[8] The Use of Biologic and Targeted Synthetic Disease-Modifying Drugs in the Treatment of Psoriatic Arthritis

  • Authors: Rafal Ali, Arthur N. Lau, Lawrence H. Brent
  • Year: 2024
  • Venue: Biologics
  • URL: https://www.semanticscholar.org/paper/9315c48bd3d2d7183484705e30ad6338a3a02d2b
  • DOI: 10.3390/biologics5010001
  • Summary: Various treatment options, focusing on biologic and targeted synthetic disease-modifying antirheumatic drugs, are discussed, targeting different inflammatory pathways in psoriatic arthritis.
  • Evidence snippets:
  • Snippet 1 (score: 0.456) > Psoriatic arthritis is a complex, systemic inflammatory condition that has similarities with both psoriasis and other inflammatory joint diseases, such as rheumatoid arthritis and spondyloarthritis. Although the precise mechanisms of PsA are not known, it is thought to result from a combination of genetic predisposition and environmental triggers that lead to inflammatory processes within both the skin and joints [25][26][27] (Figure 7). Despite these shared pathways, the specific immune mechanisms and clinical manifestations can vary significantly between the skin and joint disease. > IL-23 signaling pathways (IL-23R), which play significant roles in the inflammatory process characteristic of PsA and PsO [31]. > Environmental factors also play a role in the development of PsA, especially in individuals with psoriasis. Potential triggers include infections like streptococcal infection, as well as trauma and obesity. [32,33]. Furthermore, changes in the gut and skin microbiomes might contribute to disease pathogenesis [34,35], although it is not clear whether these changes are causal or correlative. Dysbiosis in the gut may trigger IL-23 production [36]. IL-23 is produced by resident CD14+ myeloid cells in the enthesis [37], which activates resident CD4-, CD8-, and IL-23R+ T cells [38]. The relationship between environmental factors and genetic predisposition underscores the multifactorial nature of PsA. > The immune responses in PsA are driven by a dysregulation of both innate and adaptive immunity [39]. Key players include T cells, particularly CD8+ T cells, and monocytes, which contribute to inflammation in the skin and joints [40,41]. Cytokine pathways, especially those involving TNF-α, IL-23/IL-17, and IL-22 [36,42], play crucial roles in the pathogenesis of PsA, as these cytokines are found at elevated levels in affected tissues. The overlap of immune pathways in PsA and psoriasis supports the idea of shared pathogenetic origins, although the distinct clinical manifestations in skin and joint disease indicate unique underlying mechanisms in each [36,43,44].

[9] Proprotein Convertase Subtilisin/Kexin Type 9, Angiopoietin-Like Protein 8, Sortilin, and Cholesteryl Ester Transfer Protein—Friends of Foes for Psoriatic Patients at the Risk of Developing Cardiometabolic Syndrome?

  • Authors: J. Krahel, A. Baran, T. Kamiński, I. Flisiak
  • Year: 2020
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/29ef0ba870ea75d9f92d8c3bcfd919ccf3548724
  • DOI: 10.3390/ijms21103682
  • PMID: 32456228
  • PMCID: 7279158
  • Citations: 18
  • Influential citations: 1
  • Summary: The role of four proteins: proprotein convertase subtilisin/kexin type-9 (PSCK9), angiopoietin-like protein 8 (ANGPLT8), sortilin (SORT1), and cholesteryl ester transfer proteins (CEPT) as plausible links between psoriasis and CMS are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.454) > Psoriasis is a common, disfiguring, and stigmatizing immune-metabolic skin disease affecting approximately 2-4% of the world population [1,2]. In history, psoriasis was considered as a solely dermatological condition altering the skin, nails, and joints with unexplained pathophysiology. Since 2000, there has been a rapid rise in the pairing of psoriasis with the immune system and metabolic syndrome, which has led scientists to identify psoriasis as an immune-metabolic disease. Psoriatic patients tend to develop metabolic syndrome (MetS), including abdominal obesity, cardiometabolic diseases (CMDs), diabetes mellitus (DM), dyslipidemia, and non-alcoholic fatty liver disease (NALFD) [3]. Today, many factors lead to the occurrence and progression of the disease, namely, genetic predisposition, lifestyle, viral and bacterial infections, and numerous medications used in cardiology and immunology [1,4]. The exact etiology and molecular background of psoriasis have not been dealt with in-depth, but recent years have produced abundant new clinical findings that clarified part of psoriasis pathophysiology. > First, the innate and adaptive immune responses and cytokines-dependent mechanisms are considered fundamental pathological processes priming the occurrence and severity of the disease. Inflammation is the immune system's response to harmful stimuli, such as pathogens, damaged cells, toxic compounds, or irradiation. In general, a lasting, pro-inflammatory state is found in various conditions, including atherosclerosis, obesity, and psoriasis [1]. Acute and chronic phases of inflammatory process have been linked to increased morbidity of cardiovascular disease, neurological disorders, different types of cancer, and higher risk of deaths from these conditions. Interestingly, studying the plethora of different molecular and genomic pathways related to inflammatory processes resulted in the identification of pathways that are common for both, psoriasis and CMS.

