The Biochemical Basis of Celiac Disease

Abstract

Cereal Chem. 85(1):1-13Celiac disease (CD) is an inflammatory disorder of the upper small intestine triggered by the ingestion of wheat, rye, barley, and possibly oat products. The clinical feature of CD is characterized by a flat intestinal mucosa with the absence of normal villi, resulting in a generalized malabsorption of nutrients. The prevalence of CD among Caucasians is now thought to be in a range of 1:100-300. There is a strong genetic association with human leukocyte antigens (HLA-)DQ2 and DQ8 and currently unknown non-HLA genes. During the last decade, intense biochemical studies have contributed to substantial progress in understanding the general principles that determine the pathogenesis of CD. The precipitating factors of toxic cereals are the storage proteins, termed gluten in the field of CD (gliadins and glutenins of wheat, secalins of rye, and hordeins of barley). There is still disagreement about the toxicity of oat avenins. The structural features unique to all CD toxic proteins are sequence domains rich in Gln and Pro. The high Pro content renders these proteins resistant to complete proteolytic digestion by gastrointestinal enzymes. Consequently, large Pro-and Gln-rich peptides are cumulated in the small intestine and reach the subepithelial lymphatic tissue. Depending on the amino acid sequences, these peptides can induce two different immune responses. The rapid innate response is characterized by the secretion of the cytokine interleukin-15 and the massive increase of intraepithelial lymphocytes. The slower adaptive response includes the binding of gluten peptides (native or partially deamidated by tissue transglutaminase) to HLA-DQ2 or -DQ8 of antigen presenting cells and the subsequent stimulation of T-cells accompanied by the release of proinflammatory cytokines such as interferon-γ and the activation of matrix metalloproteinases. Both immune responses result in mucosal destruction and epithelial apoptosis. Additionally, stimulated T-cells activate B-cells that produce serum IgA and IgG antibodies against gluten proteins (antigen) and tissue transglutaminase (autoantigen). These antibodies can be used for noninvasive screening tests to diagnose CD. The current essential therapy of CD is a strict lifelong adherence to gluten-free diet. Dietetic gluten-free foods produced for CD patients underlie the regulations of the Codex Alimentarius Standard for Gluten-Free Foods. The "Draft Revised Codex Standard" edited in March 2006 proposes a maximum level of 20 mg of gluten/kg for naturally gluten-free foods (e.g., based on rice or corn flour) and 200 mg/kg for foods rendered gluten-free (e.g., wheat starch). Numerous analytical methods for gluten determination have been developed, mostly based on immunochemical assays, mass spectrometry, or polymerase chain reaction. So far, only two enzyme-linked immunosorbent assays have been successfully ring-tested and are commercially available. During the last decade, future strategies for prevention and treatment of CD have been proposed. They are based...

Duodenal-Mucosal Bacteria Associated with Celiac Disease in Children

“…In addition, a new subset of T cells, termed Th17 cells, was shown to contribute to CD pathogenesis by producing proinflammatory cytokines (such as interleukin-17 , IFN-␥, and IL-21), although these cells can also produce mucosa-protective and regulatory factors (IL-22 and transforming growth factor ␤) (3,4). Some gluten peptides that are not recognized by T cells can induce tissue damage by activating components of innate immunity; thus, peptide p31-43/49 activates the production of IL-15 and natural killer cell receptor-mediated cytotoxicity by intraepithelial lymphocytes, contributing to tissue injury (5)(6)(7). Improvement of the pathological lesions occurring in the intestinal mucosa of sensitive individuals is usually observed after gluten withdrawal from the diet; however, compliance with this dietary recommendation is complex, and other alternative strategies are being investigated (8).…”

Null Alleles in Gliadin Coding Loci and Wheat Allergenic Properties

“…Human IgE class antibodies present in pooled sera of five patients allergic to wheat proteins were used for immunodetection. Such a technique is often applied in the research on wheat allergenicity [20]. Immunological datas evidenced a decrease in OD values for all of the analyzed GDLs as compared with CLs.…”

Effect of Lineage-Specific Metabolic Traits of Lactobacillus reuteri on Sourdough Microbial Ecology

“…Arginine and glutamine conversions partially compensate for the lack of glutamate decarboxylation (15,36,37); glutamate decarboxylase-positive rodent-lineage strains of L. reuteri thus have only a modest advantage over other strains (12; this study). The difference in competitiveness between L. reuteri 100-23 and 100-23⌬gadB was greater in wheat sourdoughs than in sorghum sourdoughs, possibly reflecting the higher content of glutamine plus glutamate in wheat proteins (31% [37]) than in sorghum proteins (19% [38]). L. reuteri 100-23 expressed gadB at the stationary stage but not at the exponential stage of growth (15); accordingly, L. reuteri 100-23 and 100-23⌬gadB were equally competitive in sourdoughs maintained by 12-h fermentation cycles.…”