- Both atopic dermatitis (AD) and psoriasis are characterized by complex inflammatory circuits that may be regulated through “feed-forward” mechanisms in the epidermis that amplify cellular immune responses through production of keratinocyte-derived cytokines and inflammatory mediators. IL-17C is a unique cytokine that is produced by keratinocytes and that is involved in such synergistic loops that may be responsible for amplifying the inflammation in both diseases. This may ultimately lead to induction of S100As and other molecules that accompany epidermal hyperplasia.
- Psoriasis skin lesions are created through chronic T-cell activation and expansion of autoreactive, skin resident αβ T helper type 17 (Th17) cell clones (Matos et al., 2017), suggesting a defect in normal tolerance mechanisms. A previous study determined that although psoriasis patients have normal numbers of circulating regulatory T (Treg) cells (CD4+CD25+Foxp3+ T cells), psoriatic Treg cells were less effective at suppressing alloreactive T cells compared with Treg cells from healthy individuals (Bovenschen et al., 2011; de Boer et al., 2007; Sugiyama et al., 2005).
- Patients with psoriasis have an increased risk of myocardial infarction, and psoriasis is now recognized as an independent risk factor for coronary heart disease and cardiovascular mortality. To understand the effects of psoriasis medications on systemic inflammation associated with cardiovascular risks, we studied blood proteins related to inflammation and cardiovascular disease archived from a phase 3 clinical trial of tofacitinib and etanercept in adults with moderate-to-severe psoriasis. A total of 157 blood proteins were quantified by a proximity extension assay from 266 patients at baseline and week 4.
- We want to thank Hjuler et al. (2017) for their comments on our article (Bissonnette et al., 2017). We agree that many unknowns remain on the mechanisms of atherosclerosis in patients with psoriasis. Our hypothesis was that adalimumab reduced vascular inflammation in patients with moderate-to-severe psoriasis. Measurement of vascular inflammation in the aorta and the carotids did not confirm this hypothesis. The target-to-background ratio was measured in an area that was localized between the beginning of the ascending aorta and the left subclavian artery, which includes the ascending aorta and the aortic arch.
- Vascular inflammation is increased in patients with psoriasis. This randomized, double-blind, multicenter study evaluated the effects of tumor necrosis factor-α antagonist adalimumab on vascular inflammation in patients with psoriasis. A total of 107 patients were randomized (1:1) to receive adalimumab for 52 weeks or placebo for 16 weeks followed by adalimumab for 52 weeks. Vascular inflammation was assessed with positron emission tomography-computed tomography. There were no differences in the change from baseline in vessel wall target-to-background ratio (TBR) from the ascending aorta (primary endpoint) (adalimumab: TBR = 0.002, 95% confidence interval [CI] = –0.048 to 0.053; placebo: TBR = –0.002, 95% CI = –0.053 to 0.049; P = 0.916) and the carotids (adalimumab: TBR = 0.031, 95% CI = –0.005 to 0.066; placebo: TBR = 0.018, 95% CI = –0.019 to 0.055; P = 0.629) at week 16 between adalimumab and placebo.
- There is an “assessment gap” between the moment a patient’s response to treatment is biologically determined and when a response can actually be determined clinically. Patients’ biochemical profiles are a major determinant of clinical outcome for a given treatment. It is therefore feasible that molecular-level patient information could be used to decrease the assessment gap. Thanks to clinically accessible biopsy samples, high-quality molecular data for psoriasis patients are widely available. Psoriasis is therefore an excellent disease for testing the prospect of predicting treatment outcome from molecular data.
- Mild versus severe psoriasis is often distinguished by clinical measures such as the extent of skin involvement or Psoriasis Area and Severity Index score, both of which use arbitrary boundaries. It is widely assumed that severe psoriasis involves higher levels of skin inflammation, but comparative molecular profiles of mild versus severe disease have not been performed. In this study, we used immunohistochemistry, reverse transcription PCR, and gene arrays to determine the phenotype of North American patients with mild psoriasis (n = 34, mean PASI score = 5.5) versus severe psoriasis (n = 23, mean PASI score = 23.2).
- Psoriasis is present in all racial groups, but in varying frequencies and severity. Considering that small plaque psoriasis is specific to the Asian population and severe psoriasis is more predominant in the Western population, we defined Asian small and intermediate plaque psoriasis as psoriasis subtypes and compared their molecular signatures with the classic subtype of Western large plaque psoriasis. Two different characteristics of psoriatic spreading—vertical growth and radial expansion—were contrasted between subtypes, and genomic data were correlated to histologic and clinical measurements.