Reflecting on 30 years of research and paradigm shifts around the major house dust mite allergen

2018 - 09 - 27

Der p 1, a cysteine protease from the house dust mite that can cause allergy, was the very first allergen to be identified by biologists. The cloning of its cDNA in 1988 marked the emergence of a new investigation field in allergy research: molecular allergology. At the occasion of the 30th anniversary of Der p 1 cloning, Dr Andy Chevigné, Principal Investigator at LIH, was invited to co-author a review on past and future research on Der p 1 for the Journal of Allergy and Clinical Immunology, the highest ranked journal for allergy research.

Der p 1 is the most abundant allergen contained in faecal pellets of the house dust mite. It is introduced into the body by inhalation and causes inflammation of the airways. Although it was cloned as the first allergen three decades ago, its biological role as a cysteine protease remains largely elusive. Its substrates at the level of the airway mucosa where it accumulates and the immune pathways triggered by the degradation of substrates are also not studied to detail yet.

Dr Andy Chevigné worked on the characterisation of Der p 1 during his PhD carried out jointly between the University of Liège and the Free University of Brussels, Belgium, under the supervision of Dr Alain Jacquet (now affiliated with the Chula Vaccine Research Centre at the Chulalongkorn University in Bangkok, Thailand). At present he is Principal Investigator in the Immuno-Pharmacology and Interactomics research group at LIH’s Department of Infection and Immunity. This department has a strong research focus on molecular allergology made evident amongst other by its significant contribution to the very first Molecular Allergology User's Guide published in 2016 by the European Academy of Allergy and Clinical Immunology (EAACI).

Dr Chevigné always kept a strong connection to his former research team and is still collaborating with Dr Jacquet on the functional role and allergenicity of Der p 1. Both scientists had the opportunity to summarise the current knowledge on Der p 1 in a review entitled “Emerging roles of the protease allergen Der p 1 in house dust mite-induced airway inflammation”. The article appeared in the “Paradigms and Perspectives” section of the August 2018 issue of the Journal of Allergy and Clinical Immunology (impact factor 2017: 13.25).

The first part of the article reviews and discusses the past findings on allergen structure and function and the successive paradigm shifts associated with Der p 1. The second part lists the current challenges and open questions in Der p 1 research and speculates about the possible next steps leading to advances in the field. The difficulties to isolate and correctly purify Der p 1 from mite extracts had rendered the characterisation of the allergic pathways difficult and slow. It is now known that Der p 1 degrades various protein types on the apical surface of airway mucosa, activates other dust mite allergens and ultimately stimulates a Th2 allergic response. Yet it is not clear whether innate immune receptors or receptors of the airway epithelium are among the targets of the protease. The authors therefore propose to apply a holistic approach to identify the complete repertoire of Der p 1’s cellular targets. The conduct of a “degradomics” study could allow unravelling the different pathways triggered by the allergen and greatly expand the current knowledge.  

Before jointly editing this review, Dr Chevigné and Dr Jacquet had already co-authored eight publications on the research topic, including a review in 2014 on the activation mechanisms of protease allergens and a research article in 2017 on the substrate specificities of protease allergens and the human cell surface proteome cleaved by Der p 1. Dr Jacquet had also been invited to Luxembourg to give a presentation on his research focus last year in the frame of the International Symposium on Molecular Allergology ISMA 2017 co-organised by EAACI and LIH’s Department of Infection and Immunity with Prof Markus Ollert acting as chair and Dr Christiane Hilger as local coordinator.

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