foto

Prof. dr. R. van Ree

Position
Professor
Main activities
Research
Specialisation
Molecular and Translational Allergology
Focus of research
Research of the group of Ronald van Ree focuses on a number of inter-related basic and translational questions around IgE-mediated allergies, also referred to as type I allergies. The four major pairs of basic (B1-B4) and translational (T1-T4) questions addressed are:

Basic research:

B1 - What makes a protein an allergen?

This topic focuses on the role of intrinsic physico-chemical properties (such as protease resistance and type of post-translational modifications) and functional properties of proteins (enzymatic activity, ligand binding, PRR-binding) in shaping the process of sensitization and the induction of symptoms.

B2 - How is the process of sensitization regulated?

Obviously this question has overlap with the question “what makes a protein an allergen”, but it has a broader scope. The intrinsic properties of a protein are just part of the equation. On top of that, timing and level of exposure as well as the context in which the exposure takes place (environmental co-exposures such as pollutants, infections, exposure to non-pathogenic micro-organisms, diet, lifestyle, affluence) have impact on the process of skewing towards tolerance or sensitization and clinical disease.

B3 - Which biomarkers can discriminate different clinical phenotypes?

This topic centers on finding biomarkers for tolerance and clinical allergy, and within the latter, for symptom severity? Accurate phenotyping is of great importance to understand disease mechanisms and develop strategies for personalized treatments.

B4 - What is the mechanism of immunotherapy?

Allergen-specific immunotherapy is the only causal treatment of IgE-mediated allergies. Despite the fact that it has been used for over a century now, its mechanism still is not completely clear. Certainly the topic has overlap with the question what makes healthy subjects tolerant to allergens. Better insight in the mechanism of tolerance induction may help improve strategies for immunotherapy, but also for primary prevention.

Translational questions:

T1 - Can we predict the allergenic risk of proteins?

This topic deals with the question whether it is possible to predict if exposure to novel proteins will pose an increased risk of sensitization and symptom elicitation in an atopic population having established allergies or being prone to develop them. Can we establish a risk profile of a novel protein based on its intrinsic physico-chemical and functional properties and the context of exposure? A reliable evidence –based prediction algorithm would be of great importance for protocols to evaluate the allergenic risk transgene candidates for genetically-modified food crops.

T2 - Can we develop strategies to prevent sensitization?

The longstanding paradigm of prevention by avoidance of exposure to allergens is under serious scrutiny. This development has initially been based on epidemiological observations. High allergen exposure in the first year of life is now slowly gaining support as a better way forward for prevention. This hypothesis needs confirmation in randomized placebo-controlled intervention studies. Also factors linked to the context of exposure to allergens have provided new leads for primary prevention. These factors include the intensity, frequency and chronicity of early childhood infections, gut microbiota composition, dietary composition (vitamins, fatty acids, etc.), environmental co-exposures (non-pathogenic micro-organisms) and (sedentary indoor) life-style. Mechanistic studies (human in vitro and animal models) have to pave the way towards intervention studies.

T3 - How can we improve performance of diagnostic tests?

In vitro diagnostic tests for specific IgE antibodies are used to support the diagnosis of IgE-mediated allergies. These tests have for more than four decades been based on extracts of allergen sources. These tests have always had problems with sensitivity (important allergens under-represented in extracts) and specificity (detection of IgE without clinical relevance). Molecular allergology has now provided the tools to improve this situation. Important allergens can now be produced as recombinant reagents and evaluated for diagnostic purposes. Epidemiological surveys and diagnostic clinical trials are needed to establish which allergens are responsible for which clinical phenotypes. Based on this knowledge, molecular diagnostic tests can be developed to replace extract-based tests.

T4 - How can we improve safety and efficacy of immunotherapy?

