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Background: Key pathogenic events of psoriasis and atopic eczema (AE) are misguided immune reactions of the skin. IL‐17C is an epithelial‐derived cytokine, whose impact on skin inflammation is unclear. Objective: We sought to characterize the role of IL‐17C in human ISD. Methods: IL‐17C gene and protein expression was assessed by immunohistochemistry and transcriptome analysis. Primary human keratinocytes were stimulated and expression of cytokines chemokines was determined by qRT‐PCR and luminex assay. Neutrophil migration towards supernatant of stimulated keratinocytes was assessed. IL‐17C was depleted using a new IL‐17C‐specific antibody (MOR106) in murine models of psoriasis (IL‐23 injection model) and AE (MC903 model) as well as in human skin biopsies of psoriasis and AE. Effects on cell influx (mouse models) and gene expression (human explant cultures) were determined. Results: Expression of IL‐17C mRNA and protein was elevated in various ISD. We demonstrate that IL‐17C potentiates the expression of innate cytokines, antimicrobial peptides (IL‐36G, S100A7 and HBD2) and chemokines (CXCL8, CXCL10, CCL5 and VEGF) and the autocrine induction of IL‐17C in keratinocytes. Cell‐free supernatant of keratinocytes stimulated with IL‐17C was strongly chemotactic for neutrophils, thus demonstrating a critical role for IL‐17C in immune cell recruitment. IL‐17C depletion significantly reduced cell numbers of T cells, neutrophils and eosinophils in murine models of psoriasis and AE and led to a significant downregulation of inflammatory mediators in human skin biopsies of psoriasis and AE ex vivo. Conclusion: IL‐17C amplifies epithelial inflammation in Th2 and Th17 dominated skin inflammation and represents a promising target for the treatment of ISD. [ABSTRACT FROM AUTHOR]

