The Blomia tropicalis allergen Blo t 7 stimulates innate immune signaling pathways through TLR2

Abstract

Background

Although the house dust mite species Blomia tropicalis is a leading cause of allergic diseases in tropical and subtropical regions, the identification and characterization of the allergenic proteins remains incomplete.

Objective

We aimed to characterize a recombinant form of Blo t 7 (rBlo t 7) in terms of IgE reactivity, lipid binding activity and ability to stimulate innate immunity.

Methods

The mature Blo t 7 cDNA was cloned by PCR methods for the expression of a secreted form of the allergen in P. pastoris. The IgE reactivity to purified rBlo t 7 as well as the potential cross-reactivity with Der p 7 were determined by ELISA. The lipid binding capacity of rBlo t 7 was assayed using fluorescent lipid probes. The stimulation of TLR2 signaling pathway by rBlo t 7 was examined in cell activation and reporter assays.

Results

The amplified mature Blo t 7 cDNA revealed the presence of a 60 base pair insertion compared with the reference sequence registered in the GENBANK database. Multiple protein sequence alignments of group 7 mite allergens confirmed that this longer deduced amino acid sequence was the authentic Blo t 7 polypeptide chain. Analysis of IgE reactivity can classify rBlo t 7 as an intermediate B. tropicalis allergen which displayed weak cross-reactivity with Der p 7. Purified rBlo t 7 was shown to bind selectively the naturally fluorescent lipid probe cis-parinaric (cPNA) with a dissociation constant of 2 μM. The group 7 Blomia allergen stimulated the TLR2-, NF-kB- and MAPK-dependent production of IL-8 and GM-CSF in respiratory epithelial cells.

Conclusions & Clinical Relevance

Through its propensity to transport fatty acids/lipids and to stimulate TLR2 signaling pathways in airway epithelial cells, Blo t 7 can represent a key allergen for the initiation of the B. tropicalis-induced airway inflammation.

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Guideline compliant prescription of biologicals and possible barriers in dermatological practices in Bavaria

Abstract

Introduction

Psoriasis and urticaria are chronic inflammatory skin diseases, which account for a substantial socio-economic burden and severely affect patients' quality of life. According to the respective German guidelines, biologicals can be used for the treatment of severe forms of these diseases. However, only a minority of patients receive this advised treatment.

Objective

To analyse the prescription of biologicals according to German national guidelines for psoriasis and chronic spontaneous urticaria and to assess possible barriers to prescription.

Material/methods

Cross-sectional, questionnaire based study including all Bavarian dermatologists based in private practices. Linear and logistic regression models were used to identify significant influencing factors on the perception of possible barriers.

Results

Between 01/2017 and 02/2017 a total of 137 (out of 499) dermatologists participated. Of all patients with moderate to severe psoriasis and chronic spontaneous urticaria, participating dermatologists indicated treating 14.2% and 6.9% with biologicals, respectively. The most prevalent barriers to prescription were the high cost of the therapy, the low reimbursement and the fear of recourse. Analysis showed that age, years spent working in a dermatological hospital and the number of patients treated with moderate to severe psoriasis affect the perception of many barriers. Furthermore, age and barriers related to physician factors and external factors were identified as modifiers to the prescription scheme of dermatologists.

Conclusions

The role of clinical education and the importance of external and economic barriers in comparison to medical barriers have to be emphasised. Guideline-compliant use of biologicals has to be optimised. Further research is needed to ascertain not only a barrier pattern for Bavaria, but also for wider settings. Actions based on this for psoriasis are needed to achieve the goal of the WHO Global Psoriasis Report to strengthen the role of patient-centred care and improve the quality of life of affected patients. Analogue, this applies also for urticaria.

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Pigmented fungiform lingual papillae: dermoscopic and clinical features

Abstract

Background

The tongue is covered by fungiform, filiform and circumvallate papillae. Fungiform papillae may be mainly pigmented in dark-skinned individuals.

Objective

A single-center study aimed to examine the clinical and dermoscopic features of pigmented fungiform papulae of the tongue (PFPT) in children, and a concise review of the literature has been performed.

Methods

The clinical and anamnestic data of 8 children affected by PFPT visited at the Pediatric Dermatology Unit of Bologna between 2010 and 2017, and a sistemic review of all studies of PFPT published on Pubmed up to August 31, 2017 have been collected and analyzed.

Results

The results of our data were consistent with the literature review: dark brown to black colored pinhead papules or bumps were observed in all cases of PFPT and three types of clinical patterns have been detected. Moreover the dermoscopic examination showed a cobblestone-like distribution and rose petal pattern. PFPT could be associated with hyperpigmentation of other sites such as the proximal nail folds and gums and an intra-familiar transmission is also possible.

Conclusion

Clinical and dermoscopic features of PFPT may help clinicians to recognize this ethnic, acquired, and benign condition.

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Picosecond Alexandrite Laser for Nevus of Ota Treatment in Chinese

Abstract

Nevus of Ota, also known as nevus fusco-caeruleus ophthalmo-maxillaris, is a benign dermal melanocytosis that typically affects the Asians. The patients experience psychosocial distress related to disfigurement and often seek for treatments. Q-switched lasers have demonstrated positive clinical results.

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Acute vascular reaction due to lipo-prostaglandin E1

Abstract

Lipo-prostaglandin E1 (Lipo-PGE1) is a PGE1 product in lipid microspheres and acts as a vasodilator. Injection of Lipo-PGE1 is used clinically for chronic skin ulcers caused by collagen diseases, diabetes mellitus and impaired blood circulation. Erythema, vascular pain, and phlebitis of the injected sites are recognized as cutaneous manifestations of the side effects of PGE1. Here we present the first case of acute vascular reaction along veins injected with Lipo-PGE1.

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Therapy response was not altered by HLA-Cw6 status in psoriasis patients treated with secukinumab: a retrospective case series

Abstract

Physicians can treat psoriasis patients with several effective treatments, however the response is individual and even the most effective therapies do sometimes not lead to a success of treatment. Currently, possible genetic markers that can predict individual therapy response are investigated. Up to now 45 genes have been identified to be associated with psoriasis [1].

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High immune cell score predicts improved survival in pancreatic cancer

Abstract

Increasing evidence suggests that cancer progression is strongly influenced by host immune response, which is represented by immune cell infiltrates. T-lymphocyte-based immunoscore has proved to be a prognostic factor in colon cancer, but its significance in pancreatic cancer is poorly known. Total of 108 patients operated (R0/R1) for pancreatic ductal adenocarcinoma (PDAC) (TNM stage I–II) were included in the study. Immune cell score (IS) was determined by scoring the samples from grade 0 to 4 according to the number of immune cells (CD3⁺ and CD8⁺) in tumor core and invasion margin using tissue microarrays, immunohistochemistry, and digital analysis. Tumors with microsatellite instability were identified by MLH1 immunostaining. High IS and low histological grade were significantly associated with better disease-specific survival (DSS) and overall survival (OS). The 5-year DSS rate for low, moderate, and high IS groups were 5.0, 15.2, and 33.4%, respectively (p = 0.007). The 5-year OS rate for the low, moderate, and high IS groups were 4.2, 13.4, and 31.5%, respectively (p = 0.004). In addition, IS and prognosis varied within a single TNM stage. There was no association between IS and any of the clinicopathological variables. IS was shown to be an independent prognostic factor for better DSS and OS in multivariate analysis, together with the histological grade of the tumor and perineural invasion. Five MLH1-negative tumors (4.6%) were found showing no correlation with IS. IS could be a useful prognostic marker in patients with PDAC treated by primary surgery.

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