Psoriatic arthritis and gene therapy

Rheumatoid and psoriatic arthritis (RA and PsA) are inflammatory rheumatic disorders characterised by a multifactorial etiology. To date, the genetic contributions to the disease onset, severity and drug response are not clearly defined, and despite the development of novel targeted therapies, ~10% of patients still display poor treatment responses. We characterised a selected cohort of eleven non-responder patients aiming to define the genetic contribution to drug resistance. An accurate clinical examination of the patients was coupled with several high-throughput genetic testing, including HLA typing, SNPs-array and Whole Exome Sequencing (WES)...

Psoriatic arthritis (PsA) is a heterogeneous chronic musculoskeletal disease, affecting up to 30% of people with psoriasis. Research into PsA pathogenesis has led to the development of targeted therapies, including Tumor Necrosis Factor inhibitors (TNF-i). Good response is only achieved by ~60% of patients leading to 'trial and error' drug management approaches, adverse reactions and increasing healthcare costs. Robust and well-validated biomarker identification, and subsequent development of sensitive and specific assays, would facilitate the implementation of a stratified approach into clinical care...

BACKGROUND: Clinical characteristics and manifestations of psoriatic arthritis (PsA) have been extensively studied in western countries, yet data of Korean patients with PsA are very limited. We aimed to investigate the clinical traits of patients with PsA and dissect the characteristics of those with axial involvement. METHODS: In this observational study, we analyzed clinical data of 109 patients with PsA who were enrolled in the Korean College of Rheumatology Biologics and Targeted Therapy registry between December 2012 and March 2022 at the time point of initiating or switching to a biologic agent...

Psoriatic arthritis (PsA) is a chronic inflammatory rheumatic disease. The introduction of therapy with biological drugs is promising, even if the efficacy is very variable. Since the response to drugs is a complex trait, identifying genetic factors associated to treatment response could help define new biomarkers for a more effective and personalized therapy. This study aimed to evaluate the potential role of polymorphisms in genes involved in PsA susceptibility as predictors of therapy efficacy. Nine polymorphisms were analyzed in a cohort of 163 PsA patients treated with TNF-i...

BACKGROUND: MAP kinases are some of the cascades that are specialized in the cell's response to external stimuli. Their impaired functioning can be observed during the course of psoriatic arthritis. Currently, the best-known class of biological drugs is the inhibitors of the proinflammatory cytokine TNF-α, including adalimumab. OBJECTIVE: The aim of this study was to assess changes in the expression of MAP kinase genes in patients with psoriatic arthritis treated with adalimumab, as well as to determine which of the analyzed transcripts could be used as a diagnostic or therapeutic target...

Background: Despite numerous genome-wide association studies conducted in psoriasis and psoriatic arthritis, only a small fraction of the identified genes has been therapeutically targeted. Objective: We sought to identify and analyze potential therapeutic targets for psoriasis and psoriatic arthritis (PsA) using the priority index (Pi), a genetics-dependent drug target prioritization approach. Methods: Significant genetic variants from GWAS for psoriasis, PsA, and combined psoriatic disease were annotated and run through the Pi pipeline...

INTRODUCTION: We aimed to compare demographics and clinical characteristics between patients with inflammatory arthritis (IA) with vs. without neutralizing anti-drug antibodies (nADAb) against tumor necrosis factor inhibitors (TNFi). A secondary aim of the study was to explore if current smokers were more frequently nADAb-positive. METHODS: TNFi-treated outpatients with IA were recruited and a broad range of disease activity measures were assessed. nADAb were assessed using a reporter gene assay...

Regulatory T cells (Tregs) comprise a CD4+ CD25+ Foxp3+ T cell subset for maintaining immune tolerance, and their deficits and/or dysfunction are observed in autoimmune diseases. The lymphocyte activation gene 3 (LAG-3, also known as CD223), which is an immunoglobulin superfamily member expressed on peripheral immune cells, is recognized as an inhibitory regulator of Tregs. LAG-3+ T cells represent a novel protective Tregs subset that produces interleukin-10. Alterations in LAG-3+ Tregs have been reported in several autoimmune diseases, suggesting their potential pathogenic role...

Approximately 20-40% of patients with inflammatory bowel disease (IBD) are obese. Obesity is associated with inferior outcomes in patients with IBD, with lower rates of achieving remission, poor quality of life, and higher burden of unplanned healthcare utilization. Multiple cohort studies in patients with immune-mediated inflammatory diseases, including IBD, treated with biologic agents like tumor necrosis factor-α antagonists have suggested that obesity is associated with inferior response to biologic therapy...

Dermatologic diseases are the fourth most frequent nonfatal common illness, yet they have a psychological, economical, and professional burden that is comparable to or larger than other chronic conditions. From a survey in China of 6 provinces, the overall prevalence of psoriasis with squamous cell carcinoma was 0.47%. According to the current investigation, the outburst of skin disease was not associated with gender, but mainly with the climate of the environment; that is, dry cold weather will more likely to induce psoriasis...

