The expression of mCTLA-4 in skin lesion inversely correlates with the severity of psoriasis

Background

Psoriasis is a chronic inflammatory disease characterized by epidermal hyperplasia and increased T cell infiltration. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a key factor that affects T cell function and immune response. However, whether the expression of CTLA-4 affects the severity of psoriasis is still unknown.

The psoriasis area and severity index is the adequate criterion to define severity in chronic plaque-type psoriasis

BACKGROUND: Chronic plaque-type psoriasis is a major dermatosis, but a significant question is still unanswered: What defines severity in chronic plaque-type psoriasis? While objective assessments like the Psoriasis Area and Severity Index (PASI) have frequently been used in clinical trials, quality of life (QOL) questionnaires are currently becoming more and more popular. OBJECTIVE: This article summarizes the most important objective and subjective measurements of severity in psoriasis. For every dermatologist it is critically important to distinguish between severe psoriasis and psoriasis that severely affects QOL. Even if the PASI also has disadvantages, it is the most adequate instrument available to evaluate severity in plaque-type psoriasis. RESULT: We provide reasons why PASI >12 defines severe, PASI 7-12 moderate and PASI <7 mild chronic plaque-type psoriasis.     

The serotonin transporter protein is expressed in psoriasis,where it may play a role in regulating apoptosis

Since the symptoms of psoriasis may be changed by treatment with selective serotonin reuptake inhibitors (SSRIs), the expression of serotonin (5-HT) and its transporter protein (SERT) in the skin of patients with psoriasis were examined employing a biotinylated-streptavidine procedure. In biopsies of such skin staining for 5-HT was limited to platelets; the expression of SERT in the keratinocytes of involved regions was redistributed; the numbers of SERT-positive dendritic or round mononuclear cells in the epidermis of involved psoriatic skin were higher than in normal healthy control skin; and the dermis of the involved skin contained higher numbers of round inflammatory cells immunostained for SERT than either non-involved psoriatic skin or normal skin. Double-immunostaining indicated that the skin cells expressing SERT also expressed CD1a, CD3 or tryptase. In addition, SERT immunostaining was co localized with caspase-3, a key regulator of apoptosis, but not with TUNEL staining. The present findings indicate that SERT might play a role in regulating apoptosis in inflammatory cells associated with psoriasis, in which case this protein might constitute a valuable therapeutic target.     

The relationship between oxidative stress,smoking and the clinical severity of psoriasis

Background Recent studies suggested that increased oxidant products and decreased antioxidant system functions may be involved in the pathogenesis of psoriasis. In this study, we investigated total oxidative status, Paraoxonase (PON)1/arylesterase enzyme activities and severity of the disease in smoker and non‐smoker psoriatic patients. Methods Fifty‐four patients with plaque type psoriasis (28 smokers and 26 non‐smokers) and 62 healthy volunteers (16 smokers and 46 non‐smokers) were enrolled in the study. Serum total oxidant status (TOS), total antioxidant capacity (TAC) and arylesterase levels were measured, and oxidative stress index (OSI) was calculated in all participants. Results Psoriasis Area and Severity Index scores were significantly higher in smoker patients than in non‐smoker patients (P = 0.014). Both smoker and non‐smoker patients had significantly increased TOS levels and OSI values and decreased TAC levels than healthy subjects (all P values = 0.000). The TAC and TOS levels, OSI values and arylesterase activities were similar between smoker and non‐smoker patients. The levels of triglyceride (TG), total cholesterol (TC), low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) were not significantly different between smoker and non‐smoker psoriasis patients. When compared with non‐smoking controls, only smoking psoriasis patients had significantly higher TG (P = 0.005), lower HDL (P = 0.022) and lower arylesterase levels (P = 0.015). There were no significant correlations with Psoriasis Area and Severity Index (PASI) scores and TAC, TOS, OSI, TG, TC, HDL and LDL levels in all psoriasis patients. Conclusions Oxidative stress is increased in psoriasis patients regardless of their smoking status. The decreased arylesterase activity in smoker psoriasis patients suggested that smoking may be a considerable risk factor that increases the severity of psoriasis by increasing oxidative stress in these patients.     

