BSEM – Scientific conference in memory of the late Dr David Freed:
Novelties and Controversies in Allergy and Hypersensitivity.

Some notes on the presentations

Professor Jonathan Brostoff paid tribute to the late Dr David Freed, a long-term member of the BSEM, who did so much for the cause of allergy – and who organised the excellent BSEM conference last year, A tablet a day keeps the patient at bay.

Please click on the links for the individual presentations.

The Role of Lectins in Allergy Dr Amir Ghaem-Maghami
The Role of Adjuvants in Autoimmunity Dr Yehuda Shoenfeld
The relationship between raw milk and atopy Professor C. Braun-Fahrlander
The Cow and the Coronary Margaret Moss
The role of environmental factors in allergy and sensitivity John McLaren Howard
Metals and hypersensitivity reactions Dr Vera Stejskal
Gut mucosal response to food antigens Professor Stephen Challacombe

 

The Role of Lectins in Allergy

Dr Amir Ghaem-Maghami of the Queen's Medical Centre, School of Molecular Medical Sciences in Nottingham.

Dr Ghaem-Maghami's abstract (edited):
The prevalence of allergic diseases has sharply increased during the past few decades and has reached epidemic proportions in many parts of the world. Allergens are a group of proteins that are usually innocuous but can trigger the production of IgE antibodies in genetically predisposed (atopic) individuals which can lead to allergic sensitisation and reactions.

Type 1 IgE-mediated allergic reactions are initiated by the recognition of allergens by cells in the immune system such as epithelial cells (such as make up the skin and the tissue covering the interior and exterior parts of our bodies) and dendritic cells (immune cells, present in many parts of the body but especially the skin, whose purpose it to recognise potential antigens/allergens and 'present' them to other cells in the immune system). Dendritic cells have been shown to play a key role in allergic sensitisation and the triggering of allergic inflammation, but the molecular process is poorly understood. Especially the molecular process by which dendritic cells recognise allergens and how this recognition leads on an allergic reaction.

Dendritic cells use a number of 'receptors', including a number of lectins (proteins which bind to sugars) to recognise allergens. It would appear from both in vitro and in vivo studies, that these receptors may play a key role in allergic sensitisation and may offer a new insights into how allergic sensitation could be modulated.

Notes on the presentation:

In their investigations Dr Ghaem-Maghami's team found that the common C Type lectin receptor appeared to recognise mannan (a polysaccharide or chain of molecules derived from the sugar molecule mannose) and that if they blocked this receptor they could reduce allergic sensitisation by up to 60%. Does this suggest that the mannan was a key element in the recognition of the protein as an allergen and the triggering of the allergic reaction? And could it also have an effect further on in the process?

In their work they applied this theory to the allergic protein DerP1 (housedust mite) and to FelD1 (cat). And in both cases they achieved substantial reduction in the uptake of the allergen and thereby allergic sensitisation/reaction. However, mannan and mannose sugar may not be only sugars involved in this initial recognition or in the subsequent sensitisation.

From the floor:

Dr Sarah Myhill asked whether, in this case, the increase in consumption of dietary sugars during the 20th and 21st centuries could be related to the increase in allergic sensitisation and disease?

First published in July 2012

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The Role of Adjuvants in Autoimmunity

Dr Yehuda Shoenfeld, Head of the Zbludowicz Center for Autoimmune Disease, Chaim Sheb Medical Center at Tel-Hashomer, affiliated to Tel Aviv University, Israel.

Notes on the presentation:

All autoimmune diseases are, in fact, the same disease – it is only their expression that is different – but all are characterised by chronic overstimulation of the immune system. Could adjuvants play some part in this inappropriate stimulation?

The purpose of an adjuvant (a substance that is injected along with a medicine in order to increase its effectiveness), especially when used with vaccines, is both to activate an immune reaction and to cause an inflammatory response. (In terms of a vaccine they are used to enhance the recipient's response so that the amount of injected toxin or bacteria [measles, tetanus, diptheria etc] can be kept to a minimum.)

However, Dr Shoenfeld asked, could the adjuvants, presumed until now to be inert/harmless, themselves be the problem? What he has termed the ASIA (autoimmune/inflammatory syndrome induced by adjuvants) Syndrome? Common to all examples of the ASIA syndrome:

• Complex but very similar clinical manifestations
• Take years to develop
• Appear to result from chronic stimulation of the immune system

Sensitivity to the ASIA syndrome seems to be HLA dependent. (The HLA – human leukocyte antigen – system is the one where the majority of the genes related to the immune system. It lives on chromosome 6 and is essential for immune function.) But HLA dependency only affects around 10% of the population, thus predisposing them to autoimmune conditions should they encounter the appropriate trigger – such as, maybe, an adjuvant.

Question? If the adjuvant is removed, will the patient recover?
The answer appears to be sometimes, depending on whether it has already triggered either genetic changes or an autoimmune condition.

