Possible role for a human adenovirus in the pathogenesis of celiac disease.

Abstract

Celiac disease in humans is activated by the dietary ingestion of wheat, rye, triticale, barley, and possibly oats. Gliadins in wheat and similar proteins in the other grains are known to activate disease in susceptible individuals. There is a striking association between celiac disease and HLA-B8, -DR3 and/or -DR7, and -DC3. Nonetheless, less than 0.2% of individuals with those serologic HLA specificities develop celiac disease and disease is not always concordant among monozygotic twins. We propose that additional environmental factors may be important in the pathogenesis of celiac disease. To investigate that possibility, we examined a data bank of protein sequences for other proteins that might share amino acid sequence homologies with A-gliadin, an alpha-gliadin component known to activate celiac disease and whose complete primary amino acid sequence is known. These studies demonstrate that A-gliadin shares a region of amino acid sequence homology with the 54-kD E1b protein of human adenovirus type 12 (Ad12), an adenovirus usually isolated from the intestinal tract. The region spans 12 amino acid residues, includes 8 residue identities and an identical pentapeptide, and is hydrophilic in both proteins. Antibody reactive with the 54-kD Ad12 E1b protein cross-reacts with A-gliadin, a 119 amino acid cyanogen bromide peptide of A-gliadin that spans the region of homology and a synthetic heptapeptide of A-gliadin from within the region of homology. We suggest that an encounter of the immune system with antigenic determinants produced during intestinal viral infection may be important in the pathogenesis of celiac disease.

Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients.

“…First, since there is genetic variability between c~-gliadins (16)(17)(18), these findings do not allow us to definitively exclude that the T cells actually recognize peptides from this region. Second, although diseaserelevant epitopes can be found in the NH2-terminal region of ol-gliadin (39,40), other regions in both cx-gliadin (39,41) and other gliadins have been suggested to be implicated in the disease (38,(42)(43)(44).…”

Asp57-negative HLA DQβ chain and DQA1*0501 allele are essential for the onset of DQw2-positive and DQw2-negative coeliac disease

“…The replacements in these positions, present in both DQw2-positive and -negative CD patients, could therefore be involved in an incorrect presentation of gluten peptides and thus trigger an abnormal immune response towards gluten. The presence ofthese DQ alleles, also in a certain number of healthy subjects, indicates however that a concurrence of other genetic [26] or environmental [27] factors is necessary for the onset of the disease.…”

Molecular mimicry and myasthenia gravis. An autoantigenic site of the acetylcholine receptor alpha-subunit that has biologic activity and reacts immunochemically with herpes simplex virus.

“…Six of 40 patients with MG tested here had autoantibodies to HuAChR a-subunit, residues 160-167. Although the AChR a-subunit's identity as the immunodominant subunit of the receptor has been noted (21)(22)(23)(24), only recently by using synthetic peptides (5)(6)(7)(8)(9) have specific functional domains been identified.…”