News
Identification of new effector B cell subgroups and their role in allergic diseases
B cells play an important role in the human immune system because they are the cells that produce antibodies. A research team at SIAF led by Professor Cezmi Akdis (Workpackage 2) recently reported that B cells – apart from their role antibody-producing cells – can function as regulators of the immune response by the production of cytokines. Certain subgroups of B cells were identified which produce specific cytokines. For instance, regulatory B cells produce the anti-inflammatory cytokine interleukin-10 and are hence able to protect against autoimmune diseases and allergic inflammation.
The aim of this study is to identify new human cytokine-producing B cell subgroups and research their role in immune regulation. B cells cannot be cultured for lengthy periods in vitro. Therefore we suppressed the cell division of the B cells by increasing the production of two specific genes (BCL-6 and BCL-xL). The method of suppressing cell division and increasing the production of certain proteins is known as over-expression. This makes it possible for us to form long-lived B cells. To enable us to characterise individual B cells, we isolated individual cells and generated B cell clones. Then we studied the gene activity of these clones in detail by means of next-generation sequencing (determining the nucleotide sequence of the RNA).
To allow us to identify new effector B cell subtypes that produce specific cytokines, we had to group the individual B cell clones based on their cytokine expression. Using this approach we identified 6 clone groups which expressed specific cytokine profiles, i.e. activated specific cytokines. Some of these cytokine profiles (an expression profile shows what the cell actually does) resembled previously described subgroups of effector B cells, such as the interferon-gamma-producing B cells and the interleukin-10-producing regulatory B cells. Interferon is a protein that exerts an immunostimulating, primarily antiviral effect; interleukin is a cytokine with an anti-inflammatory effect, which inhibits the inflammatory reactions taking place in the body. In addition, we found other clusters with different cytokine profiles, which have not previously been described. At present we are working on carrying out detailed characterisation of these new B cell subgroups so that their potential role in allergic diseases can be assessed.
“Scientific Allergy” magazine – No. 3/2016
With “Scientific Allergy” CK-CARE provides themed issues of the magazine in a loose sequence. These present current findings from allergy research for primary care providers in general practice and paediatric practice. However, “Scientific Allergy” may also be displayed in practices to provide information for patients.
In issue No. 3 you will find, among other items, practical tips on the right course of action in “Anaphylaxis – how to detect anaphylaxis quickly and react correctly” and articles on subjects such as “Allergy prevention – how you can advise parents”, “Allergen-specific immunotherapy – when is ‘hypersensitization’ advisable?”.
It is our declared aim to increase knowledge about allergic diseases. We feel sure that “Scientific Allergy” will inspire people to engage intensely with allergic diseases and utilise advances in research for the benefit of allergy sufferers.
In vivo study proves: low-molecular, non-allergenic pollen compounds enhance the allergen-specific immune response in humans
A scientific team led by Dr. Stefanie Gilles, Dr. Isabelle Beck and Professor Claudia Traidl-Hoffmann (Member of the Board of Directors and Coordinator in Workpackage 1 of CK-CARE) from the university Department of Environmental Medicine, demonstrated in vivo the clinical relevance of low-molecular pollen compounds with the aid of skin prick tests and nasal provocation tests.
The researchers tested effects of allergens from birch and grass pollen with and without the addition of low-molecular pollen compounds
During the course of the study, skin prick tests and nasal provocation tests were performed on healthy and allergic subjects. Allergens from birch and grass pollen were used for the tests. The pollen allergens were prepared for testing either in a saline solution or with a low-molecular fraction of the pollen extract. The skin prick tests then produced a stronger allergic immune reaction (wheals, redness) when the low-molecular pollen fraction was added. In the nasal provocation tests, the low-molecular pollen compounds increased the local release of interleukin-8 (IL-8) and immunoglobulin E (IgE). Increased production of nasal discharge was observed in the study group in which the low-molecular pollen fraction was added. More severe runny nose and itchy eyes, an increased urge to sneeze and other intensified symptoms were also observed. Healthy subjects did not react measurably to the pollen compounds in the study neither in prick tests on the skin nor in nasal provocation tests.
