No story about allergies would be complete without discussing the peculiarly nasty Texas Lone Star tick. It is an aggressive insect which is aroused by the carbon dioxide in the breaths of mammals and it will vigorously pursue its victims. This tick also has vile cousins such as the Castor Bean tick in Europe and the Paralysis tick in Australia.
The Texas Lone Star tick (Amblyomma americanum) is curious because one bite from this insect can induce a permanent allergy to red meat in humans. This allergy cannot be cured and is spreading rapidly across the USA as warmer temperatures encourage this tick’s migration northwards. The allergy can induce a dangerous reaction called anaphylaxis – untreated, this can lead to death, and many thousands of people are afflicted though actual numbers are unclear as it is not a condition American doctors routinely monitor.
The interesting aspect of this allergy is that the allergen (or compound causing the allergic reaction) is specific, well-known and therefore easy to research. The allergen is an oligosaccharide (or complex sugar) called galactose-alpha-1,3-galactose, often shortened to alpha-gal. This sugar is found in the muscles of most mammals, except for monkeys, apes and humans – and alpha-gal is also the reason why organ transplants from animals into humans never work.
In unafflicted people, ingested red meat (including alpha-gal) processes normally through the digestive system with no issues. However, the bite of the Lone Star tick introduces a dose of alpha-gal into the bloodstream and presence of alpha-gal in human blood plasma provokes the production of an antibody called Immunoglobulin M (IgM). The presence of IgM then triggers a robust reaction from a potent antibody called Immunoglobulin E (IgE).
The danger of being allergic to alpha-gal is the body often reacts only after the digestive system has processed the ingested meat, perhaps hours later. So for years, people were keeling over for unknown reasons, resulting in several mysterious deaths of ostensibly healthy people. IgE is normally utilised to immunise the body against parasitic infections from helminths (parasitic worms) such as Schistosoma mansoni, Trichinella spiralis, Fasciola hepatica, etc. Once activated, such immunity exists for life, which is why alpha-gal allergy is incurable, because it becomes part of the body’s range of auto-immune responses.
People with this allergy may also have reactions to fumes arising from cooking meat or skin contact with animals.
So one certainty about allergies is that if an allergen is well-known and universally acknowledged to cause a permanent reaction such as alpha-gal allergy, then it is well worth avoiding the vector of transmission, in this case the Lone Star tick.
Nobody knows why alpha-gal is so fiercely targeted by IgM and then IgE – perhaps it is the shape of the molecule (it has a hydroxyl pair in an odd location). Also, in populations where 20% of people have suffered bites from Lone Star ticks, not everyone bitten actually developed alpha-gal allergy.
The less known
But what if allergens are not well known or established? A classic example would be non-coeliac gluten sensitivity (NCGS) where it is still unclear whether the gliadins in gluten, fructans or FODMAPs (Fermentable, Oligo-, Di-, Mono-saccharides And Polyols) are responsible for the condition. This was investigated in my article, The Strange Story of Gluten.
At first glance, there would not seem much of a connection between house dust mites (HDM) and crustaceans. But studies have indicated an allergic link between them – probably due to a protein called tropomyosin. This protein is also present in mammals and is explained in my article, A Tender Moment.
However, tropomyosins in invertebrates differ in molecular structure from tropomyosin in vertebrates. A 2016 paper researching an increase in crustacean allergies in Singapore suggested the rise was linked to tropomyosin found in HDM. Large scale studies indicate crustacean allergies now affect over 5% of Singaporean teenagers, over 7% of the population of Taiwan and around 7 million Americans.
How this crossover sensitisation occurs may be explained in an earlier 2007 US paper which suggested that invertebrate tropomyosins are digested/decomposed into larger peptide fragments (such as Pepsin A) than meat-based tropomyosins – a peptide is a short chain of amino acids (which are building blocks of proteins).
For HDM, the tropomyosin may have entered the bloodstream via contaminated food or possibly via the nasal cavity. These large peptide fragments in the bloodstream may be detected as foreign bodies, especially by IgE antibodies, thus provoking an autoimmune reaction to the invertebrate tropomyosins. In Singapore, research found 72.4% of crustacean-sensitised children were also sensitive to HDM. Another small study of 95 Canadians had a 90.5% rate of dual-sensitisation.
