Biologic insights from single-cell studies of psoriasis and psoriatic arthritis

Jin, Julia; Wu, David; Spencer, Riley; Elhage, Kareem; Liu, Jared; Davis, Mitchell S.; Hakimi, Marwa; Kumar, Satish; Huang, Zhiming; Bhutani, Tina; Liao, Wilson

doi:10.1080/14712598.2022.2142465

Cited by 4 publications

(5 citation statements)

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“…To better understand the diseases as systemic changes affecting the entire organism, modern methods addressing molecular and cellular mechanisms at the level of single cells could carry us forward. 97 For example, this could also help to better understand the links between psoriasis and components of the central and peripheral nervous system, which have not been well studied so far. 98 Thus, the important question arises whether the use of antipsoriatic medication should be based only on the severity of psoriasis or also on the comorbidity profile.…”

Section: Where Are We Going?mentioning

confidence: 99%

“…Associations of psoriasis with other diseases, especially other chronic inflammatory diseases, are still largely based on empirical and epidemiological studies. To better understand the diseases as systemic changes affecting the entire organism, modern methods addressing molecular and cellular mechanisms at the level of single cells could carry us forward 97 . For example, this could also help to better understand the links between psoriasis and components of the central and peripheral nervous system, which have not been well studied so far 98 .…”

Section: Where Are We Going?mentioning

confidence: 99%

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Current developments and perspectives in psoriasis

Schön

Wilsmann‐Theis

2023

J Deutsche Derma Gesell

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The study of psoriasis has yielded fundamental new insights into immunologic regulation and innovative therapies in a way that few other diseases have. In this review, we summarize the main features of current psoriasis research with emphasis on pathophysiological processes and the milestones in the approval of various biologics and small molecule drugs. Thus, through psoriasis research, we are gaining a better understanding of the interplay between the components of the innate and adaptive immune systems. New therapeutics interfere with crucial regulatory networks. Based on current knowledge, we outline what we believe to be some of the most important future research directions and therapeutic and clinical developments in psoriasis. These span multiple areas, ranging from the study of genetic, epigenetic, cellular, and immunological mechanisms to studies of particular clinical forms of psoriasis, individual systemic effects of the disease and its treatment, and the incorporation of large connected data sets and artificial intelligence. The goal is to understand psoriasis holistically, from the molecular to the organismic and societal levels, in order to develop individualized prevention and treatment strategies. Despite impressive progress, psoriasis research must continue to evolve at both the smallest and largest scales to comprehensively address the needs of both physicians and patients.

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Section: Where Are We Going?mentioning

confidence: 99%

Section: Where Are We Going?mentioning

confidence: 99%

Current developments and perspectives in psoriasis

Schön

Wilsmann‐Theis

2023

J Deutsche Derma Gesell

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“…Um die Krankheiten als systemische Veränderungen, die den gesamten Organismus beeinflussen, besser zu verstehen, könnten moderne Methoden, die molekulare und zelluläre Mechanismen auf der Ebene einzelner Zellen adressieren, weiterführen. 97 Beispielsweise könnten so auch die bislang noch nicht gut untersuchten Zusammenhänge zwischen Psoriasis und Komponenten des zentralen und peripheren Nervensystems besser verstanden werden. 98 Es kommt somit die wichtige Frage auf, ob der Einsatz der antipsoriatischen Medikation sich nur nach dem Schweregrad der Psoriasis richten sollte oder auch nach dem Komorbiditätsprofil.…”

Section: Wohin Gehen Wir?unclassified

“…Zusammenhänge der Psoriasis mit anderen Krankheiten, insbesondere anderen chronisch‐entzündlichen Krankheiten, basieren noch weitgehend auf empirischen und epidemiologischen Untersuchungen. Um die Krankheiten als systemische Veränderungen, die den gesamten Organismus beeinflussen, besser zu verstehen, könnten moderne Methoden, die molekulare und zelluläre Mechanismen auf der Ebene einzelner Zellen adressieren, weiterführen 97 . Beispielsweise könnten so auch die bislang noch nicht gut untersuchten Zusammenhänge zwischen Psoriasis und Komponenten des zentralen und peripheren Nervensystems besser verstanden werden 98 .…”

