Research Group Anna Nopp

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

Research group Anna Nopp

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.

Research group leader

Anna Nopp

PhD, Associate Professor, Group Leader, Director of Doctoral Studies

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

Group members

Caroline Nilsson

MD, Associate Professor

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

Joachim Lundahl

MD, Adjunct professor

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

S.G.O Johansson

The research is focused on IgE-mediated allergy.

Zekiye Cansu

Laboratory technician

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

Ann-Charlotte Sundqvist

Research nurse

The work includes diagnostics and treatment of allergic patients.

Margareta Eriksson

Research nurse

The work includes diagnostics and treatment of allergic patients.

Susanne Glaumann

MD, Postdoc

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

Ladan Mansouri

MD, Postdoc

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

Frida Kalm

MD, PhD-student

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

Senka Sendic

MD, PhD-student

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

Helena Thulin

MD, PhD-student

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

Ulrika Hellberg

RN, PhD-student

The research is focused on asthma and allergy development and association with previous viral infections, immunological markers and gut flora.

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.

Peanut allergen
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.

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).

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 desensitisation, 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).

Allergy Development and Prevention Trials (ADAPT)
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.

Articles

Long-term Follow-up for Missed Cases of Eosinophilic Esophagitis in Children With Previous Foreign Body in the Esophagus.
Thulin H, Nilsson C, Svensson JF, Olén O, Altman M
J Pediatr Gastroenterol Nutr 2021 Jan;Publish Ahead of Print():

Childhood allergy is preceded by an absence of gut lactobacilli species and higher levels of atopy-related plasma chemokines.
Björkander S, Carvalho-Queiroz C, Hallberg J, Persson JO, Johansson MA, Nilsson C, et al
Clin Exp Immunol 2020 Dec;202(3):288-299

Adhesion molecule cross-linking and cytokine exposure modulate IgE- and non-IgE-dependent basophil activation.
Kalm F, Mansouri L, Russom A, Lundahl J, Nopp A
Immunology 2021 Jan;162(1):92-104

A novel tool for clinical diagnosis of allergy operating a microfluidic immunoaffinity basophil activation test technique.
Aljadi Z, Kalm F, Nilsson C, Winqvist O, Russom A, Lundahl J, Nopp A
Clin Immunol 2019 12;209():108268

Individually dosed omalizumab facilitates peanut oral immunotherapy in peanut allergic adolescents.
Brandström J, Vetander M, Sundqvist AC, Lilja G, Johansson SGO, Melén E, et al
Clin. Exp. Allergy 2019 Jul;():

Microfluidic immunoaffinity basophil activation test for point-of-care allergy diagnosis
Aljadi Z, Kalm F, Ramachandraiah H, Nopp A, Lundahl J, Russom A,
J Applied Lab Med. 2019 September

Altered basophil function in patients with chronic kidney disease on hemodialysis
.
Aljadi Z, Nopp A, Winqvist O, Russom A, Hylander B, Jacobson SH, 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 SG, Sundqvist AC, Kalm F, et al
Clin. Exp. Allergy 2017 Apr;47(4):540-550

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

Successful management of severe cow's milk allergy with omalizumab treatment and CD-sens monitoring.
Nilsson C, Nordvall L, Johansson SG, 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 JA, Glaumann S, Batelson S, Borres MP, Sampson HA, Nilsson C
J Allergy Clin Immunol Pract 2013 Jan;1(1):75-82

Basophil allergen threshold sensitivity, CD-sens, IgE-sensitization and DBPCFC in peanut-sensitized children.
Glaumann S, Nopp A, Johansson SG, Rudengren M, Borres MP, 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 SG, Eduards M, Skedinger M, Adédoyin J
Clin. Exp. Allergy 2011 Aug;41(8):1091-7

Passive IgE-sensitization by blood transfusion.
Johansson SG, 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 HH, Ishizaka K, Johansson SG, Rowe DS, Stanworth DR, Terry WD
Immunology 1968 Sep;15(3):323-4