The strong link suggests that it does not matter if an allergy to HDM proteins led to crustacean sensitivity or the other way around. If you are interested, some problematic HDM species identified are Dermatophagoides farinae and Dermatophagoides pteronyssinus. The allergy to crustacean tropomyosin is the most sensitive allergic reaction known to man – a very tiny amount can trigger deadly anaphylaxis and it is the allergy which sends the most people into hospitals every year.
Gut and general allergens
How the impairment of the human gastrointestinal microbiota (HGM) and a condition called dysbiosis may have an impact on allergies and other even worse conditions is discussed in my article, A Time For Gut Feelings. Also, a comprehensive review of some environmental/food allergens and the hygiene hypothesis is on The Strange Story of Gluten, Part 2.
A 2015 study claimed that human eczema involves only as few as 21 genes in our genome of around 20,000 genes. This is followed by a 2018 paper claiming that hay fever is due to the expression of only up to 41 genes. Hay fever is interesting because it was only first documented in the 19th century. A physician called John Bostock searched the whole of Britain at the time for patients but could only come up with 28 sufferers.
Nowadays, hay fever is an epidemic – and the multitude of hay fever medications on chemist shelves prove it. The oddity is air in most places has been getting cleaner, not dirtier, since the 19th century – this should logically reduce incidences of hay fever. Therefore, even if hay fever has a genetic basis, other factors must be involved as humans have had the same genes for many thousands of years.
The human immune system is a powerful system which prevents infections arising from breaches of the skin, respiratory system or from ingestion of tainted foods. It requires a surprising amount of energy. Battling an infection can raise body temperatures by, say, around 1°C and this will draw 150% of the energy used by a highly energetic organ such as the heart.
In addition, energy is required to produce new antibodies, macrophages and other defensive cells/structures and transport them to the required destinations.
The UK-based Learn Early About Peanut allergy study involved 600+ infants between 4 to 11 months old with severe eczema and/or egg allergy – these subjects are normally prone to also develop an allergy to peanuts in later life.
From 11 months, randomly-selected infants were fed peanuts and overall results collated when they reached age 5. The data was startling. Of the children fed with peanuts, only 3% developed an allergy to peanuts while 17% of the children who had avoided peanuts acquired an allergy to peanuts. The conclusion was therefore: Early avoidance of an allergen is likely to later cause an allergy to the allergen.
Avoidance of allergens may explain the exponential rise in hay fever cases in the modern world. Even in the 19th century, the people most likely to develop allergies were the wealthy, who insulated their homes from the dust and pollen outside. Studies into genetically-related people living in different environments (e.g. urban Finnish and rural Russians of Karelia) also established that urban communities with less exposure to environmental allergens are more likely to develop allergies.
Allergies can occur any time in life and it is curious why immune systems suddenly choose to attack previously benign substances for seemingly no reason. One explanation might be the inherent strength of our immune system, which had evolved to protect humans against challenging environments.
Our Palaeolithic ancestors were nomads, continually encountering wildly-different foods along with bacterial, fungal and parasitic fauna in different locations. Survival relied on strong immune systems capable of constantly countering a broad spectrum of hazards.
It is therefore feasible modern allergen-free environments can result in autoimmune responses being misled and over-sensitised towards compounds which would normally not be threats. The full capacity of an under-utilised immune system can get misdirected towards anything arbitrarily considered foreign or anomalous, even if it is harmless.
A joint US/Australian study into geographic patterns of food allergies has found a link to non-exposure to sunlight (and possibly a deficit of Vitamin D). A lack of sunlight, especially in heavily urbanised areas, causes infants to triple the risk of getting an egg allergy and up to 11 times more risk of a peanut allergy.
Our immune system had evolved in natural environments which were vastly different from the modern, urban conditions most humans now live in. A lack of contact/access to natural allergens/conditions/sunlight is probably a significant driver in the epidemic of modern-day allergies. This is supported by strong links between rising numbers of allergies and urbanisation, though there are still other factors involved.