The mechanistic basis for psoriasis immunopathogenesis: translating genotype to phenotype. Report of a workshop, Venice, 2012

Abstract

The International Psoriasis Council, a global nonprofit organization dedicated to advancing psoriasis research and treatment, led an initiative to better define the pathogenic mechanisms that constitute psoriasis. In September 2012, a workshop was held at the 42nd Annual European Society for Dermatological Research in Venice, Italy. By assembling a panel of global dermatology and immunology experts, the objective was to evaluate the current status of the science explaining the mechanism of disease in psoriasis, e.g. dysregulation of the skin immune system and perturbations of epidermal homeostasis. The workshop consisted of four oral presentations, which addressed key topics in psoriasis, delivered by Hervé Bachelez (Paris, France), Antonio Costanzo (Rome, Italy), Michelle Lowes (New York, NY, U.S.A.) and Frank Nestle (London, U.K.). A global expert panel was assembled to stimulate dialogue and debate: Kevin Cooper (Cleveland, OH, U.S.A.), Michel Gilliet (Lausanne, Switzerland), Joerg Prinz (Munich, Germany), Martin Röcken (Tubingen, Germany), Jens Schroeder (Kiel, Germany), Manuelle Viguier (Paris, France), Mayte Suárez-Fariñas (New York, NY, U.S.A.) and Cristina Zielinski (Berlin, Germany). Collectively, the presentations demonstrated the significant advances in understanding immune regulation that have occurred over the past decade by virtue of the study of psoriasis subtypes, phenotypic manifestations and genetic associations. Elucidating the pathogenic and genetic basis of psoriasis holds the promise of a complete understanding of disease mechanisms, predictors of treatment response, novel drug development strategies and customized therapeutic regimens for the individual patient.

Generalised fibrotic gingival enlargement in a psoriatic patient: an association or a coincidence?

“…Fibroblasts from psoriatic skin but not from normal skin can induce hyperproliferation of normal keratinocytes. Fibroblasts from uninvolved psoriatic skin proliferate faster than normal fibroblasts in the presence of normal human serum and proliferate to an even greater extent in the presence of serum from psoriatic patients 18. This evidence supported our assumption about the possible T-lymphocyte stimulation in our patient, which induced fibroblasts to cause epidermal hyperproliferation, resulting in increased collagen production in gingiva leading to gingival hyperplasia 12.…”

Cellular dissection of psoriasis for transcriptome analyses and the post-GWAS era

“…To better understand molecular mechanisms underlying this process, investigators have applied genome-scale technologies, such as expression profiling and genome-wide association studies (GWAS) [1-4]. This has provided a wealth of new data, although there remain many gaps between the individual genes uncovered from these approaches and our current understanding of psoriasis pathogenesis [5]. In this respect, a key challenge is that both approaches, expression profiling and GWAS, essentially provide pointers to individual genes, but do not necessarily provide indication as to which cell type serves as the main context for a gene’s disease activity [3,6-8].…”

Association of the Psoriatic Microenvironment With Treatment Response

“…After a patient commences a psoriasis therapy, there is often a delay of weeks to months between the earliest detectable tissue response in skin biopsy samples and the earliest point where a significant clinical response can be seen (defined as a 75% reduction in the Psoriasis Area and Severity Index [PASI] score [PASI75] was defined as clinical response). 23,24 This gap may result in patients spending long periods of time using treatments that may not be effective for them, thereby increasing financial burden, risk of adverse events, and disease progression. [25][26][27][28] This gap also elevates drug development costs in research trials.…”