[10] Ex vivo cytokine production in psoriatic disease: Towards specific signatures in cutaneous psoriasis and peripheral psoriatic arthritis

  • Authors: G. Larid, A. Delwail, Thomas Dalle, Philippe Vasseur, C. Silvain et al.
  • Year: 2022
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/b655abb93d1539aec706f058d00d2ecc23d4d69a
  • DOI: 10.3389/fimmu.2022.993363
  • PMID: 36426370
  • PMCID: 9678922
  • Citations: 7
  • Summary: PsO and the different PsA subtypes exhibit distinct ex vivo cytokine production profiles and common features of the so-called PsD, and the crucial role of immune cell interactions with different patterns of interaction depending on clinical phenotype is highlighted.
  • Evidence snippets:
  • Snippet 1 (score: 0.451) > Psoriasis is an inflammatory cutaneous disorder with prevalence up to 3% of people in industrialized countries (1). Originally described as a skin and/or articular pathology, psoriasis appears as a disease involving other tissue damage. In the last ten years, the concept of "psoriatic disease" (PsD) has emerged, which encompasses all the clinical aspects of so-called cutaneous psoriasis (PsO), psoriatic arthritis (PsA), and associated comorbidities such as cardio-metabolic disorders (2)(3)(4)(5). As PsD is a systemic disease, patients can present features of PsO, PsA, or both. Numerous studies focusing on PsO patients do not indicate if patients have articular involvement or not. Likewise, among PsO patients, many patients suffering from PsA are undiagnosed (6). This common vagueness in population's description creates a potential bias both for the clinical diagnosis which determines the follow-up and treatment of patients, and for studies describing the physiopathological mechanisms of PsD, in which the two clinical entities may not be clearly differentiated from one to another. > PsD is a polygenic inflammatory disorder of which the pathophysiology raises numerous questions (7,8). Interestingly, among the multiple polymorphisms associated with PsO or PsA, a significant number involves genes encoding for cytokines such as IL-12B, IL-23A, IL-23R, IL-13, IL-36G, IL-20, TNFAIP3 or TNFIP1 (7)(8)(9), leading to investigations of cytokine profiles in PsO or PsA in order to determine specific cytokine signatures. To date, different biological approaches have been applied to PsD, including serum analysis, transcriptomic analysis, and ex vivo studies, but the majority of these studies do not discriminate between the two clinical entities. While transcriptomic approaches from inflamed skin or synovial tissue samples provide relevant information on the pathophysiology of both diseases, their use in routine practice is not possible for diagnosis, insofar it requires invasive techniques to obtain samples.

[11] Psoriasis, psoriatic arthritis, and rheumatoid arthritis: Is all inflammation the same?

