Identification of AHNAK as a novel autoantigen in systemic lupus erythematosus

被引:23
作者
Sköldberg, F
Rönnblom, L
Thornemo, M
Lindahl, A
Bird, PI
Rorsman, F
Kämpe, O
Landgren, E
机构
[1] Uppsala Univ, Univ Hosp, Dept Med Sci, S-75185 Uppsala, Sweden
[2] Sahlgrens Univ Hosp, Res Ctr Endocrinol & Metab, Dept Clin Chem & Transfus Med, S-41345 Gothenburg, Sweden
[3] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia
基金
英国医学研究理事会;
关键词
AHNAK; systemic lupus erythematosus; rheumatoid arthritis; autoantibodies; autoimmunity; apoptosis; granzyme B; caspase-3;
D O I
10.1006/bbrc.2002.6534
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To identify candidate autoantigens associated with arthritis, a rat chondrocyte cDNA library was immunoscreened with serum from a patient with rheumatoid arthritis. One isolated cDNA encoded part of AHNAK, a 700-kDa phosphoprotein with DNA binding properties, that appears to be involved in several signal transduction pathways. Immunoreactivity against an in vitro translated human AHNAK fragment was detected in 4.6% (5/109) of patients with rheumatoid arthritis, 29.5% (18161) of patients with systemic lupus erythematosus (SLE), and 1.2% (2/172) of blood donors. Anti-AHNAK antibodies reacted with a recombinant human AHNAK fragment and with native AHNAK from C32 cell lysates. In vitro translated AHNAK fragment could be cleaved by granzyme B and caspase-3. Anti-AHNAK positive SLE patients had a higher frequency of homogeneous antinuclear antibody staining patterns and a lower frequency of recent mucosal ulcerations. This is the first report that AHNAK can be targeted by the immune system in autoimmune disease. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:951 / 958
页数:8
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