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The Science behind Allergy

The Lectin Group

Dr David L. J. Freed, MB, MD, MIBiol


I joined the Department of Microbiology at Manchester University in 1969, straight after my house jobs, as Assistant Lecturer, and after a year rotating through its various subspecialities I settled into immunology which at the time seemed the most glamorous. I fell in love with research and that love affair has lasted ever since, but as I did not want to lose my clinical skills I also attached myself voluntarily to the immunology clinic at Manchester Royal, the main clinical fare of which was allergy.

Manchester was pretty advanced in the sixties, with a consultant immunologist of its own (Geoffrey Taylor) who was also the Reader in immunology in my department. Final year medical students were given one whole hour’s lecture devoted to allergy! I followed in Geoff Taylor’s footsteps and devoted my first seven years to cancer immunology, on which I wrote my MD thesis. It was in that arena that I first heard of lectins, those enigmatic plant proteins that agglutinate animal red cells just as antibodies do, with similar specificities and avidities, and (we were beginning to learn) also had profound cytotoxic effects against cancer cells in vitro. Lectins recognise and bind to specific carbohydrate motifs (aka determinants, epitopes, haptens) on the surface glycoconjugates of cells and tissue proteins, much as a blood-group antibody binds to its specific carbohydrate hapten. Indeed, before the advent of monoclonals, lectins were used extensively for blood-typing because of their exquisite specificities (the word lectin comes from the Latin word meaning to choose – lego, legere, lexi, lectum for you classicists!)

Although I have always been rubbish at biochemistry, the immunology of cancer started teaching me a bit about the arcane world of what is now called glycomics – the study of sugars in living tissues, and it’s actually nothing like as difficult as you might think. Basically, most proteins, lipids and other molecules in the body have short chains of monosaccharides (sugars) attached to them, called glycans. Some molecules also have long chains of sugars with short protein side-chains attached to them, and there are also glycans attached to other glycans. So we have glycoproteins, glycolipids, proteoglycans and glycosaminoglycans, together making up what chemists call the family of glycoconjugates. Many common proteins in the body are in fact glycoconjugates, and most cells are coated with them.

The nice thing is that the body uses only a very limited repertoire of monosaccharides in most of its glycoconjugates – glucose, galactose (and their respective N-acetyl derivatives), fucose, mannose and sialic acid - and it is the arrangement of these that gives us much of our biochemical individuality, for example the ABO groups (Figure 1) Agglutination of group A red cells by either the appropriate antibody or lectin can be blocked by adding some soluble N-acetyl galactosamine, the terminal sugar of the group A determinant. The sugar is acting as a hapten (the “immunodominant hapten”) and the phenomenon is known as ‘hapten blocking’.

But back to the story. My work in the clinic was bringing me into weekly contact with allergy patients and their intriguing problems, and once my MD thesis was out of the way I largely forgot about cancer and concentrated on allergy.

In my early twenties I myself developed perennial allergic rhinitis, which Geoff Taylor demonstrated was due to dust-mite allergy. He gave me the then-experimental drug cromoglycate to sniff up my nose daily, using a powder insufflator, and that surprisingly cured the rhinitis for the next four decades although the mite allergy is still demonstrable and will give me asthma if I experimentally inhale mite extract.

I remember the symptoms of that rhinitis. I would wake in the morning with the alarm clock, and within about a minute of waking the sneezing would begin – dozens, probably hundreds of explosive sneezes so that by the time I emerged from the shower I would have soaked a whole pack of paper tissues with watery mucus. After about an hour the whole thing was over and done until next morning. While lying in bed waiting for the first sneeze I would become aware of an intense stinging sensation inside the nose, as if some multi-legged creature were clinging onto my poor sensitive mucous membranes with tiny needle-sharp claws. I knew about IgE antibodies and I mused that really it was my antibodies attaching themselves to mite antigens, but it felt as if they were seizing hold of me. When I read about lectins and their ability to attach to mucus membranes I immediately put two and two together and guessed that the allergenic proclivities of dust mites – perhaps allergens in general - must be due to lectins (since confirmed, at least for pollen [1]).