  • Authors: L. Coates, O. FitzGerald, P. Helliwell, C. Paul
  • Year: 2016
  • Venue: Seminars in arthritis and rheumatism
  • URL: https://www.semanticscholar.org/paper/3cc18d8ab18be64eb75c28ea6be79c285f017bec
  • DOI: 10.1016/j.semarthrit.2016.05.012
  • PMID: 27388027
  • Citations: 154
  • Influential citations: 4
  • Summary: Increased understanding of the immunopathogenesis allowed development of targeted treatments; however, despite a variety of potentially predictive genetic, protein and cellular biomarkers, there is still significant unmet need in these three inflammatory disorders.
  • Evidence snippets:
  • Snippet 1 (score: 0.448) > OBJECTIVES > To review the pathophysiology, co-morbidities, and therapeutic options for psoriasis, psoriatic arthritis and rheumatoid arthritis in order to further understand the similarities and differences in treatment paradigms in the management of each disease. New targets for individualized therapeutic decisions are also identified with the aim of improving therapeutic outcome and reducing toxicity. > SEARCH STRATEGY > Using the PubMed database, we searched literature published from 2000 to 2015 using combinations of the key words "psoriasis," "psoriatic arthritis," "rheumatoid arthritis," "pathogenesis," "immunomodulation," and "treatment." > INCLUSION AND EXCLUSION CRITERIA > This was a non-systematic review and there were no formal inclusion and exclusion criteria. > DATA EXTRACTION > Abstracts identified in the search were screened for relevance and articles considered appropriate evaluated further. References within these selected articles were also screened. Information was extracted from 198 articles for inclusion in this report. > DATA SYNTHESIS > There was no formal data synthesis. Articles were reviewed and summarized according to disease area (psoriasis, psoriatic arthritis, and rheumatoid arthritis). > HEADLINE RESULTS > The pathophysiology of psoriasis, psoriatic arthritis, and rheumatoid arthritis involves chronic inflammation mediated by pro-inflammatory cytokines. Dysfunction in integrated signaling pathways affecting different constituents of the immune system result in varying clinical features in the three diseases. Co-morbidities, including cardiovascular disease, malignancies, and non-alcoholic fatty liver disease are increased. Increased understanding of the immunopathogenesis allowed development of targeted treatments; however, despite a variety of potentially predictive genetic, protein and cellular biomarkers, there is still significant unmet need in these three inflammatory disorders.

[12] State of the Art Review on the Treatment of Psoriatic Disease

  • Authors: E. Pelechas, E. Kaltsonoudis, Michalis P. Migkos, N. Koletsos, P. Karagianni et al.
  • Year: 2024
  • Venue: Mediterranean Journal of Rheumatology
  • URL: https://www.semanticscholar.org/paper/0dc58150e9ccdb1ff88f0971378f3cc7ca6e45df
  • DOI: 10.31138/mjr.040123.sot
  • PMID: 38736956
  • PMCID: 11082764
  • Citations: 2
  • Summary: This review aims to highlight the newest treatments for psoriatic disease, which are expected to significantly reduce unmet needs and treatment gaps.
  • Evidence snippets:
  • Snippet 1 (score: 0.448) > Psoriasis is a chronic inflammatory disease that is characterised by skin lesions which in some cases are accompanied by systemic manifestations.Due to its high heterogeneity, the World Health Organisation (WHO) has classified psoriasis as a serious disease. 1 It affects 2-3% of the population and presents significant effects on the physical and mental health of the patients. 2,3Psoriatic lesions result from an increased proliferation and disturbed differentiation of the keratinocytes. 4In the majority of cases, skin lesions precede joint manifestations as well as other organ infestations (bowel, eyes).Given the aforementioned various clinical manifestations, the term psoriatic disease probably reflects in a better manner the whole clinical picture of those affected. 5In addition, psoriatic disease may develop a variety of well-known associated comorbidities including cardiovascular disease, obesity and metabolic syndrome, diabetes, osteoporosis, malignancy, fatty liver disease, depression, and anxiety. 6arious immune-mediated cellular pathways such as that of TNF-α, IL-23, and IL-17 are involved in the pathophysiology of psoriasis and psoriatic arthritis, and their understanding has led to remarkably better control of it. 4,7owadays, there are various treatment options that are already approved by the regulatory bodies and rely on blocking those cytokines with good to excellent results so far.The main aim of the so-called targeted treatments with biologics is the long-term modulation of the psoriatic disease, with immediate but also long-term results of the signs and symptoms of the disease including the radiological progression.Finally, there is a growing body of evidence that not only the psoriatic disease in sine gets

[13] Molecular profiling of clinical remission in psoriatic arthritis reveals dysregulation of FOS and CCDC50 genes: a gene expression study