As is true for allergy diagnostics, allergen-specific immunotherapy is performed with allergen extracts. This therapy is effective but has a serious risk of (allergic) side-effects. In addition, the current therapy requires 3 to 5 years of monthly injections to achieve its long-lasting effect. The challenge is to make immunotherapy safer and more effective, in particular in the sense of shortening the therapy significantly. Molecular allergology has provided the opportunity to design hypo-allergenic recombinant versions of the most important disease-related proteins, the so-called major allergens. In addition, these molecules can be selected for increased immunogenicity and combined with novel adjuvants that effectively induce protective anti-inflammatory immune skewing. These approaches need to be evaluated in first-in-man clinical trials, and subsequently evaluated for superiority to current treatment, both with respect to safety and efficacy.

The research group of Ronald van Ree works on all of the above described research topics. It does so using four major research disciplines: epidemiological surveys, mouse models, clinical trials and human in vitro immunology.

Key publications
  • Gao ZS, Yang ZW, Wu SD, Wang HY, Liu ML, Mao WL, Wang J, Gadermaier G, Ferreira F, Zheng M, van Ree R, Peach allergy in China: A dominant role for mugwort pollen lipid transfer protein as a primary sensitizer. J ALLERGY CLIN IMMUN 2013;131 (1):224-226 [PubMed]
  • Burney PGJ, Potts J, Kummeling I, Mills ENC, Clausen M, Dubakiene R, Barreales L, Fernandez-Perez C, Fernandez-Rivas M, Le TM, Knulst AC, Kowalski ML, Lidholm J, Ballmer-Weber BK, Braun-Fahlander C, Mustakov T, Kralimarkova T, Popov T, Sakellariou A, Papadopoulos NG, Versteeg SA, Zuidmeer L, Akkerdaas JH, Hoffmann-Sommergruber K, van Ree R, The prevalence and distribution of food sensitization in European adults. ALLERGY 2014;69 (3):365-371 [PubMed]
  • Datema MR, Zuidmeer-Jongejan L, Asero R, Barreales L, Belohlavkova S, de Blay F, Bures P, Clausen M, Dubakiene R, Gislason D, Jedrzejczak-Czechowicz M, Kowalski ML, Knulst AC, Kralimarkova T, Le TM, Lovegrove A, Marsh J, Papadopoulos NG, Popov T, del Prado N, Purohit A, Reese G, Reig I, Seneviratne SL, Sinaniotis A, Versteeg SA, Vieths S, Zwinderman AH, Mills C, Lidholm J, Hoffmann-Sommergruber K, Fernández-Rivas M, Ballmer-Weber B, van Ree R, Hazelnut allergy across Europe dissected molecularly: A EuroPrevall outpatient clinic survey. J ALLERGY CLIN IMMUN 2015;136 (2):382-391 [PubMed]
  • Smith M, Jäger S, Berger U, Sikoparija B, Hallsdottir M, Sauliene I, Bergmann KC, Pashley CH, de Weger L, Majkowska-Wojciechowska B, Rybníček O, Thibaudon M, Gehrig R, Bonini M, Yankova R, Damialis A, Vokou D, Gutiérrez Bustillo AM, Hoffmann-Sommergruber K, van Ree R, Geographic and temporal variations in pollen exposure across Europe. ALLERGY 2014;69 (7):913-923 [PubMed]
  • Santos A, van Ree R, Profilins: Mimickers of Allergy or Relevant Allergens?. INT ARCH ALLERGY IMM 2011;155 (3):191-204 [PubMed]
All Publications
Curriculum Vitae

Ronald van Ree was originally educated in history but switched to biochemistry and immunology, the field in which he defended his thesis at the University of Amsterdam in 1994 on the topic of grass pollen allergens and their interaction with the immune system. From 1994 until 2005 he headed the Allergy Research Laboratory at Sanquin Blood Supply Foundation in Amsterdam. In July 2005 he moved to the Academic Medical Center in Amsterdam where he was appointed as Associate Professor at the Department of Experimental Immunology. There he is head of the Laboratory for Allergy Research. In June 2009 Ronald van Ree was appointed as Full Professor of Molecular and Translational Allergology. The main areas of interest of the Allergy Research group are:

 

 Protein-chemistry and molecular biology of respiratory and food allergens: what makes an allergen an allergen?
 Innovative approaches for in vitro and in vivo diagnosis of IgE-mediated allergy: from allergen extracts to molecular diagnostics.
 Innovative biopharmaceutical approaches for allergen-specific immunotherapy: recombinant technology, novel adjuvants and administration routes.
 Immuno-epidemiology of respiratory and food allergies: the role of allergen exposure, environment, diet, infections and lifestyle in the development of allergy.
 Mouse models of allergy and asthma: how are sensitization and disease expression regulated?

