Fine mapping of the PSORS4 psoriasis susceptibility region on chromosome 1q21

Psoriasis is a chronic skin disorder affecting approximately 2% of the Caucasian population. Family clustering of the disease is well established and nonparametric linkage analyzes have mapped disease susceptibility loci on chromosomes 6p (PSORS1) and 17q (PSORS2). Nonconfirmed evidence for linkage is also available for chromosomes 2q 3q, 4q (PSORS3), 8q, 16q, and 20p. We mapped an additional susceptibility locus on chromosome 1q21 (PSORS4). In this study, we have carried out a linkage disequilibrium analysis, in order to achieve a finer localization. We recruited 79 triads from continental Italy and typed them at five loci spanning the 1.6 Mb region generating the highest multipoint LOD scores in our previous linkage study. We observed significant evidence for association with D1S2346 marker (p = 0.004). Results consistent with this data were obtained by typing an independent sample that included 28 patients and 56 controls, originating from Sardinia. In fact, p values of 0.02 were observed with both D1S2346 and D1S2715 markers. We sought further confirmation of our results by typing both samples with two novel markers (140J1C and 140J1D) flanking D1S2346. Marker 140J1D generated a p value of 0.003 in the continental Italy sample where a D1S2346/140J1D haplotype was found with a higher frequency among patients' chromosomes. Altogether our data indicate that the 1q21 susceptibility gene may be localized in the genomic interval spanned by D1S2346 and 140J1D. This report provides evidence supporting the refinement of a non-HLA psoriasis susceptibility locus.     

Investigation of adrenomedullary function in atopic dermatitis

Adrenomedullary function in patients with atopic dermatitis was assessed by measurement of plasma levels of catecholamines (adrenalin and noradrenalin) and cyclic AMP in response to the stimuli of standing after lying supine, and a 5-min infusion of histamine in the standing position (i.e. histamine plus standing). Plasma clearance of adrenalin was examined by measurement of plasma catecholamine and cyclic AMP levels following a 15-min intravenous infusion of adrenalin in the supine position. Resting plasma levels of adrenalin, cyclic AMP and noradrenalin were not statistically different in atopic patients and normal controls. Standing or intravenous infusion of histamine in the standing position caused a rise in plasma catecholamine levels. Plasma adrenalin, cyclic AMP and noradrenalin levels in response to these stimuli and the rate of clearance of exogenous adrenalin from the plasma were not significantly different in patients with atopic dermatitis and in normal subjects.     

Association and linkage of atopic dermatitis with chromosome 13q12-14 and 5q31-33 markers

Atopic dermatitis is a chronic inflammatory skin disease that affects 10-20% of the population. Linkage of atopy, asthma, allergic rhinitis, and total serum IgE levels to several different chromosomal regions have been described extensively, but little is known about the genetic control of atopic dermatitis. We tested for the association and linkage between atopic dermatitis and five chromosomal regions: 5q31-33, 6p21.3, 12q15-24.1, 13q12-31, and 14q11.2/14q32.1-32.3. Marker analysis was performed in two Caucasian populations: (i) 192 unrelated German children with atopic dermatitis and 59 non-atopic children from a German birth cohort study (MAS'90), parental DNA was tested in 77 of 192 children with atopic dermatitis; (ii) 40 Swedish families with at least one family member with atopic dermatitis selected from the International Study of Asthma and Allergy in Children. Evidence for linkage and allelic association for atopic dermatitis was observed for markers on chromosome 13q12-14 and 5q31-33.     

特应性皮炎基因位点及基因治疗进展

特应性皮炎是一种与遗传过敏素质有关的皮肤炎症性疾病。近几年，各国研究人员对特应性皮炎基因位点及基因治疗方面做了大量的研究。研究证明特应性皮炎的发病与SPINK5基因、PHFI1基因、表皮分化基因等密切相关。并运用离子透入法渗入白介素10反义寡核苷酸、用含有核因子-κB的寡聚脱氧核苷酸软膏、UVA1光线疗法等治疗特应性皮炎。     

特应性皮炎外周血白介素17水平检测

目的: 检测特应性皮炎(AD)患者血中白介素17(IL-17)水平.方法: 采用双抗体夹心ELISA法检测66例特应性皮炎患者和50名正常对照者血中IL-17含量.结果: 患者组血中IL-17水平明显高于对照组(P<0.001).重度组高于中度组(P<0.001),中度组与轻度组无统计学差异.结论: IL-17可能在AD患者的免疫发病机制中发挥作用.     

Possible pathogenic role of Th17 cells for atopic dermatitis

The critical role of IL-17 has recently been reported in a variety of conditions. Since IL-17 deeply participates in the pathogenesis of psoriasis and keratinocyte production of certain cytokines, the involvement of T helper cell 17 (Th17) in atopic dermatitis (AD) is an issue to be elucidated. To evaluate the participation of Th17 cells in AD, we successfully detected circulating lymphocytes intracellularly positive for IL-17 by flow cytometry, and the IL-17+ cell population was found exclusively in CD3+CD4+ T cells. The percentage of Th17 cells was increased in peripheral blood of AD patients and associated with severity of AD. There was a significant correlation between the percentages of IL-17+ and IFN-gamma+ cells, although percentage of Th17 cells was not closely related to Th1/Th2 balance. Immunohistochemically, IL-17+ cells infiltrated in the papillary dermis of atopic eczema more markedly in the acute than chronic lesions. Finally, IL-17 stimulated keratinocytes to produce GM-CSF, TNF-alpha, IL-8, CXCL10, and VEGF. A marked synergistic effect between IL-17 and IL-22 was observed on IL-8 production. The number of Th17 cells is increased in the peripheral blood and acute lesional skin of AD. Th17 cells may exaggerate atopic eczema.     