The results of the study might alter allergy diagnostics and allergen-specific immunotherapy
With this pilot study, the research team led by Gilles has done crucial groundwork for future clinical trials, which should investigate in more depth the effects of low-molecular, non-allergenic compounds from pollen. Non-allergenic compounds might be of clinical relevance, especially in allergy diagnostics and in allergen-specific immunotherapy (“hyposensitization”) because pollen extracts are currently being used in these areas. Whether these extracts currently in use contain pro-inflammatory substances and in what quantities has not yet been adequately investigated.
The Publikation entitled “Pollen derived low molecular compounds enhance the human allergen specific immune response in vivo”, which appeared on 04.2016 in the journal Clinical and Experimental Allergy, will therefore be significant for future clinical research in the allergy field.
Davos Declaration No 3
Instigated by CK-CARE (Christine Kühne – Centre for Allergy Research and Education), the Global Allergy Forum has now been held in Davos for the third time. From 28 June until 1 July, some 70 world-renowned scientists in the field of allergology and its allied disciplines convened to discuss challenges and possible solutions in the field of atopic dermatitis/eczema.
The results and findings are summarised in the third “Davos Declaration” and published in the journal ‘Allergy’. It reflects the current state of research, education, healthcare and knowledge transfer, as well as put forward concrete proposals for improving the situation in allergology.
Successful interdisciplinary cooperation between microbiology and allergology – from field research to cutting edge molecular biology
Pollen has a specific microbiome for every plant species!
The number and severity of diseases based on pollen allergies is constantly increasing. Scientists now assume that plants’ own defence mechanisms against environmental factors, such as exhaust fumes or adverse microbial overload, bear a significant share of the allergenicity of pollen and pollen-associated compounds. It is important to understand that microbes in themselves do not have a negative impact on plants (and people). Instead, the “right mix” (diversity) of microbes appears to be crucial to the health of human, animal and environment. The publication quoted below first describes the different types and number of microbes to be found on birch and grass pollen. The differences in the pollen microbiome between different species of plant are described as well as the differences between the pollen microbiome of the same plant species, but under the influence of different environmental factors such as location and pollution burden. In a second step, possible correlations between air pollution, pollen microbiome and the allergenicity of pollen were established.
If we damage the environment less, the allergenicity of plant pollen will also decrease
In this connection the research team established that precisely air pollution (traffic load) and a “harmful microbial load” have a negative influence on the allergenicity of pollen – hence more allergen is released. The aim now is to understand what induces pollen to release more allergen and what microbes act as trigger factors in this process. It seems clear that allergen production and allergen release are a defensive reaction – a type of stress situation that is intended to ensure the plant’s survival. A more positive influence on the plant world is needed in future through sustainable management of the environment, so that plants produce less (disease-causing) pollen allergen and hence patients have fewer symptoms and fewer allergies arise.
In February 2016, for the field of medicine, the relevant publication “Pollen-Associated Microbiome Correlates with Pollution Parameters and the Allergenicity of Pollen“ (first author: Andrea Obersteiner) was successfully published in the internationally highly-ranked specialist journal PLOS One. The publication is the result of excellent interdisciplinary cooperation between the Institute for Environmental Medicine at UNIKA-T and the Department of Microbe-Plant Interaction at the Helmholtz Centre in Munich. The scientific colleagues at the Institute for Environmental Medicine, Stefanie Gilles, Isabelle Beck and Franziska Häring, and the Institute Director Claudia Traidl-Hoffmann are pleased that, through their research efforts, they have made a unique contribution to the understanding of the connection between microbiome, air pollution and the allergenicity of pollen.
“Global Allergy Forum” – International think tank on the subject of allergies
Instigated by CK-CARE (Christine Kühne – Centre for Allergy Research and Education), the Global Allergy Forum has now been held in Davos for the third time. From 28 June until 1 July, some 70 world-renowned scientists in the field of allergology and its allied disciplines convened to discuss challenges and possible solutions in the field of atopic dermatitis/eczema.