Silicone
Presumed to be inert and a common adjuvant, as well as being used for implants.
Nine cases in Japan where, over a period of six years, of scleroderma, had been triggered by silicone adjuvants while rheumatoid arthritis symptoms appear to have been triggered by silicone implants.

Pandemrix
There was an alarming rise in narcolepsy amongst children in Finland after the widespread vaccination in 2009 against H1N1 swine flu. (See here for more.) All the affected children were in the HLA group.

The only adjuvant used in the vaccine was Squalene A503, the same adjuvant that had been used in the Anthrax vaccine which was administered to all military personnel expected to be deployed (although not all were) in the Gulf War. However, some of both those who had been deployed and who had not, but had been vaccinated, developed the autoimmune condition known as Gulf War Syndrome.

Aluminium
Aluminium is a common adjuvant used in Hepatitis B vaccines and has been connected with the development of both Guillaume Barre Syndrome and multiple sclerosis.

Mercury and thimersol
Used as an adjuvant. Normally it is only its toxic potential that is considered, but it is also an allergen.

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The relationship between raw milk and atopy

Professor C. Braun-Fahrlander, head of the Department of Environment and Health and the Deputy Director of the Institute of Social and Preventive Medicine of the University of Basel

Professor Braun-Fahrlander and her group have been involved in the large number of studies of allergy rates among children brought up on farms in rural Switzerland, all of which appear to suggest that children brought up on farms have a far lower risk of allergy and asthma than those brought up off the farm.

Significant findings from their research:

• Amongst children in the same schools, the children who had the most contact with farm animals had the least allergy.

• Children not living on a farm but playing with farm animals (on friends' families' farms etc) had less allergy than those with no contact with farm animals but more than those living on the farm.

• On small farm, farmers do not buy milk but drink the raw milk from their own cows.

• On small farms, children will come into contact with farm animals from a very early age.

• However, comparison with children living in a Steiner school nearby, not on a farm, but drinking raw milk showed that it appeared to be the raw milk which was the significant factor, as these children had a much lower rate of asthma and allergy even though they were not living on a farm.

• A comparison of bacterial counts in raw milk, boiled raw milk, pasteurised and UHT milks:
Raw milk – 9533
Boiled raw milk – 114
Pasteurised milk – 70
UHT milk – 4.6

However, while there seemed to be no real association between bacterial counts (or fat contents) and asthma and atopy, there was a significant association with high levels of Lactalbumin and Beta Lactoglobulin, both of which are also associated with milk allergy.

• Innate immunity receptors in farm children and for children who had raw milk up to the age of one were up-regulated – although this does not mean that they will have stronger immune systems.

So it would appear that children who drink raw milk will suffer from less asthma and allergy (although those children who only drank whey only suffered from less asthma) although the mechanisms are not yet understood. However, as yet they are not able to 'advise' the consumption of raw milk which may still contain pathogens as that would be seen to be giving 'dangerous' general advice.

One more possibility. Farm children would also be inhaling endotoxins in the farm shed which could possibly provide some protection – although this seems unlikely.

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The Cow and the Coronary

Margaret Moss – MA (Cantab) UCTD (Manchester) DipION CBiol MIBiol, MBANT NTC registered Nutritional Therapy Practitioner

Following on from the work of Doctors Seely, Segall and Grant, and at the request of De Freed, Margaret has spent some time investigating the correlation between high milk consumption and high rates of coronary heart disease (CHD). She will be expounding her theories in more detail for Foods Matter soon but in essence this is what she found:

• To get any meaningful statistics you need to leave a sufficiently wide gap (10-15 years) between the consumption of the milk and the figures for coronary heart disease.

• Times are slightly different in different countries but on average CHD rates appear to drop (or increase, as in Portugal) 10 years after a drop (or increase) in the consumption of milk.

• These figures apply to the consumption of milk only not that to beef, eggs or cheese.

• The availability of good health facilities makes no differenceto the rates of CHD.

• Although there is no direct relationship between wine and milk the comparative figures for wine and milk consumption suggest that wine is healthier!
– Death rates for those drinking relatively little wine or milk – 842
– Death rates for those drinking a lot of wine and not much milk – 473
– Death rates for those drinking a lot of milk and not much wine – 1242

However, should you wish to use wine as an 'antidote' to milk, Margaret's figures sugest that you would need to consume 1.45 litres of wine for every one litre of milk...

• Why?
– Milk has a low magnesium:calcium ratio; calcium competes with magnesium, magnesium reduces clotting.
– Calcium makes the aorta rigid, so that it cannot expand as a reservoir of blood for the heart.
– Milk has a poor ratio of B6, B12 and folic acid to methionine, and so increases homocysteine.
– Milk is low in taurine which helps to maintain a regular heart beat.
– Lactose increases calcium absorption.
– Lactose is broken down to glucose and galactose.
– Galactose is a potent glycator of lipoproteins eg it leads to oxidisation and depsoits of oxidised choesterol in artery walls.