Pharmacogenomic studies allowed the reasons behind the different responses to treatments to be understood. Its clinical utility, in fact, is demonstrated by the reduction in adverse drug reaction incidence and the improvement of drug efficacy. Pharmacogenomics is an important tool that is able to improve the drug therapy of different disorders. In particular, this review will highlight the current pharmacogenomics knowledge about biologics and small-molecule treatments for psoriasis. To date, studies performed on genes involved in the metabolism of biological drugs (tumor necrosis factor inhibitors and cytokines inhibitors) and small molecules (apremilast, dimethyl fumarate, and tofacitinib) have provided conflicting results, and further investigations are necessary in order to establish a set of biomarkers to be introduced into clinical practice...

The major challenge in the treatment of autoimmune diseases is the restoration of the impaired peripheral immune tolerance that always accompanies the development of such diseases. Here, we show that small splenic peptides (SSPs) of whole spleen extract efficiently suppress the development of psoriatic arthritis in vivo, even in the presence of sustained levels of pro-inflammatory cytokines. SSPs target dendritic cells (DCs) and convert them into tolerogenic cells, which in turn differentiate naive CD4+ cells into Foxp3-expressing T regulatory cells (Tregs)...

Paradoxical reaction (PR) occurs when a drug elicits a reaction contrary to what was expected. To clarify the clinical features and genetic background of individuals susceptible to PR, we analyzed the clinical course of patients in whom psoriatic eruptions worsened or newly developed during tumor necrosis factor (TNF) antagonist administration and the role of focal infections and genetic variations. Of 125 patients who received TNF antagonist therapy for psoriasis, acrodermatitis continua of Hallopeau (ACH), generalized pustular psoriasis (GPP), or palmoplantar pustular psoriasis (PPP), eight patients with PR were surveyed at our hospital Dermatology Department between 2010 and 2021...

Introduction: One of the examples of genes whose expression can be altered by the action of ustekinumab is TGF-β. It is a pleiotropic cytokine whose activity affects psoriatic changes and the state of homeostasis of the whole organism. Aim: To evaluate the effect of ustekinumab on the transcriptional activity of TGF-β family genes in patients with psoriatic arthritis and to check whether the results obtained can be helpful in monitoring the progress of treatment...

The seronegative spondyloarthropathies are a group of autoimmune inflammatory diseases lacking rheumatoid factor or antinuclear antibody in their serum. They include ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis, spondylitis associated with Crohn's disease and ulcerative colitis, and undifferentiated spondyloarthropathies. Inflammation mostly affects the axial joints, entheses, and extra-articular structures such as uveal tract, gastrointestinal tract, mucocutaneous tissue, and heart...

Objective: Rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) belong to inflammatory rheumatic diseases, the group of conditions of unknown etiology. However, a strong genetic component in their pathogenesis has been well established. A dysregulation of cytokine networks plays an important role in the development of inflammatory arthritis. Interleukin 33 (IL-33) is a recently identified member of the IL-1 family. To date, the significance of IL-33 in inflammatory arthritis has been poorly studied...

BACKGROUND: Tofacitinib is a novel Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. In clinical trials, the most common adverse events observed were nasopharyngitis, upper respiratory tract infections, and zoster. JAKs are found downstream of the type II cytokine receptor family used by a number of TH 17 cell-associated cytokines for signal transduction. These cytokines lead to the secretion of antiviral and antimicrobial peptides (AMPs) by keratinocytes or synoviocytes...

AIMS: The ability to predict response to treatment remains a key unmet need in psoriatic disease. We conducted a systematic review of studies relating to biomarkers associated with response to treatment in either psoriasis vulgaris (PsV) or psoriatic arthritis (PsA). METHODS: A search was conducted in PubMed, Embase and the Cochrane library from their inception to 2 September 2020, and conference proceedings from four major rheumatology conferences. Original research articles studying pre-treatment biomarker levels associated with subsequent response to pharmacologic treatment in either PsV or PsA were included...

Background: Undifferentiated arthritis (UA) is defined as an inflammatory arthritis that does not fulfill criteria for a definite diagnosis. Delay in reaching a specific diagnostic and therapy may lead to impaired functional outcomes. Our aim was to identify synovial biomarkers associated with definitive diagnostic classification in patients with UA. Methods: DMARD-naïve UA patients with available initial synovial tissue (ST) and a final diagnosis of rheumatoid arthritis (RA) or psoriatic arthritis (PsA) during follow-up were included and compared with patients with well-defined disease (RA or PsA)...

IMPORTANCE: Psoriasis is a heterogeneous disease. Improved understanding of prognosis and long-term outcomes in new-onset psoriasis may improve care. OBJECTIVE: To describe the clinical course of psoriasis and identify possible indicators of long-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: The Stockholm Psoriasis Cohort was a noninterventional inception cohort study enrolling patients between 2001 and 2005. The present study was conducted from January 15, 2019, to February 5, 2021...