Research Group Anna Nopp

Team Anna Nopp

Research focus

Understanding food allergy development and improving allergy diagnostics and treatment – from technical development to clinical implementation

Allergies are a public health issue that affects over 60 million people in Europe, and especially the prevalence of food allergy is increasing. Development of allergy is affected by different factors like hereditary conditions, method of delivery, exposure to allergens, microorganisms and other environmental factors during pregnancy and childhood.

Within  the program Allergy Development and Prevention Trials (ADAPT) studies aimed at different perspectives of allergic diseases (epidemiology, diagnostics, treatment, basic research) are performed; e.g. diagnostics of parental IgE profiles, influence of pre- and post-natal allergen exposure, investigation of the impact of the immune system during pregnancy, birth and the neonatal period, various treatment strategies, and technical developments for diagnostics and monitoring during different phases of allergy development. The results obtained in this program are expected to improve diagnostics, predict and reduce allergy development in children and provide new treatment strategies for food allergic children.

Group members

Anna Nopp, PhD, Associate Professor, Group Leader
E-mail: anna.nopp@ki.se

The research is focused on improved diagnostic methods for allergy, inflammation and autoimmunity.

 

Caroline Nilsson, MD, Associate Professor
E-mail: caroline.a.nilsson@sll.se

The research is focused on improved diagnostic methods and treatment of food allergies.

 

Joachim Lundahl, MD, Assistant Director of Karolinska University Laboratory, Professor
E-mail: joachim.lundahl@sll.se

The research is focused on inflammation in general with emphasis on the innate cellular response.

 

S.G.O. Johansson, MD, Professor
E-mail: s.g.o.johansson@ki.se

The research is focused on IgE-mediated allergy.

Zekiye Cansu, Laboratory technician
E-mail: zekiye.cansu@ki.se

The work includes immunological methods with special focus on cell culture and flow cytometry.

Ann-Charlotte Sundqvist, Research nurse
E-mail: ann-charlotte.sundqvist@sll.se

The work includes diagnostics and treatment of allergic patients.

Susanne Glaumann, MD, Postdoc
E-mail: susanne.glaumann@ki.se

The research is focused on diagnostics, prognosis and treatment of peanut allergy.

 

Zenib Aljadi, MD, Postdoc
E-mail: zenib.aljadi@ki.se

The research is focused on developing a new method (microfluidic chip) to study basophil functions in inflammation.

Ladan Mansouri, MD, Postdoc
E-mail: ladan.mansouri@ki.se

The research is focused on inflammation and functionality of lymphocytes in patients with chronic kidney disease.

Josef Bradström, MD, PhD-student
E-mail: josef.branstrom@sll.se

The research is focused on diagnostics of nut allergy and oral immunotherapy for treatment of peanut allergy.

Frida Kalm, MSc, PhD-student
E-mail: frida.kalm@ki.se

The research is focused on improving allergy diagnostics using microfluidic chip technology.

Senka Sendic, MD, PhD-student
E-mail: senka.sendic@sll.se

The research is focused on inflammation in patients with chronic kidney disease, mainly IgA nephropathy and SLE nephritis.

Helena Thulin, MD, PhD-student
E-mail: helena.thulin@sll.se

The research is focused on eosinophilic esophagitis among children and adolescents.

Introduction

Allergies are a public health issue that affects over 60 million people in Europe, and especially the prevalence of food allergy is increasing. Food induced allergic reactions vary in severity from mild oral itching to life threatening anaphylaxis, sometimes even within the same patient. Food allergies negatively affect the quality of life for the affected children and their families. Even though the majority of young children who suffer from food allergies to milk, egg and wheat outgrow that specific type of allergy they will still be at risk of later developing other allergic diseases.

Allergy development is multifactorial but heredity and exposure to different factors like allergens, microorganisms and other environmental factors have been given the greatest importance. The time from conception until the baby is one year old is regarded as the time when chronic diseases, including allergies, are established. Health and risk factors for allergy development have previously focused on mode of delivery, diet during pregnancy, the introduction of allergenic foods early in life, intestinal flora and the exposure to animals, drugs and pollution.

IgE-mediated allergy depends on the individual's propensity to form IgE antibodies (IgE-ab) against different allergens e.g. from food and pollen. IgE-ab binds to the surface of mast cells and basophils and subsequent allergen-exposure activates these cells leading to a release of mediators which cause allergic symptoms (Figure 1).

Figure 1. Allergen e.g. peanut crosslinking of IgE-antibodies on the cell surface of basophils and mast results in mediator release and subsequent allergic symptoms.

 

 

 

 

 

 

The diagnostic tools are evolving and today it is possible to analyse IgE-ab against individual components (proteins) of an allergen i.e. component based diagnostics (CRD). CRD gives a high specificity but only show IgE-sensitisation and not necessary true allergy. The diagnostic accuracy has also been improved by cellular in vitro methods. We have developed a method where basophils stimulated in vitro with allergens enables analysis of basophil allergen sensitivity, CD-sens. CD-sens has been shown to significantly correlate with clinical allergic reactions which makes it a valuable alternative to complex in vivo allergen challenges in the airways and orally, and has also been used to monitor treatment effect of anti-IgE (omalizumab) and allergen specific immunotherapy (ASIT).

Today only few treatments of food allergies are available and children with food allergy are mainly encouraged to avoid the food in question. With oral immunotherapy (OIT), very small amounts of the allergen are given in slowly increasing doses until a maintenance dose is reached. Studies have so far shown that OIT leads to desensitization, but it is still unclear whether long-term tolerance is achieved. Allergic reactions, both mild and severe have been a major problem in these studies.

