- [The C282Y mutation may have been positively selected as it mitigates the infertility of celiac disease]?
The poster child of wheat-allergy gastrointestinal tract disease is celiac. The classic symptoms are chronic diarrhea, weight loss, iron deficiency and other evidence of nutrient malabsorption.
Also known as celiac/coeliac sprue and celiac disease, it is an inherited disease in which the intestinal lining is inflamed in response to the ingestion of a protein known as gluten. Treatment of celiac disease involves the avoidance of gluten, which is present in many grains. Inflammation and atrophy of the lining of the small intestine leads to impaired nutrient absorption.
The disease is thought to be an immune reaction to 'glutens' or more specially gliadin, a protein found in the four cereal grains - wheat? (and spelt), rye, oats and barley. A lot of people notice reactions to these foods. One researcher went so far as to say that "...there is increasing evidence that most people with gluten sensitivity have latent celiac disease with such mild manifestations that the diagnosis is never made. " About 4 out of 5 people with celiac disease have antibodies to gliandin in their blood. Surprisingly, it has also been found that half the patients with 'gastrointestinal disorders, in general' had raised antibodies to gliadin as well.
In contrast with having too much of that antibody, it is ten times more common in celiac patients to have a lack of IgA? (the protective antibody in mucus) than in the general population. There is a strong association between being a non-secretor? and having overt celiac disease, non secretors being about 200% more likely to have celiac than secretors (1). This would make sense, since it has been noted for over 20 years that Non-secretors had lower levels of IgA than secretors. Though more recent articles have failed to confirm this for specific ailments (2), other authors point out that the antibodies that were made by the non-secretors in their studies appeared still appeared to be less effective than those antibodies made by the secretors (3).
There is some evidence that the improvement in celiac among non-secretors may be linked to the health of their [Lewis Blood Group? Lewis a blood type antigen] (Le-a). The Le-a blood group substance in the gut of non-secretors is a large molecule. Evidence suggests that this 'large form' of Le-a is converted by the intestinal cells into a 'small form' which can enter the blood stream and pass through the kidneys.
It has been shown that non-secretor? celiac patients who have not regenerated normal mucosa after treatment have significantly levels of 'small Le-a' in their urine when compared with healthy individuals (4). In the one non-secretor celiac patient who healed, the amount of 'small Le-a' in the urine went back to normal. Another study showed that special cells of the intestines called M cells preferentially display the Le-a antigen?, and probably provide the material for other cells to metabolize in healthy systems (5). M cells are important: They are part of the 'Peyer's Patches' of the gut: sort of 'the tonsils of your intestines.' It is in the Peyer's Patches that you build up immune tolerance to foods, or conversely, intolerance. A striking association is that celiac disease predisposes patients to the eventual development of lymphoma, illustrating the intimacy between the immune system and the gut and how it can be deranged by dietary difficulties.
The 'lectin connection' has been extensively studied in celiac disease, though the results are mixed and inconclusive. I suppose the reader is wondering if type O gets more celiac that the other types, especially since I preach that they should minimize wheat?, a food known to be intimately associated with celiac. While there is one study in the literature (6) I've personally found that celiac seems to effect all types about equally, though perhaps for different reasons. Part of the reason seems to be that gliandin, the perpetrator here, is different from wheat germ lectin, the major everyday problem for type O's. For example, studies have reported no ability to bind gliandin or gluten with N-acetyl glucosamine (NAG) the sugar which so handily binds the wheat germ agglutinin (WGA) lectin (7).
This is not to say that gluten doen't appear to be somewhat lectin-like in its own right: Its just not the wheat germ agglutinin (WGA) lectin. Yet gluten has been shown to bind to carbohydrate rich tissues much like a lectin, and to a degree, much like a lectin, gluten can even be inhibited by a specific sugar, alpha-D-mannose. Curiously, many intestinal influenza viruses bind to alpha-D-mannose as well. This perhaps explains the wisdom as pointed out by Freed of the traditional naturopathic wisdom in recommending that a patient fast during gastrointestinal 'flus (8). In addition to bugs, the lectin from the plant Snowdrop (Galanthus nivalis), which is being used to genetically alter foods also binds alpha-d-mannose.
Some ideas to help celiac, other than the obvious measure of removing the offending foods from your diet:
ABH Non-secretors? are at an increased risk for development of celiac disease. One study reported that to 48% of patients with celiac disease were reported to be ABH non-secretors. (2) This appears to be especially true for the recessive Lewis (a-b-) phenotype. Evidence suggests an increased prevalence of complications and celiac-associated abnormalities is also found in the non-secreting and negative Lewis celiac patients. (9)
Lewis phenotype, secretor status, and coeliac disease.
Gut 1994 Jun;35(6):769-770 Dickey W, Wylie JD, Collins JS, Porter KG, Watson RG, McLoughlin JC Department of Medicine, Queen's University of Belfast.
Patients who cannot secrete ABO and [Lewis Blood Group]? antigens into body fluids, an ability controlled by a single gene? on chromosome 19, are known to be at increased risk of certain autoimmune diseases associated with human leucocyte antigen (HLA) markers. This study investigated the possibility of an association with coeliac disease using red cell Lewis (Le) blood group phenotype to infer secretor status. Among 73 patients with coeliac disease who had Le a or b antigen, 48% were non-secretors (Le a + b-) compared with 27% of 137 blood donors (p = 0.004: odds ratio 2.49, 95% confidence intervals 1.37 to 4.51) and 26% of 62 medical and nursing staff controls (p = 0.014: odds ratio 2.65, 95% confidence intervals 1.27 to 5.50). Clinical characteristics did not differ between secretors and non-secretors with coeliac disease. Thus, the non-secretor? state is significantly associated with coeliac disease, suggesting that genes on chromosome 19 may directly or indirectly participate in conferring susceptibility.
1. Dickey W, Wylie JD, Collins JS, et al. Lewis phenotype, secretor status, and coeliac disease. Gut 1994 Jun;35(6):769-70
2. Shinebaum R ABO blood group and secretor status in the spondyloarthropathies. FEMS Microbiol Immunol 1989 Jun;1(6-7):389-95
3.Blackwell CC, May SJ, Brettle RP, MacCallum CJ, Weir DM Secretor state and immunoglobulin levels among women with recurrent urinary tract infections. J Clin Lab Immunol 1987 Mar;22(3):133-74.
4.Evans DA, Donohoe WT, Hewitt S, Linaker BD Lea blood group substance degradation in the human alimentary tract and urinary Lea in coeliac disease. Vox Sang 1982;43(4):177-87
5. Giannasca PJ, Giannasca KT, Leichtner AM, Neutra MR Human intestinal M cells display the sialyl Lewis A antigen Infect Immun 1999 Feb;67(2):946-53
6. Langman MJ, et al ABO blood groups, secretor status, and intestinal alkaline phosphatase concentrations in patients with celiac disease. Gastroenterology. 1969 Jul;57(1):19-23.
7. Ruhlmann J, Sinha P, Hansen G, Tauber R, Kottgen E Studies on the aetiology of coeliac disease: no evidence for lectin-like components i n wheat gluten. Biochim Biophys Acta 1993 Jun 19;1181(3):249-56
8.Freed DJ Dietary Lectins in Food Allergy and Intolerance Brostoff and Callacombe Editors Bailliere Tindall Publishers, London
9. Heneghan MA, Kearns M, Goulding J, et al. Secretor status and human leucocyte antigens in coeliac disease. Scand J Gastroenterol 1996 Oct;31(10):973-6