  • Authors: M. M. Angioni, A. Floris, Ignazio Cangemi, M. Congia, E. Chessa et al.
  • Year: 2023
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/543e695473c5930c2897fc60a5e3751548479d61
  • DOI: 10.3389/fimmu.2023.1274539
  • PMID: 37965313
  • PMCID: 10641465
  • Citations: 4
  • Influential citations: 1
  • Summary: The transcriptomic profile of clinical remission in PsA is similar to a healthy condition, but not identical, differing for the expression of FOS and CCDC50 genes, which appears to play a key role in its achievement.
  • Evidence snippets:
  • Snippet 1 (score: 0.446) > Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by wide clinical heterogeneity due to the variable combination of six major domains, namely, skin and nail psoriatic lesions, peripheral arthritis, axial disease, dactylitis, and enthesitis (1). It is recognized as a potentially disabling disease, as late and inadequate control of disease activity may result in structural damage and disability (2). > According to the European Alliance of Associations for Rheumatology (EULAR) and the Group for Research in Psoriasis and PsA (GRAPPA) recommendations, treatment of PsA should aim primarily at reaching the target of remission by regular disease activity assessment and appropriate adjustment of therapy (3,4). Although this approach represents one of the strongest and most widely shared recommendations, there are still relevant issues regarding its application in clinical practice. In particular, the definition of remission is still open to discussion among experts and represents a significant challenge in the management of PsA (5). Several definitions of clinical remission, based on composite indices combining objective (e.g., tender and swollen joint count or enthesitis and dactylitis count (6)) and subjective (e.g., scales for pain or general health) measurements of disease activity are currently used in clinical practice and trials (7). However, the clinical heterogeneity of PsA, the potential persistence of subclinical disease activity demonstrated in ultrasonography studies, and the possible progression of structural damage in patients classified as in clinical remission (8), highlight the urgent need for a sensitive and specific biomarker supporting the accurate identification of remission. > Several genetic, circulating, and tissue factors have been studied as biomarkers in the management of different aspects of PsA, including diagnosis and assessment or prediction of disease activity, severity, and response to treatment (9)(10)(11)(12)(13). However, none of these has been extensively validated and then translated into routine clinical practice (10,14). In particular, despite remission being recommended as the primary goal in PsA treatment, to our knowledge, no studies have been specifically designed to identify the underlying molecular mechanisms and potential biomarkers.

[14] Psoriatic Synovitis: Singularity and Potential Clinical Implications

  • Authors: R. Celis, A. Cuervo, J. Ramírez, J. Cañete
  • Year: 2019
  • Venue: Frontiers in Medicine
  • URL: https://www.semanticscholar.org/paper/1536df6b7385be85f1920e72ff6d8e69cc835206
  • DOI: 10.3389/fmed.2019.00014
  • PMID: 30805340
  • PMCID: 6378889
  • Citations: 37
  • Influential citations: 2
  • Summary: Modern methodologies, as MALDI-Mass Spectrometry Imaging, applied to the study of synovial tissue have revealed metabolic and lipid signatures which could support clinical decision-making in the diagnosis of PsA and RA and to go further toward the personalized medicine.
  • Evidence snippets:
  • Snippet 1 (score: 0.444) > Psoriatic arthritis (PsA) is an immuno-inflammatory disease with a heterogeneous clinical presentation as affects musculoskeletal tissues (arthritis, enthesitis, spondylitis), skin (psoriasis) and, less frequently, eye (uveitis) and bowel (inflammatory bowel disease). It has been suggested that distinct affected tissues could exhibit different immune-inflammatory pathways so complicating the understanding of the physiopathology of psoriatic disease as well as its treatment. Despite of the key pathogenic and clinical relevance that enthesitis has in PsA, peripheral arthritis is more easily perceived. At the macroscopic level, PsA synovitis has predominantly tortuous, bushy vessels, whereas rheumatoid arthritis (RA) is characterized by mainly straight, branching vessels so reflecting prominent neo-angiogenesis in PsA. Synovial biopsies have demonstrated a similar cellular and molecular picture in PsA and RA, although some differences have been reported at the group level, as higher density of vessels, CD163+ macrophages, neutrophils and mast cells in PsA. In fact, synovial IL-17+ mast cells are significantly increased in PsA and produce more IL-17A compared with RA, and a proof of concept study supports its relevant role in the synovitis of SpA, included PsA. As firstly reported in RA, synovial lymphoid neogenesis is found also in the same proportion of PsA as in RA patients, despite the lack of autoantibodies in PsA. These lymphoid structures are associated with activation of the IL-23/Th17 pathway in RA and seemly in PsA, which could be useful to stratify RA patients. Immunohistochemical and transcriptomic methodologies have still not found synovial biomarkers useful to distinguish psoriatic from rheumatoid synovitis at the patient level. However, modern methodologies, as MALDI-Mass Spectrometry Imaging, applied to the study of synovial tissue have revealed metabolic and lipid signatures which could support clinical decision-making in the diagnosis of PsA and RA and to go further toward the personalized medicine.