Summary: Background: Conventional analyses present aggregate data, masking late responders and efficacy reductions. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)‐17A, shows sustained efficacy in moderate‐to‐severe psoriasis. Objectives: To determine stability of response to secukinumab, changes in efficacy were assessed in individual patients. Methods: This is a post hoc analysis of two phase III randomized controlled trials, FIXTURE (trial registration: NCT01358578) and CLEAR (trial registration: NCT02074982). Patients received secukinumab 300 mg (FIXTURE and CLEAR), etanercept 50 mg (FIXTURE) or ustekinumab 45 or 90 mg (CLEAR) over 52 weeks. Mutually exclusive response categories were defined: ≥ 90% improvement in the Psoriasis Area and Severity Index (PASI 90) ('excellent'), ≥ 75% improvement in PASI (PASI 75) and < PASI 90 ('good') and < PASI 75 ('insufficient'). Reductions in efficacy were defined as shifts from higher to lower response categories between two consecutive visits maintained for a third consecutive visit. Loss of efficacy was defined as a reduction of efficacy resulting in 'insufficient' response. All comparisons are descriptive. Results: At 52 weeks, in CLEAR, 90·2% (303/336) of patients on secukinumab achieved stable efficacy without loss and 77·7% (261/336) showed stable efficacy without any reduction of response [74·3% (252/339) and 59·9% (203/339) of patients for ustekinumab]. In FIXTURE, 83·5% (273/327) and 66·4% (217/327) of patients on secukinumab had stable efficacy without loss or reduction of response [58·3% (190/326) and 42·6% (139/326) for etanercept]. Response was regained by continuing secukinumab treatment in 50% (8/16) of patients in CLEAR and 26% (9/34) in FIXTURE. Similar patterns were observed for other response definitions. Conclusions: Efficacy with secukinumab was stable over 52 weeks of treatment in most patients. Continued treatment with secukinumab resulted in regain of efficacy in some patients. Persistent loss of response was uncommon. What's already known about this topic? Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)‐17A, shows significant and sustained efficacy in the treatment of moderate‐to‐severe psoriasis.Secondary loss of response may be experienced by a minority of patients treated with secukinumab, as with other biologics, but the extent of this and the potential for regain of efficacy with continued treatment is not well understood. What does this study add? To determine stability of response to secukinumab and inform clinical practice, changes in efficacy were assessed at individual patient level using response categories.Efficacy with secukinumab was stable over 52 weeks of treatment in most patients, and continued treatment with secukinumab resulted in efficacy regain after loss in some patients. Persistent loss of response was uncommon.Patient factors such as body weight may affect the likelihood of loss of efficacy. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Background: Imbalances of T‐cell subsets are hallmarks of disease‐specific inflammation in psoriasis. However, the relevance of B cells for psoriasis remains poorly investigated. Objective: To analyse the role of B cells and immunoglobulins for the disease‐specific immunology of psoriasis. Methods: We characterized B‐cell subsets and immunoglobulin levels in untreated psoriasis patients (n = 37) and compared them to healthy controls (n = 20) as well as to psoriasis patients under disease‐controlling systemic treatment (n = 28). B‐cell subsets were analysed following the flow cytometric gating strategy based on the surface markers CD24, CD38 and CD138. Moreover, immunofluorescence stainings were used to detect IgA in psoriatic skin. Results: We found significantly increased levels of IgA in the serum of treatment‐naïve psoriasis patients correlating with disease score. However, IgA was only observed in dermal vessels of skin sections. Concerning B‐cell subsets, we only found a moderately positive correlation of CD138+ plasma cells with IgA levels and disease score in treatment‐naïve psoriasis patients. Confirming our hypothesis that psoriasis can develop in the absence of functional humoral immunity, we investigated a patient who suffered concomitantly from both psoriasis and a hereditary common variable immune defect (CVID) characterized by a lack of B cells and immunoglobulins. We detected variants in three of the 13 described genes of CVID and a so far undescribed variant in the ligand of the TNFRSF13B receptor leading to disturbed B‐cell maturation and antibody production. However, this patient showed typical psoriasis regarding clinical presentation, histology or T‐cell infiltrate. Finally, in a group of psoriasis patients under systemic treatment, neither did IgA levels drop nor did plasma cells correlate with IgA levels and disease score. Conclusion: B‐cell alterations might rather be an epiphenomenal finding in psoriasis with a clear dominance of T cells over shifts in B‐cell subsets. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Background: The main function of sebocytes is considered to be the production of lipids to moisturize the skin. However, it recently became apparent that sebocytes release chemokines and cytokines and respond to proinflammatory stimuli as well as the presence of bacteria. Objectives: To analyse the functional communication between human sebocytes and T cells. Methods: Immunofluorescence stainings for CD4 and interleukin (IL)‐17 were performed on acne sections and healthy skin. Migration assays and T‐cell‐stimulation cultures were performed with supernatants derived from unstimulated or prestimulated SZ95 sebocytes. Dendritic cells were generated in the presence of SZ95 supernatant and subsequently used in mixed leucocyte reactions. Results: We showed that CD4+ IL‐17+ T cells accumulate around the pilosebaceous unit and are in close contact with sebocytes in acne lesions. By using SZ95 sebocyte supernatant, we demonstrate a chemotactic effect of sebocytes on neutrophils, monocytes and T cells in a CXCL8‐dependent manner. Furthermore, sebocyte supernatant induces the differentiation of CD4+ CD45RA+ naive T cells into T helper (Th)17 cells via the secretion of IL‐6, transforming growth factor‐β and, most importantly, IL‐1β. No direct effects of sebocytes on the function of CD4+ CD45RO+ memory T cells were detected. Moreover, sebocytes functionally interact with Propionibacterium acnes in the maturation of dendritic cells, leading to antigen‐presenting cells that preferentially prime Th17 cells. Conclusions: Our study provides evidence that human sebocytes actively participate in inflammatory processes in the skin by recruiting and communicating with immune cells. This interaction leads to the generation of Th17 cells, which might contribute to the pathogenesis not only of acne vulgaris, but also of several inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

