BACKGROUND: Sera of patients with coeliac disease, containing IgA and IgG antigliadin antibodies (AGA) and various IgA autoantibodies, react with isolated enterocytes. AGA cross react with enterocyte antigens, one of which has been identified as calreticulin. AIMS: To characterise the antigenic structures of gliadin, enterocytes, and calreticulin recognised by AGA from patients with active coeliac disease. METHODS: AGA were isolated from sera of nine patients by affinity chromatography and tested by competitive ELISA using 40 alpha-gliadin synthetic dodecapeptides (A1-F6). RESULTS: Reactivity of gliadin with all purified AGA tested was inhibited by peptide A4 at the N-terminal region; by C2, C3, and D4 at the central region; and by F3 and F4 at the C-terminal region of the gliadin molecule. AGA cross reactivity with enterocytes was inhibited by peptides A4, D1-D4, and F6 and with calreticulin by peptides A4, D3, and D4. As dominant epitopes AGA of coeliac patients recognise similar structures corresponding to peptides A4, D3, D4, and F6 present on gliadin, enterocytes, and calreticulin. Substitution of glutamine in the A4 peptide by glutamic acid caused loss of inhibitory capacity. Shortening of peptide A4 on the N-terminal by three amino acids increased its inhibitory effect. CONCLUSIONS: AGA of patients with coeliac disease react with similar structures on gliadin and potential autoantigens on enterocytes.

Department of Immunology Institute of Microbiology Czech Academy of Sciences Prague

Gut. 1999 Feb;44(2):151-2. doi: 10.1136/gut.44.2.151. PubMed

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Immunol Today. 1992 Dec;13(12):474-6 PubMed

Biochem J. 1992 Aug 1;285 ( Pt 3):681-92 PubMed

Gastroenterology. 1992 Jan;102(1):330-54 PubMed

N Engl J Med. 1991 Dec 12;325(24):1709-19 PubMed

Lancet. 1990 Dec 1;336(8727):1335-8 PubMed

J Pediatr Gastroenterol Nutr. 1991 Feb;12(2):150-8 PubMed

Gut. 1990 May;31(5):497-9 PubMed

Pept Res. 1990 Jul-Aug;3(4):182-93 PubMed

Arch Dis Child. 1990 Aug;65(8):909-11 PubMed

Biochem Int. 1990;21(3):581-91 PubMed

J Immunol Methods. 1986 Jul 11;91(1):65-73 PubMed

Gastroenterology. 1988 Jan;94(1):41-9 PubMed

Cell. 1987 Sep 11;50(6):819-20 PubMed

Lancet. 1971 Sep 25;2(7726):681-2 PubMed

Nature. 1967 Jun 24;214(5095):1302-4 PubMed

Br J Dermatol. 1984 Oct;111(4):395-402 PubMed

J Pediatr. 1984 Dec;105(6):901-5 PubMed

Proc Natl Acad Sci U S A. 1984 Aug;81(15):4712-6 PubMed

Clin Immunol Immunopathol. 1994 Apr;71(1):75-81 PubMed

Hum Immunol. 1994 Apr;39(4):243-52 PubMed

Cell. 1995 Mar 10;80(5):695-705 PubMed

Gut. 1995 Jun;36(6):874-9 PubMed

Biochem Biophys Res Commun. 1995 Apr 17;209(2):597-605 PubMed

Clin Immunol Immunopathol. 1995 Feb;74(2):170-6 PubMed

Lancet. 1994 Mar 26;343(8900):758-61 PubMed

Pediatr Res. 1993 Oct;34(4):420-3 PubMed

Cell Tissue Res. 1977 Jan 12;176(2):167-78 PubMed

Gut. 1993 Feb;34(2):150-1 PubMed

Gut. 1995 Dec;37(6):766-76 PubMed

Clin Immunol Immunopathol. 1996 Jun;79(3):288-93 PubMed

Clin Exp Immunol. 1996 Nov;106(2):344-50 PubMed

Gastroenterology. 1997 Mar;112(3):752-9 PubMed

Nat Med. 1997 Jul;3(7):797-801 PubMed

Gut. 1997 Oct;41(4):565-6 PubMed

Clin Immunol Immunopathol. 1997 Dec;85(3):289-96 PubMed

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