Serum levels of tissue inhibitor of metalloproteinases 2 in patients with systemic sclerosis.
BACKGROUND
The serum tissue inhibitor of metalloproteinases 1 (TIMP-1) level was reported to be a useful indicator of disease activity, especially of lung fibrosis in patients with systemic sclerosis. TIMP-2 is also an important inhibitor of matrix metalloproteinases (MMPs), such as interstitial collagenase, gelatinase, and stromelysin, which control the metabolism of the extracellular matrix. However, serum levels of TIMP-2 in patients with systemic sclerosis (SSc) have not been investigated.


OBJECTIVE
We sought to determine the clinical significance of serum levels of TIMP-2 and MMP-2 in patients with SSc.


METHODS
Serum samples were obtained from 128 patients with SSc (68 with limited cutaneous SSc and 60 with diffuse cutaneous SSc). Twenty-seven serum samples from healthy age- and sex-matched individuals were also examined as controls. The TIMP-2 and MMP-2 levels were determined by means of sandwich enzyme-linked immunosorbent assays.


RESULTS
The serum TIMP-2 levels were elevated in 29 (22.7%) of the 128 patients with SSc and were significantly higher than those of the healthy control subjects. The serum TIMP-2 levels were significantly correlated with the extent of skin sclerosis in the patients with SSc. The incidence of decreased percentage of the diffusing capacity of lung for carbon monoxide (DLCO ) and that of an elevated erythrocyte sedimentation rate were significantly greater in the patients with elevated TIMP-2 levels compared with the patients with normal TIMP-2 levels (P <.05). When these patients were classified into 2 groups by disease activity, TIMP-2 levels were significantly more elevated in the high active group than in those low active group (P <.001). The serum MMP-2 levels of the patients with SSc were not significantly higher than those of the healthy control subjects.


CONCLUSIONS
These findings suggest that the serum TIMP-2 level is a useful marker of the extent of skin sclerosis and disease activity in patients with SSc. The balance of TIMP-2 and MMP-2 may play an important role in patients with SSc. Furthermore, TIMP-2 may be thought to contribute to the development of disease in patients with SSc.
Yazawa
N
N
Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan.
Kikuchi
K
K
Ihn
H
H
Fujimoto
M
M
Kubo
M
M
Tamaki
T
T
Tamaki
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D011653:Pulmonary Diffusing Capacity; D012595:Scleroderma, Systemic / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D012867:Skin / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D014797:Vital Capacity
D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2