Publication date: Available online 17 January 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Fabio R. Melo, Ola Wallerman, Aida Paivandy, Gabriela Calounova, Ann-Marie Gustafson, Benjamin R. Sabari, Giuliano Zabucchi, C David Allis, Gunnar Pejler
BackgroundMast cells are key effector cells in allergic reactions. When activated to degranulate, they release a plethora of bioactive compounds from their secretory granules, including mast cell-restricted proteases such as tryptase. In a previous study we showed that tryptase, in addition to its intragranular location, can be found within the nuclei of mast cells where it truncates core histones at their N-terminal ends.ObjectiveConsidering that the N-terminal portions of the core histones constitute sites for posttranslational modifications of major epigenetic impact, we here evaluated whether histone truncation by tryptase could have an impact on epigenetic events in mast cells.MethodsMast cells were cultured from wild type and tryptase null mice, followed by an assessment of their profile of epigenetic histone modifications and their phenotypic characteristics.ResultsWe show that tryptase truncates nucleosomal histone 3 (H3) and H2B and that its absence results in accumulation of the epigenetic mark, lysine 5-acetylated H2B (H2BK5ac). Intriguingly, the accumulation of H2BK5ac was cell age-dependent and was associated with a profound upregulation of markers of non-mast cell lineages, loss of proliferative control, chromatin remodeling as well as extensive morphological alterations.ConclusionThese findings introduce tryptase-catalyzed histone clipping as a novel epigenetic regulatory mechanism, which in the mast cell context may be crucial for maintaining cellular identity.
To estimate the number of patients with recurrent respiratory papillomatosis currently managed in secondary and tertiary health care in the UK and the frequency of its treatment with radiofrequency cold ablation (Coblation™).
Cross-sectional survey of ENT consultants in the UK with validation using Hospital Episode Statistics (HES) inpatient data.
Online survey.
ENT consultants in the UK.
Number of recurrent respiratory papillomatosis patients currently managed in acute care in the UK and frequency of use of Coblation.
A total of 283 ENT consultants from 128 UK NHS healthcare trusts and health boards completed the online survey. Responses were received from 86% of surveyed organisations, and an estimated 45% of all ENT consultants in UK. The estimated number of recurrent respiratory papillomatosis patients from the cross-sectional survey was 918 (at August 2015) which included 730 patients in England. The number of recurrent respiratory papillomatosis patients in England estimated from Hospital Episode Statistics (2014/15 financial year) was up to 741. A total of 42 Coblation procedures conducted in the UK were identified from the cross-sectional survey; 36 were conducted in England compared with 34 identified from Hospital Episode Statistics.
The numbers of recurrent respiratory papillomatosis patients and Coblation procedures identified in England from a cross-sectional survey and Hospital Episode Statistics were in broad agreement. Our study estimated 1.42 recurrent respiratory papillomatosis patients per 100 000 in the general UK population. We also estimated that Coblation procedures accounted for 3% of interventional treatments conducted in the UK recurrent respiratory papillomatosis population.
A 32-year-old man presented with a 2-year history of multiple brownish macules on his trunk. There were no symptoms, such as itching or pain, and the lesions continuously spread. He felt the lesions become elevated when he drank alcohol. The physical examination revealed multiple brownish macules exclusively on his trunk (Fig 1). There were no changes induced by physical stimulation. A biopsy specimen was obtained, and the histopathologic examination revealed basal hyperpigmentation with a lentiginous pattern and a dense infiltrate composed of cuboidal-shaped cells and eosinophils in the superficial dermis (Fig 2).
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A 33-year-old Pakistani man presented with multiple reddish, hypopigmented macules on his chest and back (Fig 1). The lesions appeared 20 years earlier and had progressively increased in number. Flat-topped papules were present over his hands and shins (Fig 2). There was no growth on fungal culture from skin scrapings and no response to topical terbinafine treatment. His parents were cousins, but there was no family history of similar conditions. Blood tests, including a complete blood cell count, HIV, and lymphocyte subsets were normal.
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