Complexities in Genetics of Psoriatic Arthritis

Rahmati, Sara; Tsoi, L.C.; O’Rielly, Darren D.; Chandran, Vinod; Rahman, Proton

doi:10.1007/s11926-020-0886-x

Cited by 23 publications

(16 citation statements)

References 41 publications

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“…It has been postulated that the initiation of PsA occurs after triggering by environmental factors in gut, entheses, or skin in patients who are genetically more susceptible to development of this disease (37). The genetics of PsA have been reviewed in detail (38)(39)(40)(41). In short, both HLA and non-HLA coding genes are associated with PsA.…”

Section: Initiation Of Psoriatic Arthritismentioning

confidence: 99%

“…HLA coding genes linked to PsA have supported the role for peptide binding and T cell activation in PsA pathogenesis (40). In the non-HLA coding groups genes are related to innate immunity, cytokines (TNF, IFN, and IL-23/17) and antigen processing and presentation (38). However, genes that are specifically associated with development of PsA in PsO patients remain scarce (39).…”

Section: Initiation Of Psoriatic Arthritismentioning

confidence: 99%

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Translational Research Studies Unraveling the Origins of Psoriatic Arthritis: Moving Beyond Skin and Joints

et al. 2021

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Patients with psoriatic arthritis (PsA) are suffering from a decreased quality of life despite currently available treatments. In the latest years, novel therapies targeting the IL-17/IL-23 and TNF pathways improved clinical outcome. Despite this, remission of disease is not achieved in a considerable group of patients, continuous treatment is very often required to reach clinical remission, and prevention of PsA in patients with psoriasis (PsO) is currently impossible. A better understanding of PsA pathogenesis is required to develop novel treatment strategies that target inflammation and destruction more effectively and at an early stage of the disease, or even before clinically manifest disease. The skin is considered as one of the sites of onset of immune activation, triggering the inflammatory cascade in PsA. PsO develops into PsA in 30% of the PsO patients. Influenced by environmental and genetic factors, the inflammatory process in the skin, entheses, and/or gut may evolve into synovial tissue inflammation, characterized by influx of immune cells. The exact role of the innate and adaptive immune cells in disease pathogenesis is not completely known. The involvement of activated IL-17A+ T cells could implicate early immunomodulatory events generated in lymphoid organs thereby shaping the pathogenic inflammatory response leading to disease. In this perspective article, we provide the reader with an overview of the current literature regarding the immunological changes observed during the earliest stages of PsA. Moreover, we will postulate future areas of translational research aimed at increasing our knowledge on the molecular mechanisms driving disease development, which will aid the identification of novel potential therapeutic targets to limit the progression of PsA.

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Section: Initiation Of Psoriatic Arthritismentioning

confidence: 99%

Section: Initiation Of Psoriatic Arthritismentioning

confidence: 99%

Translational Research Studies Unraveling the Origins of Psoriatic Arthritis: Moving Beyond Skin and Joints

et al. 2021

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“…The rapid emergence of affordable high-throughput technology will likely lead to the discovery of genetic factors that may lead to a more in-depth comprehension of mechanisms underlying the different phenotypical patterns of PsA and more precise profiling of axPsA patients. Such findings may hopefully support clinicians in choosing for each patient the treatment with higher likelihood efficacy (Rahmati et al, 2020 ).…”

Section: Discussionmentioning

confidence: 86%

“…Furthermore, although significant epidemiological clinical and prognostic differences between axPsA and ankylosing spondylitis (AS) have been highlighted in several studies (Jadon et al, 2017 ; Feld et al, 2018 ), it is still a matter of debate whether axPsA and AS are different phenotypes on the spectrum of the same disease, or they are different diseases with overlapping features (Feld et al, 2018 ). Genetic studies were called into question to understand the basis of such differences and overlapping aspects (Rahmati et al, 2020 ). In particular, the prevalence of HLA-B27, the key genetic marker of AS, was demonstrated to be lower in patients with PsA (20 vs. 95%), although among PsA patients, those with axPsA were significantly more frequently HLA-B27-positive compared with those without axial involvement ( P < 0.001).…”