Lectin research gathered pace during the last three decades of the 20th century – my clinical and research lifetime – and we learned of many surprising effects of various lectins on animal tissues including human (Table). The majority of plant lectins are toxic, inflammatory or both; indeed the classic homicidal poison ricin – used to assassinate Gyorgi Markov on a London street 30 years ago, is a lectin.

Table (all references in review article 1)




Local effects on gut after feeding lectin


Kidney bean

Stomach atrophy, stomach emptying delayed

Rat, mouse, pig, rabbit

Wheat, kidney bean, jackbean

Disruption of villi/microvilli


Wheat, kidney bean

Increased intestinal weight Raised intestinal permeability


Kidney bean

Lumping of mucus with patches of naked mucosa Overgrowth by abnormal microbes. Increased faecal weight


Jackbean, wheat

Vascularization of villi with inflammation

Rat, pig

Kidney bean, jackbean, wheat

Crypt cell hyperplasia Increased exfoliation of mucosa. Digestive enzymes disrupted

Mouse, rat

Kidney bean, pea, lentil, soya,

Reduced nutrient uptake

Effects on non-alimentary organs


Wheat, kidney bean

Pancreatic hypertrophy with high polyamine metabolism


Kidney bean

Liver atrophy. Thymic atrophy. Splenic atrophy. Skeletal muscle: raised lipid mobilization, reduced protein and glycogen with hypoinsulinaemia




Effects on whole animal


Kidney bean

Reduced food intake. Negative nitrogen balance Raised blood urea


Kidney bean, jackbean, wheat

Weight loss or impaired growth. Death



Poor growth

Looking down a list of commercially-available lectins 30 years ago, I realised that the majority were from plants that I recognised as common foods – wheat, maize, beans, lentils, peanuts, soya, potato. And wheat (yes, staff of life) tops the list every time. In laboratory parlance the wheat lectin is called WGA (wheat germ agglutinin) although it’s found in other parts of the grain as well. Hey, I thought, these foods are poisonous! No wonder there’s so much food intolerance! (Maybe I’d better repeat that phrase as the idea is so shocking, although well known to farmers and animal husbandmen. These foods are poisonous.) They’re clearly not poisonous enough to make us drop dead, but they are probably accumulating slowly in the body and could well be responsible for many of the food problems I see in the clinic. Bits of knowledge about cancer and allergy suddenly came together into sharp focus.

I persuaded my department to buy a quantity of concanavalin A (conA), the lectin of common jackbeans. Apparently jackbeans are used as animal fodder in America and sometimes for humans, and I knew I had never eaten them (so any response would be uncoloured by any pre-existing immune response). Cautiously, I sniffed a little of the lectin up my right nostril, using the left as control, and to my pained gratification I experienced an indolent rhinitis beginning about an hour later and peaking at about six hours, with pain and discomfort in the rhinopharynx and blood-stained mucous efflux. Just like the initial phase of a cold when you feel ill and feverish but there’s no sneezing. Fascinated, I repeated the experiment monthly, getting rhinitis each time. But after about six doses the reaction became faster, coming on within minutes instead of hours and waning after an hour, and now with violent sneezing and copious clear (not blood-stained) mucus. Just like the mite-allergic rhinitis I remembered from 15 years previously, and just like the second phase of a cold when you start feeling a bit better but sound a lot worse, with sneezing and blocked runny nose. Emboldened, I tried inhaling 10mg of conA into my lungs using an Intal insufflator, and made myself very ill for 24 hours with high fever, prostration and dry cough. I didn’t have the wit to put a stethoscope to my chest or organise an X-ray, but it felt just like the bronchopneumonia I had once caught a few years previously. I wanted to try the experiment again but my wife forbade it!

About 20 years ago I read the first papers describing G0 in rheumatoid disease. IgG antibodies, like so many bioproteins, have short sugar side-chains. When I was learning basic immunology we didn’t know (or care) what those side-sugars were for, but in recent years it has become clear that they are vital to many of the functions of antibodies. The side-chains of healthy IgG molecules terminate with galactose, but there is a truncated form of IgG found in rheumatoid disease that terminates instead in N-acetyl glucosamine, and this aberrant IgG in laboratory jargon is called G0. When I read this paper for the first time I whooped with joy, because suddenly two pieces of hitherto-disparate knowledge made perfect sense, namely: (i) At least 50% of rheumatoid disease in my experience is diet-responsive, and of the various rheumatogenic foods, wheat tops the list every time (confirmed by Dr LM McEwen and Dr J Mansfield). And (ii) wheat contains a famous lectin specific for – guess what – N-acetyl glucosamine, the dominant sugar of G0! Wheat lectins entering the bloodstream from the diet (wheat lectin is particularly resistant to cooking and digestion) would have to bind to the abnormal IgG found there, in which case the IgG would not now be acting as a proper antibody, binding foreign antigens, but would itself be bound by the foreign lectin (a taste of its own medicine). And IgG ‘immune complexes’ play a key role in rheumatoid pathogenesis.