[15] Proteomics in Psoriasis

  • Authors: L. Chularojanamontri, Norramon Charoenpipatsin, N. Silpa‐archa, C. Wongpraparut, V. Thongboonkerd
  • Year: 2019
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/d2a4ace792f0c9cc650f5741e47dbaff5690738a
  • DOI: 10.3390/ijms20051141
  • PMID: 30845706
  • PMCID: 6429319
  • Citations: 26
  • Summary: This review summarizes and discusses all of the previous studies that applied various modalities of proteomics technologies to psoriatic skin disease and leads to novel mechanisms and new hypotheses of the disease pathogenesis.
  • Evidence snippets:
  • Snippet 1 (score: 0.443) > Psoriasis is a common, chronic, immune-mediated, inflammatory skin disease affecting humans worldwide with increasing prevalence and incidence, depending on geographical area [1]. The most common form is chronic plaque psoriasis, which is characterized by well-demarcated, erythematous plaques with silvery scales, accounting for approximately 85% of all psoriatic patients [2]. Although chronic plaque psoriasis can be found on all parts of the body, the most commonly affected areas include the elbows, knees, and scalp [3]. Psoriasis has been thought to be driven primarily by innate and adaptive immune systems that can be modified by genetic and environmental factors (e.g., alcohol, drugs, infections, skin trauma, smoking, and stress). The inflammatory cascade involves not only the skin but also other organs, leading to several comorbidities, e.g., psoriatic arthritis, metabolic syndrome (diabetes mellitus, hypertension, dyslipidemia, obesity, etc.), cardiovascular disease, non-alcoholic fatty liver disease, and kidney disorders [4]. Several lines of evidence have shown that T-cells, especially Th1 and Th17 cells, play crucial roles in such inflammatory responses [5]. However, antigen-antibody interactions also play important role, as demonstrated by the deposition of immunoglobulin G (IgG) and complement components in the upper epidermis of psoriatic skin [6]. Even with the aforementioned knowledge and advancements, the pathogenesis of psoriasis remains to be elucidated as there is a major part below the tip of the iceberg that is still covered, leading to unmet clinical needs [7]. In addition, current clinical practice in psoriasis for diagnostics, prognostics, and determination of the therapeutic outcome relies mainly on clinical findings and routine laboratory tests that frequently involve invasive procedures (i.e., skin and tissue biopsies) [7,8]. These limitations therefore warrant further investigations to better understand psoriatic pathogenesis and disease mechanisms, to define novel biomarkers for earlier and better diagnostics/prognostics, and to monitor treatment efficacy and drug-induced toxicities.

[16] Role of Recombinant Proteins for Treating Rheumatoid Arthritis

  • Authors: Mahboubeh Soleimani Sasani, Y. Moradi
  • Year: 2024
  • Venue: Avicenna Journal of Medical Biotechnology
  • URL: https://www.semanticscholar.org/paper/455e132608b909e67ea29486bb151fb6d4a3ef6c
  • DOI: 10.18502/ajmb.v16i3.15739
  • PMID: 39132628
  • PMCID: 11316508
  • Citations: 1
  • Summary: The genetic and immunological factors that influence the development of RA, recombinant proteins, methods of using these proteins, approved drugs, and side effects associated with treating RA are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.441) > Rheumatoid Arthritis (RA) is a chronic inflammatory disease that affects synovial joints and leads to pain, stiffness, and reduced mobility. Although the exact cause of this disease is not fully known, it appears to be an autoimmune disease in which the immune system mistakenly attacks the body's tissues. This problem is the result of a combination of genetic factors, the environment, and the immune system. RA is a complex disease involving both resident cells and infiltrating cells in membrane tissue 1 . In this disease, significant amounts of new vessels are formed in the membrane tissue, facilitating invasion by lymphocytes and monocytes and transforming a cell-free, loose cavity membrane into an abnormal, tumor-like invasive tissue. Micro vessels proliferate, forming straight vessels and branching regularly 1 . Studies have shown that the synovial fluid in patients with RA is highly inflamed in all joints and expresses much inflammatory genes 2 . The pathophysiology of RA is heterogeneous and includes defects in the innate and adaptive immune systems, genetic and environmental factors, autoantibodies, cellular changes, signaling pathways, and metabolism 1 . Understanding the role of individual variations in the cellular and molecular mechanisms associated with RA will significantly improve clinical care and patient outcomes. Individualized responses to standard therapy are observed in RA because of pathophysiological heterogeneity, ultimately leading to poor overall prognosis 2 . Key cellular and molecular findings in RA include angiogenesis, B cells, fibroblasts, reduced oxygen levels, synovial tissue, and T cells. Researchers are investigating altered metabolic pathways underlying synovial inflammation in RA 1 . The molecular and cellular heterogeneity of RA is a hot topic, and understanding the underlying mechanisms may lead to therapeutic intervention 3 . RA is currently treated worldwide to reduce inflammation, relieve pain, and slow the progression of joint damage. Conventional treatments include nonsteroidal anti-inflammatory drugs, diseasemodifying antirheumatic drugs, and biological agents, and in recent years, recombinant proteins have emerged as promising biological agents that can target specific proteins or cells involved in the inflammatory response 4 . Recombinant proteins are synthetic proteins that are produced in the laboratory using genetic engineering techniques.