Analysis of a functional serotonin transporter promoter polymorphism in psoriasis vulgaris

Serotonin is a monoamine acting as a neuromediator in the central and peripheral nervous system. Recently, serotonin has also been shown to influence T- and B-cell function. The serotonin transporter is central in the regulation of the serotonergic system and widely expressed on cells of the immune system. A functional length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) has been implicated in the genetic background of depression. Psoriasis is a complex disease with a polygenetic inheritance. In light of the role of T-cell mediated inflammation in psoriasis and the increased prevalence of depression in psoriatic patients, we analyzed the 5-HTTLPR polymorphism in 309 patients with psoriasis vulgaris and 315 healthy control individuals. No significant differences in genotype distribution and allele frequencies were found. There was also no difference in the score of the Hamilton Rating Scale for Depression in patients with psoriasis (n = 137) characterized by carriage of different 5-HTTLPR genotypes. These findings argue against a major contribution of the 5-HTTLPR polymorphism to psoriasis susceptibility and the occurrence of depressive symptoms among psoriatic patients.     

Serum methylglyoxal level and its association with oxidative stress and disease severity in patients with psoriasis

Psoriasis vulgaris (PV), a chronic inflammatory skin disease, is a condition of increased oxidative stress (OxS). However, interest related to oxidative and carbonyl stress damages to proteins, such as the formation of advanced glycation end products (AGEs) and their precursor molecule methylglyoxal (MG) has been modest. The objective of this study was to compare the systemic levels of OxS markers in patients with PV and healthy controls (Co) and to investigate their correlation with the serum level of MG. Total peroxide concentration (TPX) and total antioxidant capacity (TAC) were estimated by means of spectrophotometry. The TPX and TAC ratio was regarded as OxS index (OSI). MG level was determined using ELISA. Compared to Co, patients with PV had significantly increased blood levels of TPX (P < 0.0001), OSI (P < 0.0001), and MG (P = 0.01), and lower TAC levels (P < 0.0001). Increase in body mass index (BMI) appeared to contribute to this imbalance as TAC levels decreased with increasing BMI (r = ?0.252, P < 0.01). Increased TPX concentration was associated with higher serum level of MG (r = 0.610, P = 0.004), the latter being positively correlated with psoriasis area and severity index (r = 0.577, P = 0.008). In performed multivariate regression analysis, TPX, TAC, and OSI were all significant predictors of MG level. Our study gave further proof of increased systemic psoriasis-related OxS. MG serum level, reflecting simultaneously OxS as well as carbonyl stress status, could be used as a marker of disease activity in clinical trials while looking for new systemic therapies for psoriasis.     

Relationship between smoking‐induced oxidative stress and the clinical severity of psoriasis

Background Psoriasis is a chronic and recurrent inflammatory skin disease, known as an oxidative stress condition. Smoking augments the risk of development of psoriasis. Although the relative importance of potential mechanisms of smoking‐induced psoriasis is unknown, direct delivery of oxidants has been implicated in the pathogenesis of smoking‐induced psoriasis. Objectives This study aimed to investigate the smoking‐induced oxidative stress in psoriatic patients and its correlation with the severity of the disease. Methods The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in 25 psoriatic patients (10 smokers, 10 non‐smokers and 5 ex‐smokers) and 20 healthy control subjects (10 smokers and 10 non‐smokers). Clinical severity of psoriasis was determined according to the Psoriasis Area Severity Index (PASI) score. Results Our results showed a significant increase in serum MDA and decrease in the blood SOD levels in psoriatic patients compared with those in control subjects and those in smokers compared with those in non‐smokers. The concentrations of MDA and SOD were significantly correlated with PASI score. There was a significant increase in PASI score in smoker patients compared with that in non‐smokers and it increased with increasing the pack‐years of smoking. Conclusions Our results indicate that smoking‐induced oxidative damage resulting from increased reactive oxygen species production along with insufficient capacity of antioxidant mechanisms may be involved in the pathogenesis of psoriasis.     

寻常性银屑病患者血清白细胞介素-26水平与疾病严重度相关性分析

目的:检测寻常性银屑病患者血清中白细胞介素(IL)-26的表达量,并分析其对疾病严重程度的影响.方法:选取2017年12月-2019年1月来山西医科大学第一附属医院就诊的寻常性银屑病患者84例作为观察组,其中进展期患者40例,静止期患者44例;选择同期在该院进行健康体检的志愿者40例作为对照组.采用流式细胞术检测2组患...     