Background Psoriasis is a disease of enormous socio-economic impact. Despite approval of numerous highly efficient and costly therapies, a minor proportion of severely affected patients actually receives sufficient treatment. Objective To investigate whether addictions are associated with psoriasis and to develop evidence-based recommendations for dermatologists in their daily clinical practice in order to improve medical assessment of psoriasis and patients' quality of life. Patients and Methods Psoriasis patients at the University Department of Dermatology were asked to fill out a paper-based self-reported anonymous questionnaire with 92 questions of validated screening tests for the six most common addictions in Germany (alcohol, nicotine, drugs and illegal drugs, gambling, food). Body weight and height as well as current Psoriasis Area and Severity Index ( PASI) were documented as well. Results Between October 2015 and February 2016, 102 patients (65 males, 37 females; mean age 49.7 years ( SD 13.4), range 18-83 years) participated in the study. Fifty-seven of the 102 patients showed addictive behaviour. Of these, 23.8% were high-risk drinkers, 41% regular smokers, 11% at risk of drug abuse, 4.1% at risk of food dependency and 19% compulsive gamblers. Compared with the general population, these results are significantly higher for alcohol abuse ( P < 0.005), nicotine ( P < 0.001) and gambling ( P < 0.001). Body mass index was significantly higher in the study population ( P < 0.001). Conclusion Addictions and gambling are more prevalent in patients with psoriasis compared with the general population. Respective screening measures are recommended in daily practice for doctors treating psoriasis patients, and Peak PASI is suggested as a score to document patients' lifetime highest PASI. Parallel to new drug approvals and even more detailed insights into the pathomechanism of psoriasis, public health strategies and interdisciplinary approaches are essential for a general sustained psoriasis treatment. [ABSTRACT FROM AUTHOR]

The article focuses on a study characterizing alopecia areata ((A)-specific T-cell profiles and inflammatory pattern using a comparison of AA and coexisting inflammatory skin diseases. It states that an in-depth analysis was performed in 112 patients with AA and atopic eczema (AE), AA and psoriasis, all three, and AA and lichen planus using immunohistochemistry, histology, and cytokine staining of T cells. It reports a higher incidence of T-cell-driven inflammatory skin diseases in AA patients.

Th17 cells have been shown to play an important role in the pathogenesis of a variety of autoimmune diseases. The aim of this study was to investigate the potential role of Th17 cells in autoimmune pancreatitis (AIP). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine gene expression of the signature cytokines of Th17 cells IL-17A and IL-21 and of the Th17 lineage-specific transcription factor retinoic acid receptor-related orphan receptor C (RORC) in human tissue specimens of AIP, classical chronic pancreatitis (CP), and normal pancreas (NP). Infiltrating immune cells were characterized by immunohistochemistry (IHC). Gene expression of IL-17A, IL-21, and RORC were found to be significantly increased in AIP. Accordingly, the number of Th17 cells was significantly increased in AIP compared to NP or CP. Both gene expression analysis and IHC revealed a clear difference between type 1 and 2 AIP. In the periductal compartment of type 2 AIP, which is characterized by granulocytic epithelial lesions (GELs), the number of infiltrating Th17 cells and neutrophilic granulocytes was significantly increased compared to type 1 AIP. Our data suggest that Th17 cells play a role in the pathogenesis of AIP, in particular of type 2 AIP. Cross-talk between Th17 cells and neutrophilic granulocytes mediated via IL-17A may be a potential mechanism by which neutrophils are recruited to the duct and acinar cells with subsequent destruction, a process that is pathognomonic for type 2 AIP. [ABSTRACT FROM AUTHOR]

