Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab

Mehta, Heena; Mashiko, Shunya; Angsana, Julianty; Rubio, Manuel; Hsieh, Ya-Ching M.; Maari, Catherine; Reich, Kristian; Blauvelt, Andrew; Bissonnette, Robert; Muñoz‐Elías, Ernesto J.; Sarfati, Marika

doi:10.1016/j.jid.2021.01.005

Cited by 83 publications

(93 citation statements)

References 60 publications

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“…In contrast, guselkumab decreased memory T cells while maintaining regulatory T cells, contrary to secukinumab. Neither drug modified the frequency of IL-17A + IL 17F +/− CD4 + or CD8 + T cells [ 30 ]. In the case of topical treatment, vitamin D analogues and corticosteroids reduce the lesional IL-17A-producing TRM, possibly also reducing pathogenic TRM [ 31 , 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Assessment of the Tissue Resident Memory Cells in Lesional Skin of Patients with Psoriasis and in Healthy Skin of Healthy Volunteers

Kasprowicz-Furmańczyk

Czerwińśka

Placek

et al. 2021

IJERPH

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Background: In the course of plaque psoriasis, tissue resident memory cells (TRM) are responsible for the phenomenon of “immune memory” of lesions, i.e., the appearance of recurrences of lesions in the same location, as well as Koebner phenomenon. We present results determining the location and amount of TRM in psoriatic lesions in patients suffering from plaque psoriasis, as well as an analysis of the relationship between TRM markers expression and the duration and severity of the disease. Methods: TRM markers (CD4, CD8, CD103, CD69, CD49, CXCR6) and tissue expression of cytokines (IL-17, IL-22) in the lesional psoriatic skin of 32 patients compared with 10 healthy skin samples were evaluated by immunohistochemistry. Results: The presence of TRM markers in both the epidermis and skin with psoriatic eruptions was demonstrated in much higher amounts compared with the skin of healthy volunteers. A significant positive relationship was demonstrated between the expression of TRM markers in patients with plaque psoriasis and the duration of skin lesions. There was no relationship between the amount of TRM and the severity of plaque psoriasis. Conclusions: A thorough understanding of the mechanisms responsible for the development and relapse of plaque psoriasis may contribute to the implementation of more effective therapies.

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Section: Discussionmentioning

confidence: 99%

Assessment of the Tissue Resident Memory Cells in Lesional Skin of Patients with Psoriasis and in Healthy Skin of Healthy Volunteers

Kasprowicz-Furmańczyk

Czerwińśka

Placek

et al. 2021

IJERPH

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“…Longitudinal study of tissue samples in a homogenous group of patients, as opposed to snapshot analysis in different cohorts, helps to identify potential pathogenic and regulatory cells, as well as key targets of treatments. Indeed, following the same psoriasis lesion before and during treatment at different time points strongly suggests that the major Infl Mo-like cells were the target of therapeutic cytokine blockade, underscoring their key role in disease pathogenesis (4).…”

Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

“…The authors further highlight the advantage of this molecular approach that identified 14 mononuclear phagocyte (MNP) cell states, and state that flow cytometry (FCM) has limitations to uncover diversity of rare cells. However, high dimensional single cell FCM is a complementary approach that has been proven suitable to reveal heterogeneity of skin MNP cell states in blood and skin (3,4).…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Skin Disorders: Monocyte-Derived Cells Take Center Stage

et al. 2021

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“…In biopsies obtained from psoriatic lesions, the majority of IL-17A-producing CD8 + T cells were T RM , whereas the majority of IL-17A-producing CD4 + T cells were non-T RM (defined as CD3 + /CD4 + /CD103 -/CD49 -T cells). 43 T reg display functional deficits in psoriasis T reg , which account for 5%-10% of skin resident T cells, sustain immune homeostasis and maintenance of selftolerance by suppressing inflammation, and specifically effector T cells. 44 T reg are characterised by high expression of Foxp3, a key transcription factor essential for their function, and IL-25, the IL-2 receptor alpha chain.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE)

et al. 2021

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BackgroundGuselkumab is an interleukin (IL)-23 pathway blocker with proven efficacy in patients with moderate-to-severe plaque psoriasis. Early intervention with guselkumab may result in changes to the clinical disease course versus later intervention.Methods and analysisHere we present the rationale and design of a phase 3b, randomised, double-blind, multicentre study (GUIDE), comparing treatment effects of guselkumab in patients with short (≤2 years) or longer (>2 years) duration of plaque-type psoriasis, measured from first appearance of psoriatic plaques. Participants achieving skin clearance (Psoriasis Area and Severity Index (PASI)=0) by week 20 and maintaining complete clearance at week 28 visit (‘super-responders’ (SRe)) will be randomised to continue approved maintenance dosing every 8 weeks (q8w) versus an investigational maintenance dosing interval of 16 weeks (q16w) until week 68. Primary endpoint: proportion of participants in the q8w vs q16w arms with absolute PASI <3 at week 68. Participants with PASI <3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks. Participants not achieving SRe criteria (non-SRe) will remain in the study with q8w guselkumab dosing through week 68. Additional to serum samples obtained from all patients, skin biopsies and whole-blood samples will be taken from SRe and non-SRe participants at various time points in optional substudies. Analyses include: genetics; immunophenotyping (fluorescence-activated cell sorting); gene and protein expression profiling; immunohistology. By merging clinical endpoints with mechanistic findings, this study aims to elucidate how IL-23 blockade with guselkumab can modify the disease course by altering molecular and cellular drivers that cause relapse after treatment withdrawal, particularly among SRe.Ethics and disseminationApproval obtained from ethics committee Medical Council Hamburg, Germany (PVN5925). GUIDE is compliant with the Declaration of Helsinki.Trial registration numberRegistered at ClinicalTrials.gov (NCT03818035). All primary endpoint results (prespecified analyses) will be submitted to peer-reviewed, international journals within 18 months after primary completion date.

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Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab

Cited by 83 publications

References 60 publications

Assessment of the Tissue Resident Memory Cells in Lesional Skin of Patients with Psoriasis and in Healthy Skin of Healthy Volunteers

Assessment of the Tissue Resident Memory Cells in Lesional Skin of Patients with Psoriasis and in Healthy Skin of Healthy Volunteers

Inflammatory Skin Disorders: Monocyte-Derived Cells Take Center Stage

IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE)

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