Atopic dermatitis is the most widespread chronic inflammatory skin disease. Among allergic disorders, atopic dermatitis is considered to be a model disease. However, in children that are affected, a significant proportion (approx. 40%) experience healing before the onset of adolescence. It is believed that this natural healing is at least partly attributable to as yet undiscovered mechanisms that lead to an immune tolerance of environmental factors like allergens. To date, such mechanisms have not yet been investigated systematically. Research in this area will exert a direct impact on the quality of life of patients.
Divided into six working groups, the participants at the GAF 2015 analysed current problem areas such as environmental factors, particularly their impact on the bacterial flora (microbiota) of the skin, the development and course of atopic diseases, plus prevention strategies.
In the “Psycho-Neuro-Immunological Aspects/Itching” working group, the importance and problems of itching as a primary symptom of atopic dermatitis was a clear-cut subject for elaboration. Compared with pain research, there are major shortcomings in the research undertaken into itching. Itching as a dimension of suffering is not taken seriously by many non-sufferers, nor by society. Progress however can be expected by imaging methods that can visualise the processing of itching by the brain; the same methods have also revealed surprising results about the involvement of hitherto unsuspected regions of the brain in this sensation.
In their investigation of environmental factors, the “Environment/Microbiota” working group looked into outdoor air pollutants but also focused on cutaneous microbiota. Here, a great deal of research work is still undertaken into individual differences, into the actual role of skin surface microbes (“beneficial or harmful”) as well as into the potential therapeutic implications of external applications of probiotic bacteria to support anti-inflammatory therapies. Even the relationship between dietary intake, the gastro-intestinal tract and skin microbiota constitutes a new research area.
The “Skin Barrier” working group built on the rapid progress made in recent years; in particular the discovery that, as a result of specific mutations, dryness of the skin and barrier dysfunctionalities can be attributable to genetic factors; (i.e. a mutation in the gene for the epidermal protein filaggrin will lead to a high predisposition to the development of atopic eczema). The group called for further research into an improved and standardised measurement of barrier functions in daily clinical routines as well as intervention studies into correcting malfunctioning barriers (keyword: skin care).
The “Epidemiology and Standardisation” working group turned its attention to epidemiological research methods, where improvements to measuring instruments would lead to a better diagnosis of the disease but also to measurements of the severity of the eczema. The starting point for such investigations should be a database for neurodermatitis at a population level. Such a database does not yet exist. The clear definition of subgroups in the disease as well as an understanding of the roles of prenatal influences and the effects of various intervention programmes appears to be equally important. A need for healthcare research in the field of neurodermatitis appears to be pressing. There is also a lack of basic epidemiological knowledge in the medical profession.
In the “Immune Deviation” working group the importance of immunological but also pharmacological research to correct and remedy aberrant immune responses was underscored. The scope of this critical research also extends to the examination of comorbidities, i.e. the simultaneous emergence of other diseases. New therapeutic approaches also include biologics, i.e. an antibody against the interleukin 4 receptor, as well as inhibitors of kinases and phosphodiesterases. The induction of immunological tolerances to common allergens remains a long-term objective. Encouraging results in allergen-specific immunotherapy (desensitisation) and in neurodermatitis have already been achieved.
A further group addressed the enormous chasm between the scientific progress that has been made in dermatology and allergology and the translation of this knowledge in the everyday work of doctors and the lives of patients. There is a lack of information for key target groups such as physicians, healthcare professionals, patient organisations and, not least, political decision-makers. That’s why it is imperative to improve educational activities at all levels and for a multitude of target groups. The aim of the discussions in this working group was to arrive at concepts and actions that would close this information gap.
The results and findings of the 3rd Global Allergy Forum are summarised in the third “Davos Declaration”. It reflects the current state of research, education, healthcare and knowledge transfer, as well as put forward concrete proposals for improving the situation in allergology.
