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Background The effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response. Objectives We aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohort. Methods We investigated the copy number variation in the LCE3B and LCE3C genes, and eight single-nucleotide polymorphisms ( SNPs) in HLA-C*06, CD84, IL12B, IL23R, TRAF3 IP2, ERAP1, IFIH1 and TNFAIP3. The decrease in Psoriasis Area and Severity Index ( PASI) was calculated as ∆ PASI (absolute PASI decrease compared with baseline) and PASI 75 (proportion of patients with ≥ 75% improvement vs. baseline). Associations between genetic variants and treatment outcome were assessed using multivariable linear regression analysis (∆ PASI corrected for baseline PASI, primary analysis) and Pearson's χ2-test or Fisher's exact test ( PASI 75, secondary analysis). Results We included 348 treatment episodes in 234 patients. Patients heterozygous ( GA) for the SNP in CD84 (rs6427528) had a better ∆ PASI response to etanercept after 3 months ( P = 0·025) than the homozygous reference group ( GG). In addition, patients heterozygous ( CT) for the IL12B variant showed a better response (∆ PASI) to ustekinumab ( P = 0·017) than the reference group ( CC). Patients homozygous ( GG) for the SNP in TNFAIP3 showed a worse response (∆ PASI) to ustekinumab ( P = 0·031) than the reference group ( TT). The associations with ustekinumab resulting from the primary analysis were not confirmed in the secondary ( PASI 75) analysis. Conclusions We demonstrated a strong association between etanercept use in psoriasis and variations in CD84, a gene that was previously found to be a predictor of response to etanercept in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

A letter to the editor on a research study on Autoinflammatory Disorders (AID) characterized by an unprovoked innate immune response, resulting in recurrent or ongoing systemic inflammation and fever, is presented.

Background Psychosocial stress can be a risk factor for the maintenance and exacerbation of chronic inflammatory diseases, such as psoriasis and rheumatoid arthritis ( RA). Objectives To gain insight into the specificity of the psychophysiological stress response during chronic inflammation, we assessed autonomic and neuroendocrine responses to stress in different chronic inflammatory diseases. Methods Thirty patients with psoriasis (nine women, mean age 58·5 years ± 12·4), 34 patients with RA (16 women, mean age 60·8 years ± 9·2) and 25 healthy controls (16 women, mean age 55·6 years ± 8·7) underwent a standardized psychosocial stress task ( Trier Social Stress Test). Salivary levels of α-amylase and cortisol and self-reported tension levels were measured before and after the stress test. Results The cortisol response to stress was heightened in patients with psoriasis compared with patients with RA and healthy controls, whereas there were no differences in the autonomic and self-reported measures. Conclusions The altered neuroendocrine stress response in patients with psoriasis suggests that stressful events might have different physiological consequences for specific patient groups with chronic inflammatory conditions, possibly adversely affecting disease status. [ABSTRACT FROM AUTHOR]

Tenascin-X is a large extracellular matrix glycoprotein that is widely distributed within connective tissues and is associated with an autosomal recessive type of Ehlers-Danlos syndrome (EDS). Tenascin-X represents the first EDS susceptibility gene that does not code for a fibrillar collagen or collagen-processing enzyme. We describe a paediatric case of tenascin-X deficiency and review the literature. [ABSTRACT FROM AUTHOR]

Application of sodium dodecyl sulphate (SDS) on the skin of healthy volunteers was used as a model for acute chemical injury. The time course of the response with respect to cell proliferation was studied using ornithine decarboxylase (ODC) activity. Erythema, polymorphonuclear leucocyte (PMN) infiltration, and the induction of epidermal antiproteinase activity (SKALP/elafin) were used as markers for the inflammatory response. ODC induction was similar to that in other models of acute skin injury, such as tape-stripping and ultraviolet light radiation. The amount of PMN infiltration correlated with erythema, but not with ODC induction. In contrast with findings in the tape-stripping model, no induction of SKAIP/elafin activity was found after SDS application. We conclude that cell proliferation as measured by ODC induction is a common feature in the various models for skin injury. Both the kinetics and the intensity of the inflammatory response, and the induction of epidermal antiproteinase activity, appear to vary, depending on the specific model. [ABSTRACT FROM AUTHOR]

