Excerpt from Sprue

Synonyms, Key Words, and Related Terms: celiac sprue, gluten-sensitive enteropathy, nontropical sprue, celiac disease, celiac disease, wheat, potbelly

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Background: Sprue (ie, celiac disease) is a permanent intolerance to certain storage proteins (gliadins) found in some cereals (wheat, rye, barley) that occurs in genetically susceptible individuals. Sprue is triggered by an immune-mediated mechanism. In 1888, Samuel Gee first described the classic clinical picture. In the typical presentation of celiac disease in the young child, a combination of a potbelly and thin buttocks are observed, with proximal arm and thigh muscle wasting as a result of nutrient malabsorption.

About 1950, understanding of the disease improved when the Dutch pediatrician W. K. Dicke cleverly observed an association between wheat consumption and incidence of celiac disease. During World War II, wheat was unavailable; therefore, grain products were scarce in Holland. People with sprue had a surprising improvement in their symptoms, which ended when wheat and other grains became available again.

Since then, research has uncovered the pathophysiology of this disease, which has enabled medical understanding and treatment. In 1968, adult nontropical sprue and childhood celiac disease were discovered to be the same affliction.

Sprue can occur at any stage in life; a diagnosis is not unusual in people older than 60 years.

Pathophysiology:

Pathogenesis

Celiac disease is an autoimmune disease, and tissue transglutaminase (tTG) has been discovered to be the autoantigen against which the abnormal immune response is directed. Gluten is the single major environmental factor that triggers celiac disease, which has a narrow and highly specific association with class II haplotypes of human leukocyte antigen (HLA) DR17-DQ2 and, to a lesser extent, DR4-DQ8. However, despite an enormous increase in scientific knowledge in the past few years, the intimate mechanisms leading to the intestinal damage are incompletely understood. Most studies on the pathogenetic mechanisms have been directed toward elucidating the role and function of T cells and related cytokines.

The initial event in the pathogenesis of the celiac lesion is thought to be an abnormal permeability, which allows the entry of gliadin peptides not entirely degraded by the intraluminal and brush border–bound peptidases. Under normal physiologic conditions, the intestinal epithelium bars the passage of macromolecules, such as gluten. Only trace amounts of high-molecular-weight peptides cross this barrier. However, in celiac disease, permeability to macromolecules is increased. This alteration is secondary to a loosening of the intestinal tight junctions, which is possibly a prerequisite for the further development of the immune events to follow.

The epithelial barrier may also be disrupted in the course of a viral infection. This event is believed to be a possible contributing factor to the onset of celiac disease in predisposed individuals.

The early changes induced by exposure to gluten in celiac disease are mediated by the innate branch of immunity, and attention is currently being given to the early events that occur in response to gluten exposure, as they seem pivotal in setting up the subsequent involvement of the adaptive branch of immunity mediated by T cells. The involvement of T cells leads to the celiac disease and its full-blown mucosal changes.

Approximately 95% of all patients express the DQ2 heterodimer, which is encoded by DQA10501/DQB10201, whereas the remaining 5% have DR4 with the DQ8 heterodimer encoded by DQA10301/DQB10302. This strong association implies that the adaptive branch of the immune system (CD4⁺ T lymphocytes in particular) must play a crucial role in the pathogenesis. In fact, DQ2 and DQ8 molecules are located on the surface of antigen-presenting cells (mostly dendritic cells) and bind peptides to be presented to CD4⁺ T lymphocytes. tTG, the major target of autoantibodies in celiac disease, selectivel .....