Section: Introductionmentioning

confidence: 99%

Targeted Therapies in Axial Psoriatic Arthritis

et al. 2021

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Specific and high-quality evidence on the efficacy of the current targeted therapies for axial disease in psoriatic arthritis (axPsA) is still scarce. Indeed, almost all the cohorts investigated in clinical trials on PsA consisted of patients with peripheral arthritis, where a small number of them also had axial involvement. Only one randomized controlled trial was so far specifically designed to assess the efficacy of a biological disease-modifying antirheumatic drug (DMARD) in axPsA. For other biological and synthetic targeted DMARDs, the most specific evidence for treatment in axPsA is extrapolated from post-hoc analyses based on PsA patients with concomitant peripheral and axial manifestations. Furthermore, the current trials and post-hoc analysis on axPsA are affected by major limitations, including the lack of a widely accepted definition of axPsA and the lack of specific and validated outcome measures. Finally, poor data are available on the genetics of axPsA, although alleles differentially expressed in different patterns of axPsA might offer advantages in the prospective of personalized medicine in axPsA patients. Overall, this review suggests that there is an urgent need for more reliable evidence derived from studies specifically designed for axPsA and based on a validated definition of axPsA and on specific outcome measures.

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“…Psoriasis severity, psoriatic nail disease, infection, trauma, stress, and obesity are considered risk factors for the development of PsA; however, it remains unclear whether nail involvement is a predictor of PsA or an early manifestation of PsA [31]. Genetic studies have found PsA to have a strong genetic component [32][33][34] and have linked several human leukocyte antigen (HLA) genotypes to PsA (e.g., HLA-B*27) [35].…”

Section: Pathophysiology Of Psamentioning

confidence: 99%

Psoriatic arthritis: the role of the nonphysician clinician in the diagnosis and treatment of patients with psoriasis

Overcash

Chillura

Fender

et al. 2021

Drugs Ther Perspect

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Psoriatic arthritis is a clinically heterogeneous, chronic, and progressive disease that develops in up to 30% of patients with psoriasis and is characterized by multiple and increasing joint defects caused by persistent immune-mediated inflammation. Several treatment options are available, including multiple biologic agents that inhibit specific cellular mediators of inflammation either directly or indirectly. Early detection and intervention are critical to preventing severe joint damage and pain, necessitating increased awareness and education about this disease for primary providers and nonphysician clinicians. Physician assistants and nurse practitioners, given their role in the primary care setting and within multiple specialty areas such as dermatology and rheumatology, are often the first to see patients who may have psoriatic arthritis. These healthcare providers are increasingly important in the early diagnosis and treatment of this disease. In this review, we provide an overview of psoriasis and psoriatic arthritis and discuss the multiple treatment options that are available for these patients. We also discuss ways to help recognize early joint involvement in the clinic and emphasize the role that nonphysician clinicians play in the care of patients with psoriatic arthritis. Key points Psoriatic arthritis, an inflammatory disease, may cause irreversible joint damage in patients with psoriasis. Physician assistants and nurse practitioners in dermatology and rheumatology, who are well positioned to recognize psoriatic arthritis early, treat patients, and prevent long-term complications, benefit from education on recognizing and treating psoriatic disease to improve outcomes. Biologics have demonstrated efficacy in several disease domains of psoriatic arthritis, and treatment guidelines generally recommend their use over that of nonbiologic agents.

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Complexities in Genetics of Psoriatic Arthritis

Cited by 23 publications

References 41 publications

Translational Research Studies Unraveling the Origins of Psoriatic Arthritis: Moving Beyond Skin and Joints

Translational Research Studies Unraveling the Origins of Psoriatic Arthritis: Moving Beyond Skin and Joints

Targeted Therapies in Axial Psoriatic Arthritis

Psoriatic arthritis: the role of the nonphysician clinician in the diagnosis and treatment of patients with psoriasis

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