Section: Wohin Gehen Wir?unclassified

Aktuelle Entwicklungen und Perspektiven bei Psoriasis

Schön

Wilsmann‐Theis

2023

J Deutsche Derma Gesell

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ZusammenfassungDie Erforschung kaum einer anderen Erkrankung hat so grundlegend neue Erkenntnisse über immunologischen Regulationen und gleichzeitig eine derart rasante Entwicklung innovativer Therapien hervorgebracht wie das Studium der Psoriasis. In dieser kurzen Übersichtsarbeit umreißen wir die Grundzüge der aktuellen Psoriasisforschung unter besonderer Berücksichtigung pathophysiologischer Vorgänge und der Meilensteine bei der Zulassung verschiedener Biologika und niedermolekularer Pharmaka. Nicht zuletzt durch die Psoriasisforschung verstehen wir das Zusammenspiel der Komponenten des angeborenen und des adaptiven Immunsystems immer besser. Neue Therapeutika greifen dabei an entscheidenden Punkten in regulatorische Netzwerke ein. Ausgehend vom derzeitigen Kenntnisstand skizzieren wir einige aus unserer Sicht wesentliche zukünftige Forschungsrichtungen sowie therapeutische und klinische Entwicklungen im Bereich der Psoriasis. Diese reichen von der Erforschung genetischer, epigenetischer, zellulärer und immunologischer Mechanismen über die Untersuchung spezifischer klinischer Formen der Psoriasis und individueller systemischer Auswirkungen der Krankheit sowie ihrer Behandlung bis hin zur Einbeziehung von Big Data und künstlicher Intelligenz. Ziele sind ein ganzheitliches Verständnis der Psoriasis von der molekularen bis zur organismischen und gesellschaftlichen Ebene und darauf aufbauend individualisierte Präventions‐ und Behandlungsstrategien. Trotz beeindruckender Fortschritte muss die Psoriasisforschung sowohl im kleinen als auch im großen Maßstab weiterentwickelt werden, um den Bedürfnissen von Behandlern und Patienten noch besser gerecht zu werden.

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“…The pathogenesis of psoriasis is characterized by dysregulation of the IL-17/23 axis and of various cell types including T-cells, dendritic cells, keratinocytes, and stromal cells (11). The genetic contribution to psoriasis susceptibility has been estimated to be about 70% (12).…”

Section: Introductionmentioning

confidence: 99%

A partitioned polygenic risk score reveals distinct contributions to psoriasis clinical phenotypes across a multi-racial cohort

Orcales,

Kumar,

Bui

et al. 2024

Preprint

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Psoriasis is a chronic, immune-mediated inflammatory skin disease associated with a polygenic mode of inheritance. There are few studies that explore the association of a psoriasis Polygenic Risk Score (PRS) with patient clinical characteristics, and to our knowledge there are no studies examining psoriasis PRS associations across different races. In this study, we used a multi-racial psoriasis cohort to investigate PRS associations with clinical phenotypes including age of onset, psoriatic arthritis, other comorbidities, psoriasis body location, psoriasis subtype, environmental triggers, and response to therapies. We collected patient data and Affymetrix genome-wide SNP data from a cohort of 607 psoriasis patients and calculated an 88-loci PRS (PRS-ALL), also partitioned between genetic loci within the HLA region (PRS-HLA; 11 SNPS) and loci outside the HLA region (PRS-NoHLA; 77 SNPS). We used t-test and logistic regression to analyze the association of PRS with clinical phenotypes. We found that PRS-HLA and PRS-noHLA had differing effects on psoriasis age of onset, psoriatic arthritis, psoriasis located on the ears, genitals, nails, soles of feet, skin folds, and palms, skin injury as an environmental trigger, cardiovascular comorbidities, and response to phototherapy. In some cases these PRS associations were race specific. Overall, these results show that the genetic basis for clinical manifestations of psoriasis are driven by distinct HLA and non-HLA effects, and that these PRS associations can be dependent on race.

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Biologic insights from single-cell studies of psoriasis and psoriatic arthritis

Cited by 4 publications

References 71 publications

Current developments and perspectives in psoriasis

Current developments and perspectives in psoriasis

Aktuelle Entwicklungen und Perspektiven bei Psoriasis

A partitioned polygenic risk score reveals distinct contributions to psoriasis clinical phenotypes across a multi-racial cohort

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