Summary: 银屑病影响全球至少 1 亿人, 该疾病导致皮肤出现红色鳞状斑块, 病灶可能会覆盖很大身体面积,也可能影响指甲、头皮、手掌和脚底。这可能导致生活质量严重受损。 对于中度至重度疾病患者, 使用称为生物疗法的药物可能会使皮肤完全康复或几乎完全康复。由于银屑病是一种长期疾病, 因此生物疗法的长期疗效对患者很重要。但有些患者最终可能停止对生物治疗的应答, 这意味着药物不再有效。 患者在多大程度上停止应答, 以及继续治疗时后续恢复应答的比率(意味着治疗再次开始有效)是多少, 尚未在个体患者层面进行这些研究。关于药物治疗疾病(其疗效)的持续能力的研究称为药物稳定性研究。 苏金单抗是银屑病的一种许可的生物疗法,其在大型临床试验中显示具有持久的疗效和安全性。在 16 周的治疗期内,苏金单抗治疗可使银屑病减少 90%,而且研究证明长期疗效长达 5 年。 在本研究中,德国和美国的研究人员研究了苏金单抗在参加两项大型临床试验的人群中的应答稳定性。他们发现,在大多数患者中, 苏金单抗的疗效在一年治疗期内保持稳定, 而且苏金单抗继续治疗可使某些患者恢复失去的疗效。持续应答丧失不常见。 患者因素(包括体重、既往生物治疗失败及血浆中的药物水平)可能影响应答的稳定性。 This summary relates to the study: 苏金单抗继续治疗与应答高保留或恢复率有关 Linked Article: Augustin et al. Br J Dermatol 2020; 182:67–75 [ABSTRACT FROM AUTHOR]

Summary: Affecting at least 100 million people worldwide, psoriasis is a disease causing red, scaly patches of skin that may cover a large area of the body and may also affect the nails, scalp, palms and soles. This can lead to a severe impairment in quality of life. For patients with moderate to severe disease, the use of drugs called biologic therapies can result in clear or almost clear skin. Since psoriasis is a long‐term condition, it is important for patients to experience long‐lasting effects from biologic therapies. However, some patients can eventually stop responding to biologic treatments, meaning the drugs no longer work. The extent to which patients stop responding, and rates of subsequent regain of response with continued treatment (meaning it starts working again), have not been studied at the level of individual patients. A study of a drug's continued ability to treat the disease (its efficacy) is known as a study of its stability. Secukinumab, a licensed biologic therapy for psoriasis, has shown long lasting efficacy and safety in large clinical trials. Treatment with secukinumab can achieve a 90% reduction of psoriasis within 16 weeks of treatment and long term efficacy has been demonstrated up to 5 years. In this study, investigators from Germany and the U.S.A. studied the stability of response to secukinumab in people who took part in two large clinical trials. They found that efficacy with secukinumab was stable over one year of treatment in most patients, and continued treatment with secukinumab resulted in a regain of efficacy after loss in some patients. Persistent loss of response was uncommon. Patient factors including body weight, previous biologic treatment failure and levels of the drug in the blood plasma could influence the stability of response. This summary relates to the study: Continued treatment with secukinumab is associated with high retention or regain of response Linked Article: Augustin et al. Br J Dermatol 2020; 182:67–75 [ABSTRACT FROM AUTHOR]

B Is the humoral immunity dispensable for the pathogenesis of psoriasis? This corrigendum is to note that the name of Prof. Carsten Schmidt-Weber was inadvertently omitted as an author in the initial version of the paper. [Extracted from the article]

Copyright of British Journal of Dermatology is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: The main function of cells in the skin called sebocytes is considered to be the production of lipids (oils) to moisturize the skin. It used to be thought that they were bystander cells during skin inflammation with no impact on the body's immune response, meaning they did not help the body to fight off signs of infection on inflammation. However, it recently became apparent that sebocytes do in fact respond to signs of inflammation (proinflammatory stimuli) as well as the presence of bacteria, and they release tiny protein molecules called chemokines and cytokines which play a role in inflammation. This discovery prompted scientists from Germany and Hungary to examine samples of skin with acne and skin without acne, to see if sebocytes also have any influence over white blood cells of the immune system (immune cells). The researchers found that sebocytes do indeed participate in inflammatory processes in the skin by recruiting and communicating with immune cells, and this interaction leads to the generation of Th17 cells. Further studies have to clarify whether this relationship between sebocytes and Th17 cells helps the immune system or, on the contrary, contributes to the development not only of acne, but also of several inflammatory skin diseases. [ABSTRACT FROM AUTHOR]