Autoantibodies to the amino-terminal fragment of β-fodrin expressed in glandular epithelial cells in patients with Sjögren's syndrome

M. Kuwana, T. Okano, Y. Ogawa, J. Kaburaki, Y. Kawakami

研究成果: Article査読

30 被引用数 (Scopus)

抄録

Sjögrens's syndrome (SS) is an autoimmune disease characterized by destruction of lacrimal and salivary glands, but the mechanisms underlying the disease process are unclear. By immunoscreening a HepG2 cDNA library with serum from an SS patient we isolated a cDNA encoding amino-terminal 616 aa of β-fodrin, a membrane skeleton protein associated with ion channels and pumps. Serum Ab to the amino-terminal fragment of β-fodrin was frequently detected in SS patients compared with rheumatic disease patients without SS or healthy controls (70 vs 12 or 4%; p < 0.00001). All the anti-β-fodrin-positive sera recognized the amino-terminal fragment with no homology to α-fodrin. Anti-β-fodrin Abs in patients' sera as well as mouse polyclonal sera raised against the amino-terminal β-fodrin fragment did not react with intact β-fodrin, but recognized the 65-kDa amino-terminal fragment generated through cleavage by caspase-3 or granzyme B. When expression of intact and fragmented β-fodrin in lacrimal glands was assessed by immunohistochemistry, the antigenic amino-terminal fragment was distributed diffusely in acinar epithelial cell cytoplasm, whereas the carboxyl-terminal fragment and/or intact β-fodrin were localized in peripheral cytoplasm, especially at the basal membrane, in SS patients. In contrast, intact β-fodrin was detected primarily at the apical membrane of epithelia, and the amino-terminal fragment was scarcely detected in control patients with chronic graft-vs-host disease. These findings suggest that cleavage and altered distribution of β-fodrin in glandular epithelial cells may induce impaired secretory function and perpetuate an autoimmune response to β-fodrin, leading to autoantibody production and glandular destruction in SS.

本文言語English
ページ(範囲)5449-5456
ページ数8
ジャーナルJournal of Immunology
167
9
DOI
出版ステータスPublished - 2001 11月 1

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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