Five Functional Aspects of the Epidermal Barrier Lefèvre-Utile, Alain; Braun, Camille; Haftek, Marek ...
International journal of molecular sciences,
10/2021, Volume:
22, Issue:
21
Journal Article
Peer reviewed
Open access
The epidermis is a living, multilayered barrier with five functional levels, including a physical, a chemical, a microbial, a neuronal, and an immune level. Altogether, this complex organ contributes ...to protect the host from external aggression and to preserve its integrity. In this review, we focused on the different functional aspects.
Psoriasis (PsO) and psoriatic arthritis (PsA), together known as psoriatic disease (PsD), are immune-mediated diseases with a chronic and relapsing course that affect the skin, the joints or both. ...The pathophysiology of PsO is complex and involves abnormal expression of keratinocytes and infiltration of the skin with dendritic cells, macrophages, neutrophils and T lymphocytes. Around 30% of patients with PsO develop arthritis with axial and/or peripheral manifestations. Both PsO and PsA share similar Th1- and Th17-driven inflammation, with increased production of inflammatory cytokines, including TNFα, IFN-γ, IL-17, IL-22, IL-23 in the skin and the synovial membrane. PsD is associated with a high burden of cardiometabolic diseases such as hypertension, diabetes, dyslipidemia, obesity, metabolic syndrome and cardiovascular (CV) complications as compared to the general population. These comorbidities share common immunopathogenic pathways linked to systemic inflammation, and are associated with the extent and severity of the disease. Morever, they can influence treatment outcomes in PsD. In this short review, we summarize the available evidence on the epidemiology, clinical aspects and mechanisms of cardiometabolic conditions in patients with PsD. We also discuss the impact of targeted treatments such as methotrexate and biological agents on these cardiometabolic conditions.
In the era of immunotherapies there is an urgent need to implement the use of circulating biomarkers in clinical practice to facilitate personalized therapy and to predict treatment response. We ...conducted a prospective study to evaluate the usefulness of circulating exosomal-PD-L1 in melanoma patients' follow-up. We studied the dynamics of exosomal-PD-L1 from 100 melanoma patients by using an enzyme-linked immunosorbent assay. We found that PD-L1 was secreted through exosomes by melanoma cells. Exosomes carrying PD-L1 had immunosuppressive properties since they were as efficient as the cancer cell from which they derive at inhibiting T-cell activation. In plasma from melanoma patients, the level of PD-L1 (n= 30, median 64.26 pg/mL) was significantly higher in exosomes compared to soluble PD-L1 (n= 30, 0.1 pg/mL). Furthermore, exosomal-PD-L1 was detected in all patients whereas only 67% of tumour biopsies were PD-L1 positive. Although baseline exosomal-PD-L1 levels were not associated with clinic-pathologic characteristics, their variations after the cures (ΔExoPD-L1) correlated with the tumour response to treatment. A ΔExoPD-L1 cut-off of> 100 was defined, yielding an 83% sensitivity, a 70% specificity, a 91% positive predictive value and 54% negative predictive values for disease progression. The use of the cut-off allowed stratification in two groups of patients statistically different concerning overall survival and progression-free survival. PD-L1 levels in circulating exosomes seem to be a more reliable marker than PD-L1 expression in tumour biopsies. Monitoring of circulating exosomal-PD-L1 may be useful to predict the tumour response to treatment and clinical outcome.
Due to the increasing evidence of their health benefits, whole grains are recommended for consumption worldwide. Such recommendations are, however, rarely quantitative. Our aim was to perform a ...quantitative evaluation of the relationship between whole grain consumption and the occurrence of type 2 diabetes (T2D) to support a recommendation on the daily consumption of whole grains.
We conducted a systematic review by searching three bibliographic databases. We included human studies addressing the relationship between whole grain consumption and T2D occurrence, and providing quantitative information on daily intake of whole grains. A dose-response meta-regression analysis between whole grain intake and T2D occurrence was performed, using a hierarchical mixed least square linear regression model. Eight observational studies were included (all but one prospective), with a total of 15,573 cases of T2D among 316,051 participants. Quantitative meta-regression demonstrated a significant linear inverse relationship between whole grain intake and T2D occurrence (P<0.0001), with an overall absolute reduction of 0.3% in the T2D rate for each additional 10 g of whole grain ingredient consumed daily. The association persisted when adjusted on sex, age, country, study design, follow up duration, and mode of report of whole grain intakes (as foods or ingredients).
The meta-regression model made it possible to estimate the decrease in T2D risk corresponding to various changes in whole grain intakes, and the results contribute to setting up quantitative recommendations. For instance, consuming three servings of whole grain foods (45 g of whole grain ingredients) daily would induce a 20% relative reduction in the T2D risk as compared to consuming a half serving (7.5 g of whole grain ingredients). These results should be considered for future recommendations, by considering the actual whole grain intake of the concerned populations. The systematic review protocol was published on the PROSPERO register (CRD42013006925).
Paradoxical adverse events (PAEs) have been reported during biological treatment for chronic immune-mediated diseases. PAEs are defined as the occurrence during biological agent therapy of a ...pathological condition that usually responds to this class of drug. A wide range of PAEs have been reported including dermatological, intestinal and ophthalmic conditions, mainly with antitumour necrosis factor α (TNF-α) agents. True PAEs include psoriasis, Crohn's disease and hidradenitis suppurativa. Other PAEs may be qualified as borderline and include uveitis, scleritis, sarcoidosis and other granulomatous diseases (granuloma annulare, interstitial granulomatous dermatitis), vasculitis, vitiligo and alopecia areata. Proposed hypotheses to explain these PAEs include an imbalance in cytokine production, the differential immunological properties between the monoclonal antibodies and TNF-α soluble receptor, an unopposed type I interferon production and a shift towards a Th1/Th2 profile. Data from registries suggest that the risk for paradoxical psoriasis is low and non-significant. We discuss management of these PAEs, which depends on the type and severity of the adverse events, pre-existing treated conditions and the possibility of alternative therapeutic options for the underlying disease. Paradoxical adverse events are not restricted to anti-TNF-α agents and close surveillance of new available biological drugs (anti-interleukin-17/23, anti-integrin) is warranted in order to detect the occurrence of new or as yet undescribed events.
Background Skin psoriasis precedes the onset of psoriatic arthritis (PsA) in 84% of patients with psoriasis. Dermatologists have an important role to screen psoriasis patients for PsA. The efficiency ...of PsA screening remains unknown. Objective We sought to determine the point prevalence of undiagnosed PsA in patients with psoriasis using a systematic search of the literature and meta-analysis. Methods PubMed, Cochrane, and Embase database searches yielded 394 studies for review. No study aimed to determine the prevalence of undiagnosed PsA in patients with psoriasis. We assumed that the prevalence of newly diagnosed PsA in patients with psoriasis at the time they seek medical care could be a sound estimate of this value. Seven epidemiological studies and 5 studies on PsA screening questionnaires allowed us to clearly identify patients with newly diagnosed PsA and were selected for review. Results The prevalence of undiagnosed PsA was 15.5% when all studies were considered and 10.1% when only epidemiological studies were considered. Limitations Data were obtained from studies not designed to address the question at hand. Heterogeneity was high ( I2 = 96.86%), and therefore a random effects model was used. Conclusion The high prevalence of undiagnosed PsA in patients with psoriasis adds to the recommendation that dermatologists need to screen all patients with psoriasis for PsA.
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