Projects

Development of allergy may be considered as a journey that consists of phases where various factors affects; hereditary conditions, environmental factors during pregnancy, method of delivery, exposure to allergens and environmental factors during the neonatal period and during the child's upbringing. The program “Allergy Development and Prevention Trials (ADAPT)” four cornerstones include studies aimed from different perspectives (epidemiology, diagnostics, treatment, basic research) to generate new knowledge about diagnostics and treatment during the different phases of allergy development (Figure 2).

Figure 2. The four cornerstones of the Allergy Development and Prevention Trials (ADAPT) program (epidemiology, diagnostics, treatment, basic research).

 

 

 

 

 

1. Epidemiology – Follow up two existing multi-generation cohorts to identify markers that might predict allergy development, and to investigate whether diet during and postnatal periods affect allergy development.

2. Diagnostics - Through clinical, immunological and genetic studies combined with innovative technology generate information to improve diagnostics, long term prognosis and monitoring of food allergic children.

3. Treatment - In various treatment studies identify immunologic and genetic factors that might predict treatment outcome and generate new clinical individualized treatment strategies.

4. Basic research - Identifying disease driving mechanisms with focus on IgE and the role of basophils during pregnancy and birth, and the development of allergy or tolerance.

We have shown that CD-sens is a useful complement for complex allergen challenges in vivo with good correlations between CD-sens and SPT-titration, bronchial-, nasal-, and oral- challenge. CD-sens can also be used to monitor treatment with anti-IgE (omalizumab, XolairÒ) and specific immunotherapy. CD-sens with flow cytometric detection is since 2010 implemented both into clinical practice and research for diagnosis and monitoring of treatment efficacy.

15 selected publications

Altered basophil function in patients with chronic kidney disease on hemodialysis
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Aljadi Z, Nopp A, Winqvist O, Russom A, Hylander B, Jacobson S, et al
Clin. Nephrol. 2017 Aug;88(8):86-96

Individually dosed omalizumab: an effective treatment for severe peanut allergy.
Brandström J, Vetander M, Lilja G, Johansson S, Sundqvist A, Kalm F, et al
Clin. Exp. Allergy 2017 Apr;47(4):540-550

IgE to novel citrus seed allergens among cashew-allergic children.
Brandström J, Lilja G, Nilsson C, Ingemarsson N, Borres M, Brostedt P, et al
Pediatr Allergy Immunol 2016 08;27(5):550-3

Basophil allergen threshold sensitivity and component-resolved diagnostics improve hazelnut allergy diagnosis.
Brandström J, Nopp A, Johansson S, Lilja G, Sundqvist A, Borres M, et al
Clin. Exp. Allergy 2015 Sep;45(9):1412-8

Recognition pattern of kiwi seed storage proteins in kiwifruit-allergic children.
Nilsson C, Brostedt P, Hidman J, van Odijk J, Borres M, Sjölander S, et al
Pediatr Allergy Immunol 2015 Dec;26(8):817-20

IgG4 antibodies and peanut challenge outcome in children IgE-sensitized to peanut.
Glaumann S, Nilsson C, Asarnoj A, Movérare R, Johansson S, Borres M, et al
Pediatr Allergy Immunol 2015 Jun;26(4):386-9

Activation of basophils is a new and sensitive marker of biocompatibility in hemodialysis.
Aljadi Z, Mansouri L, Nopp A, Paulsson J, Winqvist O, Russom A, et al
Artif Organs 2014 Nov;38(11):945-53

Successful management of severe cow's milk allergy with omalizumab treatment and CD-sens monitoring.
Nilsson C, Nordvall L, Johansson S, Nopp A
Asia Pac Allergy 2014 Oct;4(4):257-60

The utility of peanut components in the diagnosis of IgE-mediated peanut allergy among distinct populations.
Lieberman J, Glaumann S, Batelson S, Borres M, Sampson H, Nilsson C
J Allergy Clin Immunol Pract 2013 Jan;1(1):75-82

In-vivo extravasation induces the expression of interleukin 1 receptor type 1 in human neutrophils.
Paulsson J, Moshfegh A, Dadfar E, Held C, Jacobson S, Lundahl J
Clin. Exp. Immunol. 2012 Apr;168(1):105-12

Basophil allergen threshold sensitivity, CD-sens, IgE-sensitization and DBPCFC in peanut-sensitized children.
Glaumann S, Nopp A, Johansson S, Rudengren M, Borres M, Nilsson C
Allergy 2012 Feb;67(2):242-7

Basophil allergen threshold sensitivity, CD-sens, is a measure of allergen sensitivity in asthma.
Dahlén B, Nopp A, Johansson S, Eduards M, Skedinger M, Adédoyin J
Clin. Exp. Allergy 2011 Aug;41(8):1091-7

The size of the disease relevant IgE antibody fraction in relation to 'total-IgE' predicts the efficacy of anti-IgE (Xolair) treatment.
Johansson S, Nopp A, Oman H, Ankerst J, Cardell L, Grönneberg R, et al
Allergy 2009 Oct;64(10):1472-7

Passive IgE-sensitization by blood transfusion.
Johansson S, Nopp A, van Hage M, Olofsson N, Lundahl J, Wehlin L, et al
Allergy 2005 Sep;60(9):1192-9

Immunoglobulin E. A new class of human immunoglobulin.
Bennich H, Ishizaka K, Johansson S, Rowe D, Stanworth D, Terry W
Immunochemistry 1968 Jul;5(4):327-8

AllergyAutoimmune diseasesInflammation