 

Ronald van Ree has participated in many EU Framework Program projects, amongst which as co-ordinator of the CREATE project (FP5) developing certified reference materials for allergen products, as vice-coordinator in the Integrated Project (FP6) on Food Allergy, EuroPrevall, in the GLOFAL project (FP6) aiming at integrating food allergy research in developing countries in EU framework program, as co-ordinator of the ongoing project (FP7) on immunotherapy for food allergy FAST (2008-2015), and more recently as ExCom member of the iFAAM project (FP7) on risk management of food allergy. In February 2014 he has taken up the coordinatorship of a new recently granted EU project BM4SIT targeting at innovative approaches for allergen-specific immunotherapy (novel adjuvant in combination with a designed hypo-allergen). He is on the editorial board of several leading journals in the field of allergology, and is associate editor of International Archives of Allergy and Immunology. He is the academic co-chair of the HESI-PATC. Ronald van Ree has published around 275 papers in peer-reviewed journals, and several book chapters.

Ronald van Ree serves as consultant for HAL Allergy BV (Leiden; www.hal-allergy.com) and Citeq BV (Groningen; www.citeqbiologics.com)

Research programmes

Molecular mechanisms of disease induction, symptom expression, immunotherpay and prevention in IgE-mediated allergy

The main areas of interets of the Allergy Reserach group are:

  • Protein-chemistry and molecular biology of respiratory and food allergens: what makes an allergen an allergen?
  • Innovative approaches for in vitro and in vivo diagnosis of IgE-mediated allergy: from allergen extracts to molecular diagnostics.
  • Innovative biopharmaceutical approaches for allergen-specific immunotherapy: recombinant technology, novel adjuvants and administration routes.
  • Immuno-epidemiology of respiratory and food allergies: the role of allergen exposure, environment, diet, infections and lifestyle in the development of allergy.
  • Mouse models of allergy and asthma: how are sensitization and disease expression regulated? 


Theme: Infection and Immunity / Public Health and Epidemiology
 

This research group participates in CIA

Faculty
Prof. dr. R. van Ree

Postdocs
Dr. J.H. Akkerdaas
Dr. ir. L.S. van Rijt
Dr. L. Zuidmeer

PhD Students
S. Busold
Drs. M.R. Datema MSc
F.M.J. Hafkamp
N.A. Nagy
Drs. H.J.M. Warmenhoven MSc
Z. Gao PhD
S.A. Lyons MSc (UMCU)

Others
A. Logiantara
S.A. Versteeg

Other research related activities
  • Other, European Academy of Allergy and Clinical Immunology
  • Membership of editorial board / Editorship, CLINICAL AND TRANSLATIONAL ALLERGY
  • Membership of medical or scientific committee, WHO/IUIS, WHO/IUIS Allergen standardization Committee
  • Membership of medical or scientific committee, WHO/IUIS, WHO/IUIS Allergen Nomenclature Committee
  • Contribution to guidelines and protocols, Food Allergy and Anaphylaxis Guidelines / European Academy of Allergy and Clinical Immunology
  • Membership of medical or scientific committee, HESI-ILSI, Protein Allergenicity Technical Committee (co-chair)
  • Membership of advisory board / Consultant, HAL Allergy BV
  • Membership of advisory board / Consultant, Citeq BV
  • Membership of advisory board / Consultant, Angany Inc.
Current research funding
  • Europese Unie
  • HAL Allergy bv
  • ILSI Health and Environmental Sciences Institute
  • NWO