Demographic and clinical correlates of extent of psoriasis during stable disease and during flares in chronic plaque psoriasis

BACKGROUND: Following a previous population-based study, we define a common psoriatic phenotype (A) with a limited area of involvement of stable disease but extensive flares and a less common phenotype (B) with consistently widespread disease. OBJECTIVES: To define these phenotypes quantitatively and to investigate any biological significance through correlations with clinical disease characteristics. Psoriatic plaque thickness was also included in the analyses. METHODS: Two hundred and ninety-four patients who had had chronic plaque psoriasis for at least 5 years were recruited. Area of involvement during stable disease (A(basal)) and during the most severe flare (A(max)) were derived from current area of involvement and patient history. Mean plaque thickness (T) was calculated from a current Psoriasis Area and Severity Index score. RESULTS: Multivariate regression of each variable on A(basal), A(max) and T showed many highly significant relationships. Usually A(basal) and A(max) were retained in the final models but with some variables only A(basal) was retained, suggesting an intrinsic effect unrelated to A(max). Phenotype A was associated with female gender, age at onset < 40 years, exacerbation by sore throat and stress, decreased concern about psoriasis and good response to ultraviolet B and methotrexate. A(basal) was individually associated with nail and joint involvement and need for second-line therapy. T was related to male gender, nail involvement and decreased exacerbation by stress on univariate analysis but only to nail disease on multivariate analysis. CONCLUSIONS: The phenotypes have been shown to have biological significance. A(basal) and A(max) may be useful therapeutic indices of long-term severity in clinical trials and in the investigation of genetic/environmental influences on psoriasis severity.     

Sharpin蛋白在寻常型银屑病皮损内的表达及其与PASI评分关系的研究

目的:探讨Sharpin蛋白在寻常型银屑病皮损内的表达及其与PASI评分的关系。方法:采用实时荧光定量PCR及免疫组织化学方法检测Sharpin在寻常型银屑病及正常皮肤内的表达,并探讨其与临床病理特征的关系。结果:Sharpin mRNA在寻常型银屑病皮损内较正常皮肤内表达明显升高,两者差异有统计学意义(t=0.03,P0.05);免疫组化结果提示Sharpin蛋白在寻常型银屑病皮损内高表达,且在寻常型银屑病皮损内的阳性表达率高于正常皮肤组织,平均染色得分亦高于正常皮肤(P值均0.05)。此外,Sharpin蛋白表达与治疗前寻常型银屑病PASI评分呈正相关(r=0.83,P0.05)。结论:Sharpin蛋白可能参与了银屑病发病机制,对提示银屑病病情及预后可能具有一定的意义。     

Epidermal innervation correlates with severity of photodamage

Abstract Intraepidermal nerve fibers were studied by electron microscopy in chronically photodamaged preauricular skin and in paired sun-protected postauricular sites of 20 Caucasian women aged 56–70 years. As previously reported, basal keratinocytes in the sun-exposed skin showed various degrees of degenerative changes including intracellular vacuolar structures and widened intercellular spaces. Neurites were frequently closely apposed to basal keratinocytes in preauricular sun-exposed skin, but were observed less than 10% as often in sun-protected postauricular skin. When degree of epidermal photodamage was quantified by means of the number of degenerated keratinocytes per 100 keratinocytes in the basal layer, the number of intraepidermal nerve libers was significantly correlated by linear regression analysis to the severity of epidermal photodamage (r=0.913) independent of anatomical sites. These results demonstrate for the first time a correlation between degree of epidermal innervation and chronic photodamage and suggest the possibility of neural involvement in the pathophysiology and/or repair of photodamaged skin.     

Maxemeter(R)和Corneofix(R)对寻常性银屑病病情的评判

目的:探讨采用皮肤黑素和血红素测量仪Maxemeter和Corneofix粘贴片法评判银屑病红斑程度和表皮角质形成细胞变化上的应用前景.方法:选取52例寻常性银屑病患者,采用Maxemeter M16 测定红斑指数和Corneofix粘贴片检测表皮代谢情况.结果:红斑指数进行期为625.83,稳定期为624.80,消退期为608.22,进行期与消退期、稳定期与消退期的差异有统计学意义;表皮样本角化不全细胞计数进行期与稳定期,稳定期与消退期,进行期与消退期的差异均有统计学意义.并与银屑病皮损面积和严重程度指数(PASI)评分存在一定的相关性.结论:Maxemeter和Corneofix是两种简便易行的检测方法,可以作为银屑病病情判断的客观手段.