Loading…

Lupus Autoantibodies Recognize the Product of an Alternative Open Reading Frame of SmB/B

An unusual feature of the gene for the spliceosomal protein SmB/B′ is the presence of an unusually long alternative open reading frame (aORF) which could encode 220 amino acids. We cloned and expressed this aORF protein and used immunological assays to determine its antigenicity in patients with sys...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2001-08, Vol.285 (5), p.1206-1212
Main Authors: Kaufman, Kenneth M., Kirby, Monica Y., McClain, Micah T., Harley, John B., James, Judith A.
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:An unusual feature of the gene for the spliceosomal protein SmB/B′ is the presence of an unusually long alternative open reading frame (aORF) which could encode 220 amino acids. We cloned and expressed this aORF protein and used immunological assays to determine its antigenicity in patients with systemic lupus. Sera from 10 of 22 (46%) anti-Sm positive lupus patients showed significant binding to the SmB′ aORF protein by ELISA while neither the normal controls nor anti-Sm negative lupus patient controls showed significant reactivity. Antigenicity of the SmB′ aORF protein was further localized to the C-terminus using a deletion construct. This is the first known example in which the product of an alternative open reading frame acts as an autoantigen in human disease. These results are consistent with the possibility that generation of anti-Sm autoantibodies in a subset of lupus patients is due to abnormal processing and expression of an aORF SmB/B′ message, by an as yet unidentified mechanism.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2001.5302