The condition of celiac disease results in a malabsorption syndrome. Symptoms relate to intrinsic factors (genetic, immune) and to environmental factors (virus and gluten interaction) to cause the enteropathy, celiac sprue. In the condition there is:
- Malabsorption of nutrients in that portion of the small intestine (the jejunum) which is damaged
- a characteristic, though not specific, a lesion of the small intestinal mucosa
- prompt clinical improvement following the withdrawal of selected cereal grains from the diet
Dateline for Celiac Sprue
1888 - described clinically by Samuel Gee;
1952 - recognized as being caused by ingestion of wheat proteins;
1954 - histologic damage to intestinal mucosa described by Dicke;
Celiac Sprue as an Immunologic Disease
a genetic, inheritable disease
linked to genetically transmitted histocompatibility cell antigens [HLA DR3-DQ2, DR5/7 DQ2, and DR4-DQ8]
it is common [1 in 2000 to 2500 carry the diagnosis, undiagnosed GSE may be as common as 1 in 200-400]
the disease is characterized by damage to the mucosal lining of the small intestine which is known as villous atrophy
the damage resulting in malabsorption produces malnutrition
may be linked to skin blisters known as dermatitis herpetiformis
The Mucosal Damage of Celiac Sprue:
the actual damage to intestinal mucosa is
- almost certainly mediated by the immune system
- associated with ANTIBODIES to gliadin, reticulin and/or endomysial [smooth muscle] proteins
- the antibodies probably do not directly cause the damage, though they may be signals for cell-mediated immunity
- the cellular immune system [T cells] probably produces the actual enterocyte injury, but only when gluten-typeprolamins are present
Celiac Sprue as a Pathological Response to Dietary Antigens
technically, gluten-sensitive enteropathy is NOT a food allergy
it is NOT an idiosyncratic reaction to food proteins mediated by IgE
it is NOT typified by rapid histamine-type reaction [typified by bronchospasm, urticaria, etc.]
The Nature of the Injury
slow to develop and is insidious
directly related to ingestion of certain grain prolamins, esp. wheat gliadin proteins [proteins found in wheat, barley, rye, oats, etc.]
results in loss of intestinal villi in the upper small intestine, the jejunum, with loss of absorptive function and the development of inflamation
reversible, if injurious protein is excluded from the diet
reversible to completely normal bowel histology and function
The Damaging Proteins
proteins which are especially rich in proline and glutamine [especially, the amino acid sequences which are in the following orders: Pro-Ser-Gln-Gln and Gln-Gln-Gln-Pro]
these sequences or analogues are especially found in wheat gliadins, rye secalins, barley hordeins and in a much lower amount in oat avenins. It is important to note that these sequences are NOT found in the proteins of corn zein and rice oryzenin
Clinical Features at Onset
There is a remarkable variability in age of GSE diagnosis, from the first to the eighth decade. This variability is due both to delays in making the diagnosis after symptoms develop and to variability in the age of symptom onset.
Severity of Disease and Sensitivity to Gluten
Sprue patients demonstrate a great variability in apparent "sensitivity" to gliadins. Some may experience adverse intestinal function promptly after ingestion of minute amounts of gluten; but most experience a delayed and insidious detrimental effect on intesinal absorption after repeated exposure to [often small amounts] of gluten proteins. The severity of malabsorption also varies.
Treatment for Gluten-Sensitive Enteropathy
Strict adherence to the clinical diet, the gluten-free diet, is the essential mainstay of therapy for GSE. In the absence of gliadin-type protein ingestion, persons with GSE are generally perfectly normal and healthy. Some persons with a long history of damage, or with apparent high "sensitivity," may require an immunosuppressive medication such as prednisone.
Complications of Disease and Failure to Treat
Celiac Sprue which has been of long duration or is neglected by non-compliance to the clinical diet, can be complicated by intestinal lymphoma or other gastrointestinal malignancies. There is a much higher incidence of intestinal lymphoma in GSE patients, an incidence which is reduced by strict adherence to the gluten-free diet.
Role of the Food Industry in Celiac Disease
Persons with GSE recognize that grain proteins are very important diet components for most persons, but they wish for--and depend upon--accurate and understandable product labeling. Since there is no clear minimal amount of gliadin-type protein which is reliably harmless, it is also important that small amounts of gliadin NOT be included in foods which are labeled as gluten-free [for example, as excipients or contaminants, such as might be carried over in multipurpose grain processing equipment]. Secondly, the availability of food variety and quality in the "gluten-free" category is also an important wish of individuals with celiac sprue.
Selected Bibliography
Trier, JS, Celiac Sprue, New England Journal of Medicine, 325:1709-1719, 1991.
Marsh, MN, Gluten, Major Histocompatibility Complex and the Small Intestine, Gastroenterology, 102:330-354, 1992.
Maki, M and Collin, P, Coeliac Disease, Lancet 349:1755-1759, 1997.
Sturgess, RP et al, Cereal Chemistry, Molecular Biology and Toxicity in Coeliac Disease, Gut 32:1055-1060, 1991.
Sturgess, RP et al, Wheat Peptide Challenge in Coeliac Disease, Lancet, 343:759-761, 1994.