[17] Case Report: Severe thrombocytopenia induced by adalimumab in rheumatoid arthritis: A case report and literature review

  • Authors: T. Liao, Mengqing Li, Tian Yuan, Qifu Hong, Yu Zeng et al.
  • Year: 2022
  • Venue: Frontiers in Pharmacology
  • URL: https://www.semanticscholar.org/paper/a544c421bc5d4e5b6c2672df1216d7b444304e2b
  • DOI: 10.3389/fphar.2022.1041884
  • PMID: 36386149
  • PMCID: 9640920
  • Citations: 5
  • Influential citations: 1
  • Summary: It is suggested immunoglobulins could be considered for the treatment of refractory thrombocytopenia in a patient with RA who was treated with adalimumab.
  • Evidence snippets:
  • Snippet 1 (score: 0.435) > Rheumatoid arthritis is a chronic systemic autoimmune illness that can cause joint discomfort, swelling and deformity. It is characterized by chronic synovial inflammatory reaction. The main pathological manifestations include synovial lining cell proliferation, interstitial inflammatory cell infiltration, microvascular neogenesis, pannus formation and cartilage and bone tissue destruction. It seriously affects the quality of life of the patients and multiple systems of the body. There are many molecular mechanisms in rheumatoid arthritis, such as the IL31/ IL33 axis, which leads to gene and protein activation of inflammatory diseases through cascade reactions (Murdaca et al., 2019). Subsequently involved in the secretion of TNF-α. Tumor necrosis factor is one of the major inflammatory cytokines in the RA patients. It regulates the production of inflammatory factor like IL-6, IL-8, MCP-1, and VEGF, as well as the recruitment of immune and inflammatory cells to the affected joint (Lim et al., 2018). Therefore, it plays an important role in the pathological development of RA. As a therapeutic target in rheumatoid arthritis, anti-TNF-α drugs have been used in the RA patients since mid-1990s. Numerous clinical studies have demonstrated that anti-TNF-α drugs can improve not only the clinical signs and symptoms of RA patients, but also their joint function and imaging results (Caporali et al., 2018). Anti-TNFα drugs were effective and were well tolerated by many RA patients. Multiple recommendations advocate the clinical use of anti-TNF-α drugs. 2021 American College of Rheumatology Guidelines recommend that patients who do not respond adequately to methotrexate monotherapy be considered for the addition of anti-TNF-α drugs (Fraenkel et al., 2021). In addition to RA, anti-TNF-α drugs are also used in the treatment of multiple autoimmune diseases, such as Crohn's disease, ulcerative colitis, psoriatic arthritis, etc. (Lim et al., 2018).