Tenascin (hexabrachion, cytotactin) is an extracellular matrix glycoprotein whose expression Is strongly Increased in hyperproliferative skin diseases, as shown by immunohistochemistry with polyclonal sera. In this study we describe a new monoclonal antibody (T2H5) against human tenascin. The specificity of T2H5 was validated by sequential immunoprecipitation of tenascin with polyclonal sera. T2H5 was used to analyse the presence of tenascin in basal cell carcinoma. Using Western blotting, at least two forms of tenascin were found, with approximate molecular weights of 210 and 300 kDa. In cultured human skin fibroblasts only the high molecular weight form was found. [ABSTRACT FROM AUTHOR]

We report an investigation of peripheral blood polymorphonuclear leukocytes (PMN) from untreated patients with mild, quiescent psoriasis. Four aspects of the ‘metabolic burst’ were measured to illustrate phagocytosis-related events. These were: myeloperoxidase activity, hydrogen peroxide release, superoxide production and luminol-amplified chemiluminescence. Our study does not support the concept of an intrinsic abnormality of the PMN in psoriasis, but provides additional evidence for disease activity-dependent changes in phagocytic behaviour. Possible interactions with certain humoral factors, the so-called opsonins, are discussed. [ABSTRACT FROM AUTHOR]

Two new elastase inhibitors (SKALP, skin-derived antileucoproteases) were recently described in the lesional skin in psoriasis. The present study investigated the distribution of SKALP activity in the marginal zone of spreading psoriatic plaques. In a 4-mm zone immediately adjacent to the erythematosquamous plaques, SKALP activity was slightly increased compared to distant uninvolved skin. Within the lesion the anti-elastase activity was pronounced, but was significantly higher in the central zone of the plaque compared to the periphery. The appearance of SKALP in the psoriatic lesion appears to be a late event compared to endothelial involvement, intraepidermal accumulation of PMNs, epidermal proliferation and abnormal keratinization. This observation lends further support for the hypothesis that the induction of anti-elastase activity is associated with the off-switch of cutaneous inflammation. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response., Objectives: We aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohort., Methods: We investigated the copy number variation in the LCE3B and LCE3C genes, and eight single-nucleotide polymorphisms (SNPs) in HLA-C*06, CD84, IL12B, IL23R, TRAF3IP2, ERAP1, IFIH1 and TNFAIP3. The decrease in Psoriasis Area and Severity Index (PASI) was calculated as ∆PASI (absolute PASI decrease compared with baseline) and PASI 75 (proportion of patients with ≥ 75% improvement vs. baseline). Associations between genetic variants and treatment outcome were assessed using multivariable linear regression analysis (∆PASI corrected for baseline PASI, primary analysis) and Pearson's χ 2 -test or Fisher's exact test (PASI 75, secondary analysis)., Results: We included 348 treatment episodes in 234 patients. Patients heterozygous (GA) for the SNP in CD84 (rs6427528) had a better ∆PASI response to etanercept after 3 months (P = 0·025) than the homozygous reference group (GG). In addition, patients heterozygous (CT) for the IL12B variant showed a better response (∆PASI) to ustekinumab (P = 0·017) than the reference group (CC). Patients homozygous (GG) for the SNP in TNFAIP3 showed a worse response (∆PASI) to ustekinumab (P = 0·031) than the reference group (TT). The associations with ustekinumab resulting from the primary analysis were not confirmed in the secondary (PASI 75) analysis., Conclusions: We demonstrated a strong association between etanercept use in psoriasis and variations in CD84, a gene that was previously found to be a predictor of response to etanercept in rheumatoid arthritis., (© 2016 British Association of Dermatologists.)