Circulating levels of active transforming growth factor β1 are reduced in diffuse cutaneous systemic sclerosis and correlate inversely with the modified Rodnan skin score

被引:46
作者
Dziadzio, M [1 ]
Smith, RE [1 ]
Abraham, DJ [1 ]
Black, CM [1 ]
Denton, CP [1 ]
机构
[1] UCL, Royal Free & Univ Coll Med Sch, Ctr Rheumatol & Connect Tissue Dis, London, England
关键词
scleroderma; systemic sclerosis; biological markers; severity of illness index; transforming growth factor beta;
D O I
10.1093/rheumatology/kei088
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives. To determine the relationship between clinical features and circulating levels of active transforming growth factor (TGF) beta 1 in the major subsets of systemic sclerosis (SSc). Methods. In a cross-sectional study cases of diffuse cutaneous SSc (dose) (n=27) or limited cutaneous SSc (dose) (n=20) were compared with healthy controls (n=22). Active and total TGF beta 1 was measured in serum and plasma by a high-sensitivity enzyme-linked immunosorbent assay. Results. There were no significant differences between levels of total serum TGF beta 1. However, cases of dcSSc had lower levels of active TGF beta 1 than cases of lcSSc or controls. In addition, more cases of dcSSc (18/27; 66%, P < 0.025) had no detectable active TGF beta 1 than controls (7/22, 32%) or lcSSc (7/20, 35%). In dcSSc, serum active TGF beta 1 levels correlated negatively with skin score and positively with disease duration. Conclusions. Contrary to expectation, levels of active TGF beta 1 are reduced in dcSSc and this correlates with two variables known to associate with disease activity, shorter duration and more extensive skin sclerosis. This suggests that active TGF beta 1 may be sequestered in active involved SSc skin and that serum levels are reduced despite strong evidence implicating TGF beta isoforms in the pathogenesis of fibrosis. Our findings may have implications for systemic TGF beta-trapping therapies in this disease.
引用
收藏
页码:1518 / 1524
页数:7
相关论文
共 40 条
[1]   Making sense of latent TGFβ activation [J].
Annes, JP ;
Munger, JS ;
Rifkin, DB .
JOURNAL OF CELL SCIENCE, 2003, 116 (02) :217-224
[2]   PRELIMINARY CRITERIA FOR THE CLASSIFICATION OF SYSTEMIC-SCLEROSIS (SCLERODERMA) [J].
不详 .
ARTHRITIS AND RHEUMATISM, 1980, 23 (05) :581-590
[3]  
Black CM, 1998, OXFORD TXB RHEUMATOL, V2, P1217
[4]   Mechanisms of disease:: Role of transforming growth factor β in human disease. [J].
Blobe, GC ;
Schiemann, WP ;
Lodish, HF .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342 (18) :1350-1358
[5]  
Choi JJ, 2003, J RHEUMATOL, V30, P1529
[6]  
CLARK R A F, 1987, Journal of Cell Biology, V105, p212A
[7]  
Clements PJ, 2000, ARTHRITIS RHEUM-US, V43, P2445, DOI 10.1002/1529-0131(200011)43:11<2445::AID-ANR11>3.0.CO
[8]  
2-Q
[9]  
CLEMENTS PJ, 1993, J RHEUMATOL, V20, P1892
[10]   Transforming growth factor-β and connective tissue growth factor:: key cytokines in scleroderma pathogenesis [J].
Denton, CP ;
Abraham, DJ .
CURRENT OPINION IN RHEUMATOLOGY, 2001, 13 (06) :505-511