[18] Gene Profiling of a 3D Psoriatic Skin Model Enriched in T Cells: Downregulation of PTPRM Promotes Keratinocyte Proliferation through Excessive ERK1/2 Signaling

  • Authors: G. Rioux, F. Turgeon, G. Le-Bel, Camille Grenier, S. Guérin et al.
  • Year: 2022
  • Venue: Cells
  • URL: https://www.semanticscholar.org/paper/82bd7be1ba7527e36144a47f25d9e4b840b01b73
  • DOI: 10.3390/cells11182904
  • PMID: 36139479
  • PMCID: 9497242
  • Citations: 14
  • Summary: A tissue-engineered, two-layered human psoriatic skin substitute enriched in T cells may prove particularly useful in deciphering the mechanistic details of psoriasis pathogenesis and provide a relevant biomaterial for the study of potential therapeutic targets.
  • Evidence snippets:
  • Snippet 1 (score: 0.435) > Psoriasis is a complex, immune-mediated skin disease involving a wide range of epithelial and immune cells. The underlying mechanisms that govern the epidermal defects and immunological dysfunction observed in this condition remain largely unknown. In recent years, the emergence of new, more sophisticated models has allowed the evolution of our knowledge of the pathogenesis of psoriasis. The development of psoriatic skin biomaterials that more closely mimic native psoriatic skin provides advanced preclinical models that will prove relevant in predicting clinical outcomes. In this study, we used a tissue-engineered, two-layered (dermis and epidermis) human skin substitute enriched in T cells as a biomaterial to study both the cellular and molecular mechanisms involved in psoriasis’ pathogenesis. Gene profiling on microarrays revealed significant changes in the profile of genes expressed by the psoriatic skin substitutes compared with the healthy ones. Two genes, namely, PTPRM and NELL2, whose products influence the ERK1/2 signaling pathway have been identified as being deregulated in psoriatic substitutes. Deregulation of these genes supports excessive activation of the ERK1/2 pathway in psoriatic skin substitutes. Most importantly, electrophoresis mobility shift assays provided evidence that the DNA-binding properties of two downstream nuclear targets of ERK1/2, both the NF-κB and Sp1 transcription factors, are increased under psoriatic conditions. Moreover, the results obtained with the inhibition of RSK, a downstream effector of ERK1/2, supported the therapeutic potential of inhibiting this signaling pathway for psoriasis treatment. In conclusion, this two-layered human psoriatic skin substitute enriched in T cells may prove particularly useful in deciphering the mechanistic details of psoriatic pathogenesis and provide a relevant biomaterial for the study of potential therapeutic targets.

[19] Proteomic and Metabolomic Changes in Psoriasis Preclinical and Clinical Aspects

  • Authors: A. Radulska, I. Pelikant-Małecka, Kamila Jendernalik, I. Dobrucki, L. Kalinowski
  • Year: 2023
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/5d8553859955e0601b9f6259f05c75467ddce0c2
  • DOI: 10.3390/ijms24119507
  • PMID: 37298466
  • PMCID: 10253645
  • Citations: 12
  • Summary: Proteomics and metabolomics strategies and their utility in research and clinical practice in psoriasis and psoriatic arthritis are discussed and their contribution to the discovery of biomarkers and targets for biological drugs is highlighted.
  • Evidence snippets:
  • Snippet 1 (score: 0.434) > In the study 'Identification of New Prognostic Markers in Psoriatic Arthritis', the concentration of IL 17A and other cytokines was correlated with markers of bone remodeling, identifying the molecular pathways involved in psoriatic arthropathy. The progression of psoriasis leads to the development of many comorbidities other than psoriatic arthritis, such as metabolic syndrome and cardiovascular diseases [122]. The study 'Psoriasis Inflammation and Systemic Co Morbidities' was intended to explore the pathophysiology of psoriasis and its comorbidities, but it also provided guidance on how long-term treatment of inflammation can reduce or prevent cardiovascular events. > The next five selected clinical trials presented in Table 3 are currently recruiting patients for candidate biomarkers investigation to predict severity and responsiveness to treatment in psoriasis and psoriatic arthritis. These open-label trials are multicentered, and a large number of patients are planned to be enrolled. The smallest estimated number of participants is 50 patients in the 'An Explorative Psoriasis Biomarker Study', conducted in the Netherlands. The clinical trial requires fewer participants than others currently recruiting. However, it assumes a very wide breadth of its outcome. The study involves the analysis of various chemokines, cytokines, and immune cells in the blood and lesion and non-lesion skin, determination of skin and fecal microbiome, analysis of epidermal homeostasis and immune cell infiltration, measurement of skin surface biomarkers concentration and stratum lipidomic analysis of corneum and biopsy transcriptome.

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.