AUTOANTIGENIC EPITOPES ON DNA TOPOISOMERASE-I - CLINICAL AND IMMUNOGENETIC ASSOCIATIONS IN SYSTEMIC-SCLEROSIS

被引:39
作者
KUWANA, M [1 ]
KABURAKI, J [1 ]
MIMORI, T [1 ]
TOJO, T [1 ]
HOMMA, M [1 ]
机构
[1] KEIO UNIV, SCH MED, DEPT INTERNAL MED, TOKYO 108, JAPAN
来源
ARTHRITIS AND RHEUMATISM | 1993年 / 36卷 / 10期
关键词
D O I
10.1002/art.1780361013
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To elucidate the clinical and immunogenetic associations with reactivity to autoantigenic epitopes on DNA topoisomerase I (topo I) recognized by sera from patients with systemic sclerosis (SSc). Methods. Autoantigenic epitopes on topo I were identified by screening an epitope library constructed from topo I complementary DNA restriction fragments using autoimmune anti-topo I-positive sera as a probe. Epitope reactivities of sera from 43 anti-topo I-positive SSc patients were surveyed by immunoblotting, and associations with clinical symptoms and HLA-DR types were examined. Results. Four different epitope regions were identified on the topo I molecule. Immunoreactivity to the region encompassing amino acid residues 658-700, termed ER4, was found to be associated with diffuse cutaneous SSc, progressive pulmonary interstitial fibrosis, and poor prognosis for 15-year survival. SSc patients with ER4 reactivity frequently displayed the DR2/DRw52 phenotype. Conclusion. Molecular analysis of precise antigenic epitopes on topo I is helpful in classifying clinical subsets of SSc.
引用
收藏
页码:1406 / 1413
页数:8
相关论文
共 35 条
[1]  
AIZAWA M, 1986, HLA ASIA OCEANIA 198
[2]  
[Anonymous], 1979, AM REV RESPIR DIS, V119, P831
[3]   PRELIMINARY CRITERIA FOR THE CLASSIFICATION OF SYSTEMIC-SCLEROSIS (SCLERODERMA) [J].
不详 .
ARTHRITIS AND RHEUMATISM, 1980, 23 (05) :581-590
[4]  
BALDWIN ED, 1948, MEDICINE, V27, P243
[5]   IMMUNOGENETIC PREDICTION OF PULMONARY FIBROSIS IN SYSTEMIC-SCLEROSIS [J].
BRIGGS, DC ;
VAUGHAN, RW ;
WELSH, KI ;
MYERS, A ;
DUBOIS, RM ;
BLACK, CM .
LANCET, 1991, 338 (8768) :661-662
[6]   SEROLOGICAL MARKERS IN PROGRESSIVE SYSTEMIC-SCLEROSIS - CLINICAL CORRELATIONS [J].
CATOGGIO, LJ ;
BERNSTEIN, RM ;
BLACK, CM ;
HUGHES, GRV ;
MADDISON, PJ .
ANNALS OF THE RHEUMATIC DISEASES, 1983, 42 (01) :23-27
[7]   CDNA CLONING OF HUMAN DNA TOPOISOMERASE-I - CATALYTIC ACTIVITY OF A 67.7-KDA CARBOXYL-TERMINAL FRAGMENT [J].
DARPA, P ;
MACHLIN, PS ;
RATRIE, H ;
ROTHFIELD, NF ;
CLEVELAND, DW ;
EARNSHAW, WC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (08) :2543-2547
[8]   USE OF MOLECULAR-CLONING METHODS TO MAP THE DISTRIBUTION OF EPITOPES ON TOPOISOMERASE-I (SCL-70) RECOGNIZED BY SERA OF SCLERODERMA PATIENTS [J].
DARPA, P ;
WHITECOOPER, H ;
CLEVELAND, DW ;
ROTHFIELD, NF ;
EARNSHAW, WC .
ARTHRITIS AND RHEUMATISM, 1990, 33 (10) :1501-1511
[9]  
GULDNER HH, 1988, J IMMUNOL, V141, P469
[10]   THE LUPUS AUTOANTIGENS AND THE PATHOGENESIS OF SYSTEMIC LUPUS-ERYTHEMATOSUS [J].
HARDIN, JA .
ARTHRITIS AND RHEUMATISM, 1986, 29 (04) :457-460