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Background: Bullous pemphigoid (BP) is a rare, autoimmune, blistering skin disease associated with high disease burden, profoundly decreased quality of life and increased morbidity. Emerging evidence supports an important role for type 2 inflammation in disease pathogenesis. Current management relies on topical and/or systemic corticosteroids, non-selective immunosuppressants and antibiotics with anti-inflammatory properties, which are all limited by side effects and toxicities. Therefore, targeted, efficacious and safe therapies are needed. Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation. Several reports of patients successfully treated with dupilumab have been published; however, dupilumab has not been formally assessed in a double-blind, placebo-controlled trial. Objectives: We report the design of LIBERTY-BP ADEPT, a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of dupilumab in adults with BP. Methods: LIBERTY-BP ADEPT comprises a 35-day screening, 52-week treatment and 12-week follow-up period. Approximately 98 adults aged 18–90 years with moderate-to-severe BP are being enrolled at 51 sites on 4 continents and randomized 1:1 to subcutaneous dupilumab or placebo every 2 weeks. All participants will receive concomitant oral corticosteroids (OCS). Planned Outcomes: The primary endpoint is the proportion of patients achieving complete remission off steroid therapy at week 36. Key secondary endpoints include total cumulative OCS dose to week 36, percent change and proportion of patients with ≥ 4-point reduction in the weekly average of daily Peak Pruritus Numerical Rating Scale from baseline to week 36 and percent change in Bullous Pemphigoid Area Index score from baseline to week 36. Conclusion: The trial results will provide evidence on whether the efficacy and safety of dupilumab support its use as a potential novel treatment approach for BP and will provide new insights into the role of type 2 inflammation in BP pathogenesis. Clinical Trial Registration: ClinicalTrials.gov identifier NCT04206553. [ABSTRACT FROM AUTHOR]

Background: Two phase III trials, ECZTRA 1 and 2, confirmed the efficacy and safety of tralokinumab versus placebo in adults with moderate-to-severe atopic dermatitis (AD). To further explore the long-term efficacy of tralokinumab for AD, a pooled analysis of these trials was conducted. Methods: ECZTRA 1 and 2 patients (n = 1596 total) were randomized to tralokinumab 300 mg or placebo every 2 weeks (q2w) over 16 weeks. Patients achieving Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) and/or 75% improvement in the Eczema Area and Severity Index (EASI-75) at Week 16, were re-randomized to tralokinumab q2w, every 4 weeks (q4w), or placebo (tralokinumab withdrawal) for another 36 weeks. Patients not achieving the response criteria at Week 16 received open-label tralokinumab q2w plus optional topical corticosteroids (TCS). A pooled, prespecified analysis assessed the proportions of Week 16 responders that maintained IGA 0/1 and/or EASI-75 at Week 52. Pooled data from all patients initiated with tralokinumab, regardless of the response at Week 16 or dosing regimen received thereafter, were analyzed post hoc. Results: In patients who achieved the primary endpoints at Week 16, IGA 0/1 responses were maintained at Week 52 without rescue treatment (including TCS) by 55.9%, 42.4%, and 34.0% of patients re-randomized to tralokinumab q2w, q4w, or placebo (tralokinumab withdrawal), respectively, while EASI-75 responses were maintained by 57.3%, 50.4%, and 26.4%, respectively (prespecified analysis). In a post hoc analysis of all patients initiated with tralokinumab, response rates improved over time with continued tralokinumab treatment beyond Week 16 to Week 52 for EASI-50 (63.1–82.7%), EASI-75 (37.6–61.8%), EASI-90 (20.4–37.3%), and IGA 0/1 (23.0–36.2%). Conclusions: Tralokinumab treatment provides progressive and sustained improvement over 1 year in the extent and severity of AD in patients with moderate-to-severe AD. Clinical Trial Registration: NCT03131648 (ECZTRA 1); study start date: 30 May 2017; primary completion date: 7 August 2018; study completion date: 10 October 2019. NCT03160885 (ECZTRA 2); study start date: 12 June 2017; primary completion date: 4 September 2019; study completion date: 14 August 2019. Infographic: Plain Language Summary: Atopic dermatitis (AD) is a chronic inflammatory disease characterized by excessively dry and itchy skin, resulting in a considerable burden of disease. Patients with AD often require long-term treatment. Tralokinumab is an injectable antibody treatment that targets a protein called interleukin-13, which substantially contributes to the signs and symptoms of AD. In the ECZTRA 1 and 2 phase III clinical trials, funded by LEO Pharma A/S, adults with moderate-to-severe AD treated with tralokinumab every other week for 16 weeks showed significant improvement in disease extent and severity compared with patients receiving placebo. To further explore the long-term efficacy of tralokinumab for AD, we performed a new analysis combining the almost 1600 patients of ECZTRA 1 and 2. A large proportion of patients treated with tralokinumab who achieved clear or almost clear skin at Week 16 were able to maintain clear or almost clear skin at Week 52 with less frequent dosing (every 4 weeks). Additionally, combining all patients treated with tralokinumab, regardless of Week 16 response or dose frequency thereafter, showed that most patients achieved a significant reduction in disease extent and severity at Week 52. These results demonstrate that many tralokinumab-treated patients continue to improve beyond Week 16, and highlight that efficacy results at Week 16 may not be representative of the outcome of longer-term tralokinumab treatment. These findings may help health care providers better advise patients regarding when to modify treatment with tralokinumab. [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.)

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.)

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.)