特应性皮炎与2型炎症反应

【摘要】 研究显示,2型炎症及其相关细胞因子白细胞介素4、13等在特应性皮炎（AD）中起关键作用。Th2细胞及2型细胞因子是2型炎症反应的核心驱动因素,主要通过3条路径参与AD发病：加重皮肤屏障缺陷;激活和强化瘙痒反应;调节性T细胞（Treg）病理性重编程为Th2样Treg细胞,从而放大2型炎症反应。本综述探讨2型炎症与AD的关系,希望有助于优化治疗方案,为AD患者提供新的治疗选择。     

特应性皮炎的转录组学研究进展

【摘要】 随着基因芯片技术、RNA测序技术等转录组学技术发展,特应性皮炎（AD）发病中重要的相关影响因素逐渐被揭示,如不同T辅助（Th）细胞的亚型以及其他免疫相关细胞如巨噬细胞、朗格汉斯细胞;在AD的瘙痒及皮肤屏障破坏方面,相关免疫细胞如Th2细胞及角质形成细胞等所释放白细胞介素4、白细胞介素13、聚丝蛋白、兜甲蛋白等活性物质的异常变化起着主要作用。同时,转录组技术已被用于分析患者治疗前后转录谱的变化从而对患者的病情和治疗效果进行评估等。本文总结近年来在AD转录组学方面的研究进展。     

Cromones in atopic dermatitis

Summary Three new cromones have been studied that are supposed to be better absorbed and to have a wider spectrum of anti-allergic activity than disodium cromoglycate. Pretreatment with i.d. injection of 10 g FPL 52758 significantly reduced the weal and flare reaction induced by specific antigen in 11 patients with atopic dermatitis. The weal and flare reaction was not reduced in the same patients when 1.5 mg of FPL 52758 was applied topically under occulusion for a 24-h period prior to challenge with antigen. The itch and slight pain caused by antigen injection was not experienced in the FPL 52758 pretreated areas.Preliminary clinical results were obtained with the cromone FPL 52757, but due to possible hepatotoxicity this trial was not completed. Another similar cromone without hepatotoxicity was used in a double blind within-patient study. Nine patients with mild to moderate atopic dermatitis were treated with FPL 57787 (5%) ointment and matching placebo ointment. No significant improvement was observed after 4 weeks of treatment with the cromone containing ointment.     

Lysozyme in atopic dermatitis

The aim of the present study was to determine the levels of lysozyme in serum and saliva in 10 patients with atopic dermatitis (AD). A significantly decreased lysozyme levels in saliva compared to controls (p less than 0.01) were showed, whereas no differences were found in lysozyme activity in serum of patients and controls. The reduced levels in saliva can hardly be explained. The decreased levels of lysozyme in external fluids may be one explanation for the well-known predisposition for AD patients to an increased susceptibility to many cutaneous infections.     

Pyridoxine in atopic dermatitis

Summary A previous study has reported benefit when pyridoxine hydrochloride was given to patients with atopic dermatitis. To investigate this in children, we performed a randomized, double-blind, parallel-group, placebo-controlled trial. Forty-eight children with moderate or severe atopic dermatitis were recruited and, of those who completed the study, 19 received pyridoxine hydrochloride 50 mg once daily for 4 weeks and 22 received placebo. Disease activity was monitored by clinical severity scores measuring the extent and degrees of erythema recorded by the investigator and symptom scores (daytime itch and nocturnal sleep disturbance) recorded by parents. There was no statistically significant difference between the two groups at the end of treatment. We have been unable to demonstrate clinical benefit from pyridoxine supplementation in children with atopic dermatitis.     

Urticaria in atopic dermatitis

During examinations of 479 patients referred for atopic dermatitis and 520 with urticaria it was found that in the first group coexistence of these diseases was frequently occurring, and in the second group it was rare. Food allergens caused slightly more frequently episodes of urticaria than exacerbations of atopic dermatitis. Coexistence of urticaria with atopic dermatitis was particularly frequent in patients: a) with a high IgE titre, b) with a history of allergy in the families of both parents, c) in patients with respiratory allergy associated with skin lesions.     

Biologics in atopic dermatitis

Atopic dermatitis (AD) accounts for a significant share of chronic inflammatory skin disorders. There is a niche for the development of biologics to treat recalcitrant autoinflammatory stage AD seen mostly in adults. The heterogeneity of patient response to various existing biotherapies points to involvement of various immune responses and suggests that therapies must preferably target early development of allergen‐specific B‐ and T‐cell clones. In addition to immune targets, tissue factors that help restore the normal epidermal environment constitute interesting therapeutic tools. Several approaches are needed to find the appropriate targets in a field where so many have been investigated without definitive proof of concept for human systemic therapy. The keys to success are probably (1) to influence the inflammatory skin pattern towards less pruritogenic effects, requiring us to better understand pruritogenic inflammation and (2) to limit the amplification loop of disease by attacking abnormal regulatory mechanisms which perpetuate skin autoinflammation.