Combining Understanding of Immunological Mechanisms and Genetic Variants Toward Development of Personalized Medicine for Psoriasis Patients

Gunter, Natalie Vivien; Yap, Bryan Ju Min; Chua, Caroline Lin Lin; Yap, Wei Hsum

doi:10.3389/fgene.2019.00395

Cited by 19 publications

(10 citation statements)

References 99 publications

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“…[16] We develop the line of argumentation that supports this hypothesis and argue that this treatment strategy expands and optimises therapeutic options for a personalised medicine approach in the future management of psoriasis. [17,18]…”

Section: (B) (C)mentioning

confidence: 99%

Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis

Luengas‐Martinez

Hardman‐Smart

Paus

et al. 2020

Experimental Dermatology

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Vascular endothelial growth factor‐A (VEGF‐A), the main angiogenic mediator, plays a critical role in the pathogenesis of several inflammatory immune‐mediated diseases, including psoriasis. Even though anti‐angiogenic therapies, such as VEGF inhibitors, are licensed for the treatment of various cancers and eye disease, VEGF‐targeting interventions are not part of current psoriasis therapy. In this viewpoint essay, we argue that the existing preclinical research evidence on the role of VEGF‐A in the pathogenesis of psoriasis as well as clinical observations in patients who have experienced psoriasis remission during oncological anti‐VEGF‐A therapy strongly suggests to systematically explore angiogenesis targeting also in the management of psoriasis. We also point out that some psoriasis therapies decrease circulating levels of VEGF‐A and normalise the psoriasis‐associated vascular pathology in the papillary dermis of plaques of psoriasis and that a subset of patients with constitutionally high levels of VEGF‐A may benefit most from the anti‐angiogenic therapy we advocate here. Given that novel, well‐targeted personalised medicine therapies for the development of psoriasis need to be developed, we explore the hypothesis that VEGF‐A and signalling through its receptors constitute a promising target for therapeutic intervention in the future management of psoriasis.

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Section: (B) (C)mentioning

confidence: 99%

Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis

Luengas‐Martinez

Hardman‐Smart

Paus

et al. 2020

Experimental Dermatology

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“…have been many exciting developments in precision medicine approaches for autoimmune diseases (32,33). Our study demonstrated, for the first time, that precision medicine could potentially be applied to the treatment of GD.…”

Section: Discussionmentioning

confidence: 59%

Precision Medicine in Graves’ Disease: CD40 Gene Variants Predict Clinical Response to an Anti-CD40 Monoclonal Antibody

et al. 2021

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BackgroundCD40, a key co-stimulatory molecule expressed on antigen-presenting cells, is genetically associated with a number of autoimmune diseases including Graves’ disease (GD). Therefore, recent therapies targeting CD40 have been developed, including the anti-CD40 monoclonal antibody Iscalimab. In a recent pilot study, Iscalimab was shown to induce clinical remission in ~ 50% of GD patients, but the reason why only 50% of GD patients responded is not known. The aim of our study was to test the hypothesis that specific CD40 single nucleotide polymorphism (SNP) genotypes and haplotypes are associated with clinical response of GD patients to Iscalimab.MethodsWe extracted genomic DNA from the whole blood of 13 GD patients treated with Iscalimab, and genotyped seven CD40 single nucleotide polymorphisms (SNPs) associated with autoimmunity. Additionally, we analyzed CD40 mRNA expression levels in whole blood. The patients’ CD40 SNP genotypes and mRNA levels were tested for association with clinical response to Iscalimab.ResultsThree common haplotypes, designated haplotypes A, B, and C, were identified. Haplotypes B and C were associated with higher CD40 mRNA levels and clinical response to Iscalimab (i.e., patients achieving euthyroidism without need for additional medications), while haplotype A was associated with decreased CD40 mRNA levels and no response to Iscalimab.ConclusionOur data suggest that genetic polymorphisms in the CD40 gene drive its expression levels and response to Iscalimab. Polymorphisms associated with higher CD40 levels are also associated with clinical response to CD40-targeted therapies. These results set the stage to implementing precision medicine in the therapeutic approach to GD.

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“…We believe that a similar approach will prove extremely useful to better understand the pathogenesis of psoriasis, making it easier to find new therapeutic strategies for this disease. Data obtained from large-scale studies combined with individual genetic profiles will be extremely useful to define prognosis and develop personalized medicine for psoriasis patients [139].…”

Section: Discussionmentioning

confidence: 99%

The Brain–Skin Connection and the Pathogenesis of Psoriasis: A Review with a Focus on the Serotonergic System

Martins¹,

Ascenso²,

Ribeiro³

et al. 2020

Cells

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Psoriasis is a common non-communicable chronic immune-mediated skin disease, affecting approximately 125 million people in the world. Its pathogenesis results from a combination of genetic and environmental factors. The pathogenesis of psoriasis seems to be driven by the interaction between innate immune cells, adaptive immune cells and keratinocytes, in a process mediated by cytokines (including interleukins (IL)-6, IL-17 and IL-22, interferon and tumor necrosis factor) and other signaling molecules. This leads to an inflammatory process with increased proliferation of epidermal cells, neo-angiogenesis and infiltration of dendritic cells in the skin. Dysfunctional de novo glucocorticoid synthesis in psoriatic keratinocytes and the skin microbiome have also been suggested as mediators in the pathogenesis of this disease. To understand psoriasis, it is essential to comprehend the processes underlying the skin immunity and neuroendocrinology. This review paper focuses on the skin as a neuroendocrine organ and summarizes what is known about the skin immune system, the brain–skin connection and the role played by the serotonergic system in skin. Subsequently, the alterations of neuroimmune processes and of the serotonergic system in psoriatic skin are discussed, as well as, briefly, the genetic basis of psoriasis.

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Combining Understanding of Immunological Mechanisms and Genetic Variants Toward Development of Personalized Medicine for Psoriasis Patients

Cited by 19 publications

References 99 publications

Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis

Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis

Precision Medicine in Graves’ Disease: CD40 Gene Variants Predict Clinical Response to an Anti-CD40 Monoclonal Antibody

The Brain–Skin Connection and the Pathogenesis of Psoriasis: A Review with a Focus on the Serotonergic System

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