But remember the blood groups? Complexes of wheat lectin and IgG (via its abnormal terminal sugar) are subject, like all receptor-mediated bindings, to the possibility of competitive inhibition by small molecules having the same binding specificity, so if we were to flood the field with free N-acetyl glucosamine, the complexes would dissociate again and the disease would remit. How interesting then, that pharmaceutical-grade “glucosamine”, derived from the chitin of crustacean shells, is so useful for the treatment of rheumatoid disease (in truth it is mainly N-acetyl glucosamine [J Jensenius, personal communication] which fits the lectin hypothesis even better). If glucosamine doesn’t work well, raise the dose to the limit of safety and/or the patient’s budget – remember, there has to be enough to mop up all the ingested lectin and that might be tens of grams.


So the hunt is now on for other chronic diseases that might be caused by dietary lectins, and could be susceptible to the same approach. The ideal candidate disease would be one that clinically responds to dietary elimination of starchy lectin-rich foods (stone-age diet), and/or is associated with abnormal glycosylation of key molecules. Suitable candidate diseases that satisfy one or both criteria (apart from rheumatoid disease) would include Crohn’s disease, IgA nephropathy, Henoch-Schonlein purpura and a potential host of other conditions that we are just beginning to explore. Clinical trials of lectin-blockers are already underway in rheumatoid (Axford’s group, St George’s), and Crohn’s disease (Rhodes’s group, Liverpool). Crohn’s disease has already been successfully treated (albeit in an open trial) with N-acetyl glucosamine by Walker-Smith’s group in London [2]. Work is in progress to determine what kind of elimination and/or blocker might help for IgA nephritis (Smith, Leicester).

To facilitate and focus these efforts Jonathan Brostoff and I, plus a group of like-minded clinicians and glyco-scientists came together together in early ‘07, largely by email but twice so far in the flesh, to coordinate our efforts and discuss progress. Having no name or budget, it was a bit of a nightmare trying to book rooms for meetings at our own expense, so I canvassed the BSEM committee to adopt us as one of its special interest groups. This was agreed – subject to wider approval from the membership, which I hereby solicit – and we met at the Institute of Biology in June ’07 as a satellite meeting of the BSEM Summer meeting.

Elimination dieting used to be central in many areas of Medicine but its power and safety has been forgotten by most of the medical world and it is only our Society which carries that torch now. But for some reason the medical world does find lectins interesting (as witness my signed editorials on the topic which the BMJ published, to my pleasant surprise, in 1985 and 1999 [3-4]) and if the theory works out to be true our Society will receive its proper share of the prestige. Indeed if successful this work could bring about a medical breakthrough on a par with the discovery of antibiotics.

And if on the other hand it doesn’t work, the Society won’t have lost much. In return for the potential prestige, the Lectin Group will benefit from the BSEM’s budget, which although slim is a lot fatter than the Group’s and would probably run to renting a room at the IoB a coupla times a year. So it’s up to you, brethren; please submit any views to the BSEM committee.


1)Freed DLJ. Dietary lectins and disease. In Brostoff J, Challacombe SJ, Food Allergy and Intolerance 2nd ed, Saunders, London, 2002, 479-95

2)Salvatore S, Heuschkel R, Tomlin S, Davies SE, Edwards S, Walker-Smith JA, French I, Murch SH (2000). A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease Alimentary Pharmacology & Therapeutics, 14:1567.

3)Freed DLJ (editorial), Lectins. Br Med J 1985, 290: 584-6

4)Freed DLJ (editorial) Do dietary lectins cause disease? Br Med J 1999, 318: 267-8

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