– Bioflavanoids in wine reduce oxidisation

• Wine consumption. It appears that to have a protective effect, wine needs to be consumed with food; wine consumed on its own has little effect.

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The role of environmental factors in allergy and sensitivity

John McLaren Howard, Director of Acumen

• We are all exposed to chemicals (environmental factors), some of which are harmful and some not.

• Chemicals can bind to DNA and can affect the way that the gene operates by overworking it, stopping it working partially or totally, or by preventing it repairing itself.

• DNA methylation provides the instruction patterns for genes but is very easy to disrupt.

• In the laboratory he has separated out the strands of DNA to try to assess where/how the chemical might bind – it may even be hidden within the folds of the structure.

• When exposed to a chemical to which it is sensitised, a lymphocyte (white blood cell) will react, changing, among other things its levels of intracellular calcium.

• Exhaust fumes. When lead was taken out, benzene levels in petrol doubled. But benzene in converts, in the body, into benzoquinone which can block the gene for biotin which is essential for hair growth. In one patient exposure to lead-free petrol resulted in immediate and total hairloss.

• Many other chemicals make DNA adducts (bind in a potentially consecrating way to DNA) and do gene-specific damage. All of these chemicals are freely available in the general environment.

• Only looking at the genome is only half the picture – one also needs to look at the epigenetic changes such as the inhibition of gene repair.

• Epigenetics are changes to the DNA without any change to the DNA sequence; they may be caused by environmental hazards, chemicals; allergies and sensitivities may be relevant. Much work needs to be done.

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Metals and hypersensitivity reactions

Dr Vera Stejskal, Associate Professor of Immunology at University of Stockholm and inventor of the MELISA® metals-sensitivity test.

• Metal allergy is not normally recognised as an allergy as it is not IgE mediated.

• It is assumed that metal sensitivity, such a nickel sensitivity, would only produce a skin reaction but this is not correct; metal sensitivity can cause systemic (whole body) effects/reactions, chronic inflammation, autoimmune and neuro-degenerative diseases including skin conditions such as psoriasis.

• Metals are everywhere – in dental work, medicines, cosmetic, foods, vaccines, body implants.

• Not everyone is sensitive but it is important to discover who is.

• Replacement of dental metals in metal allergic patients is successful (in terms of reducing/eliminating symptoms) in 80% of cases.

• Titanium had always been assumed to be inert but this is not the case; it is a new non-immuno-compatible allergen.

• Titanium cannot be digested by macrophages (the while blood cells that 'eat' potentially damaging foreign bodies in our blood, thus neutralising them) so is transported in the blood to the brain and other organs.

• Titanium or titanium dioxide is very widely used:
– Dental and other body implants
– Many medicines including common diabetic, heart medicines and medicines for conditions such as Parkinsons
– Foods such as cottage cheese and skimmed milk are whitened with titanium dioxide
– Many cosmetics, especially skin whiteners

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Gut mucosal response to food antigens

Professor Stephen Challacombe, Martin Rushton Professor of Oral Medicine
King's College London

• Why are we not all allergic to food? Is food not antigenic (able to produce an allergic response)? Is it antigenic but just not recognised as such? Is it antigenic but only recognised as such by a small number of people?

• The mucosal immune system (the gut) covers 400 square meters (the skin only covers 2 square metres) so there is a massive surface area for absorption. In the small intestine there are few bacteria (many, many, many in the large intestine) but high numbers of lymphocytes (white blood cells) which can produce either pro or anti-inflammatory cytokines (proteins which affect cellular interaction).

• When we ingest food we produce IgA antibodies (to prevent the invasion of pathogens) but we also induce oral tolerance (our gut recognises that it is not toxic or damaging and therefore 'accepts' it) – unless for some reason tolerance is not induced, in which case we get an allergic reaction which can be site specific or systemic.

• The induction of natural oral tolerance (not treatment based) is a new approach to treatment although the mechanism may vary depending on whether the dose is high or low. However, although one can induce tolerance one can also induce stimulation.

• Allergen avoidance is not a successful treatment – specific oral tolerance induction (SOTI) via gradual exposure much more promising. A number of trials on-going although nothing 'solid' yet.

• Probiotics do seem helpful in inducing tolerance.

• Orofacial granuloma (OFG) appears to be similar to oral Crohn's Disease. Could there be a dietary allergen? Around 65% of patients appear to respond to a diet.

• Oral tolerance can be induced at any time of life but appears to be more efficient in the young.

• Sublingual immunisation seems to be the best route as although not as direct as intra nasal immunisation, but, in humans, intra-nasal immunisation is too close to the brain to be safe.

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For more on the BSEM (the British Society for Ecological Medicine) see www.ecomed.org.uk

First published in July 2012

If this article was of interest you will find many other articles on unlikely allergies and allergy connections here – and links to many relevant research studies here.

For more on the more 'mainstream' allergies check in to our 'allergy and intolerance home page' – and for ideas on alternative foods go here.

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