Purification of fibroblast-derived celiac disease autoantigen molecules.

Abstract:

:We have recently purified autoantigen polypeptides reacting with celiac disease patient sera IgA from the extracellular noncollagenous matrix compartment of fetal lung tissue. These molecules trigger the production of different tissue antibodies, the so-called antireticulin and antiendomysium antibodies in celiac disease. In the present report, we show that fibroblasts synthesize and secrete celiac disease autoantigen molecules. The secretion product, reactive with IgA from celiac disease patients, is a large-molecular-weight protein aggregate. When the protein complex was treated with 4 M guanidinium hydrochloride and 0.1% SDS, 11 monocomponent polypeptides could be detected by PAGE. Of these, four single polypeptides with molecular weights of 17,000-39,500 and isoelectric points of 5.0-7.0 were observed to react with IgA separated from sera of children with celiac disease. The polypeptide molecules produced by fibroblasts in vitro bound to antireticulin and antiendomysium antibodies but not to antigliadin antibodies. The present observations show that tissue antibodies found to be specifically associated with celiac disease are generated against a synthesis product of fibroblasts, a cell-type known to synthesize a number of biologically active polypeptides. The fibroblast-derived extracellular matrix proteins and the formed autoantibodies may be important in the pathogenesis of gluten-sensitive enteropathy.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Marttinen A,Mäki M

doi

10.1203/00006450-199310000-00007

subject

Has Abstract

pub_date

1993-10-01 00:00:00

pages

420-3

issue

4

eissn

0031-3998

issn

1530-0447

journal_volume

34

pub_type

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