Autoantibodies to the Nuclear Sp100 Protein in Primary Biliary Cirrhosis and Associated Diseases: Epitope Specificity and Immunoglobulin Class Distribution

Scandinavian Journal of Immunology - Tập 36 Số 4 - Trang 555-564 - 1992
Carin Szostecki1, Hans Will1, Hans Netter2,1, H H Guldner1
1Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Hamburg, Germany
2Fox Chase Cancer Center, Philadelphia, PA I9111, USA

Tóm tắt

Sp100, a protein with a dot‐like intranuclear localization in immunofluorescence microscopy, is a major target for patient autoantibodies in primary biliary cirrhosis (PBC) and occasionally in rheumatic disorders. The human Sp 100 cDNA has recently been cloned, and the deduced amino acid sequence was found to contain sequence similarities with an MHC class I domain and several transacting regulatory proteins, including HIV‐1 nef proteins. In this study, recombinant Sp100 fusion proteins were used to differentiate the immunoglobulin isotypes and to map the epitopes involved in the anti‐Sp100 autoimmune response. PBC patients developed IgG as well as IgM and/or IgA class anti‐Sp100 autoantibodies whereas most patients with rheumatic diseases developed IgG class autoantibodies only. For epitope mapping, truncated versions of the Sp100 protein were probed for immunoreactivity in ELISA and immunoblotting. With 55 sera, 17 different reaction patterns were obtained, and at least three non‐overlapping major autoantigenic domains were recognized by the majority of sera. One domain, which contains the sequence similarity with HIV nef proteins, was recognized by all anti‐Sp100 sera and harbours multiple, in part discontinuous, epitopes. These data demonstrate a heterogeneous and patient‐specific anti‐Sp100 autoimmune response which is antigen‐driven and, at least in terms of isotype composition, different in PBC and non‐PBC patients.

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Thông tin xuất bản

Scandinavian Journal of Immunology

Tập 36 Số 4

555-564

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