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 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.)

uscular mycorrhizal (AM) fungi influence the expression of defence-related genes in roots and can cause systemic resistance in plants probably due to the induced expression of specific defence proteins. Among the different groups of defence proteins, plant food allergens were identified. We hypothesized that tomato-allergic patients differently react to tomatoes derived from plants inoculated or not by mycorrhizal fungi. To test this, two tomato genotypes, wild-type 76R and a nearly isogenic mycorrhizal mutant RMC, were inoculated with the AM fungus Glomus mosseae or not under conditions similar to horticultural practice. Under such conditions, the AM fungus showed only a very low colonisation rate, but still was able to increase shoot growth of the wild-type 76R. Nearly no colonisation was observed in the mutant RMC, and shoot development was also not affected. Root fresh weights were diminished in AM-inoculated plants of both genotypes compared to the corresponding controls. No mycorrhizal effects were observed on the biomass and the concentration of phosphate and nitrogen in fruits. Real-time quantitative polymerase chain reaction analysis revealed that six among eight genes encoding for putative allergens showed a significant induced RNA accumulation in fruits of AM-colonised plants. However, human skin reactivity tests using mixed samples of tomato fruits from the AM-inoculated and control plants showed no differences. Our data indicate that AM colonisation under conditions close to horticultural practice can induce the expression of allergen-encoding genes in fruits, but this does not lead necessarily to a higher allergenic potential. [ABSTRACT FROM AUTHOR]

Cellular inflammation of the nasal mucosa demonstrates a local immune response which plays an important role in allergic rhinitis. The aim of the present study was to characterize nasal mucosal lymphocytes regarding their activation and differentiation state by direct ex vivo flowcytometric analysis. Lymphocytes from the inferior turbinates were isolated by a mechanical method of preparation and, for comparison, from peripheral blood by Ficoll gradient centrifugation. Patients suffering from rhinitis or difficulty in nasal breathing were divided into an allergic (pollen-allergy, n = 13) and non-allergic group ( n = 24). Expression of different T- and B-cell markers was determined by flowcytometric analysis. CD4+ T-cells from the nasal mucosa exhibited a memory phenotype (CD45RO+, 97%), were highly activated (CD69+, 43–73%), and showed low expression of the cutaneous lymphocyte antigen (CLA+, 5%). Nasal CD20+ B-lymphocytes expressed significantly higher levels of mIgE and lower levels of CD23 and CD80 than peripheral B-cells. Subsets of CD80+ (4%) and CD86+ (6%) CD20+ B-lymphocytes were identified in the nasal mucosa. No significant differences between allergic and non-allergic individuals were determined. As expected, the data show profound phenotypical differences between circulating peripheral blood and nasal mucosal lymphocytes. Activated memory lymphocytes are present in the nasal mucosa from allergic, but also non-allergic patients and may indicate to a significant role of a local inflammatory state without systemic criteria for allergy. In our study, we show that direct ex vivo isolation of lymphocytes is practicable method and offers a new technique to examine the local nasal allergic immune response using a multiparametric phenotypical analysis. [ABSTRACT FROM AUTHOR]

The direct assessment of T helper (TH)-cell responses specific for antigens is essential to evaluate pathogenic and protective immunity. Presently, analysis and isolation of antigen-specific TH cells is restricted to cells that produce cytokines, or can be performed only with a rare selection of specific peptide major histocompatibility complex class II (MHC II) multimers. Here we report a new method that enables the assessment and isolation of TH cells specific for a defined antigen according to CD154 expression induced after stimulation in vitro. We show that antigen-induced CD154 expression is highly sensitive and specific for human and mouse antigen-specific TH cells. Moreover, the isolation of antigen-specific CD154+ TH cells necessitates only surface staining with antibodies, thereby enabling the fast generation of antigen-specific TH cell lines. Our approach allows assessment of TH cells with a defined specificity for the combined quantitative and qualitative analysis of TH-cell immunity as well as for the isolation of specific TH cells for targeted cellular immunotherapies. [ABSTRACT FROM AUTHOR]

Copyright of Wiener Medizinische Wochenschrift 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.)

The prognosis of patients with malignant melanoma and brain metastases is poor. Therapy of brain metastases is difficult and mostly unsuccessful, with brain metastases being the predominant factor which determines overall survival. We report here on a patient whose brain metastases responded to DTIC+INF-gamma. We present a short summary on the different effects on INF-alpha and INF-gamma and reach the conclusion that clinical trials which combine DTIC and INF-gamma should be performed. Based on this observation, combinations including INF-alpha are not necessarily comparable to modalities which include INF-gamma. [ABSTRACT FROM AUTHOR]

Recently, granulocyte/macrophage-colony-stimulating factor (GM-CSF) became available for overcoming chemotherapy-induced granulocytopenia. GM-CSF not only has a prominent role in the regulation of proliferation and differentiation of haematopoietic cells but it is also secreted by a variety of solid tumours and is capable of exerting growth-stimulatory effects. To evaluate the safety of GM-CSF administration in the treatment of malignant melanoma, we investigated GM-CSF secretion, GM-CSF receptor expression and the effect of GM-CSF on the proliferation of human melanoma cells in vitro. A panel of eight human melanoma cell lines and two fresh tumour specimen was studied. GM-CSF protein was not detectable in culture supernatants by ELISA without stimulation. Interleukin-1 and tumour necrosis factor α induced GM-CSF secretion in all four melanoma cell lines tested. When biotinylated GM-CSF was used, the corresponding receptor was not detectable by immunohistochemical or FACScan analysis. The proliferation of eight human melanoma cell lines and two fresh melanoma specimens was determined by the MTT test after 4-6 days of growth in the presence of different concentrations of GM-CSF (0.1-1000 U/ml). Neither proliferation nor growth inhibition was observed. Therefore the effect of GM-CSF on residual tumour cells in vivo may not present a problem during clinical use to stimulate marrow regeneration after or during chemotherapy of metastatic malignant melanoma. [ABSTRACT FROM AUTHOR]