Immunocytochemical localization and serologic detection of transforming growth factor beta 1. Association with type I procollagen and inflammatory cell markers in diffuse and limited systemic sclerosis, morphea, and Raynaud's phenomenon.
OBJECTIVE
To determine the presence of transforming growth factor beta 1 (TGF beta 1) and inflammatory cell markers (HLA-DR and Factor XIIIa) and to compare these with the presence of type I procollagen, in clinically uninvolved and involved skin from patients with different subsets of systemic sclerosis (SSc), and to analyze circulating levels of TGF beta 1 in SSc patients.


METHODS
TGF beta 1, HLA-DR, Factor XIIIa, and type I procollagen were detected in skin biopsy sections using a biotin-streptavidin-peroxidase system. Levels of circulating TGF beta 1 were measured using a capture enzyme-linked immunosorbent assay technique.


RESULTS
Patients with active diffuse cutaneous SSc (dcSSc) showed minimal TGF beta 1 but significant type I procollagen staining in involved skin, while the clinically uninvolved skin of these patients showed moderate extracellular and intra-epidermal TGF beta 1 immunoreactivity. Patients with limited cutaneous SSc (lcSSc) showed elevated TGF beta 1 staining in both involved and uninvolved skin, as well as procollagen staining. Significant TGF beta 1 reactivity, HLA-DR and Factor XIIIa immunoreactivity, numerous inflammatory cells, and procollagen staining were seen in specimens from patients with morphea. Sequential biopsies suggested the presence of cytokine activity at the earliest stages of disease, which was not maintained with progression of sclerosis. Among the disease groups studied, elevated levels of circulating TGF beta 1 were seen only in patients with morphea.


CONCLUSIONS
The pattern of TGF beta 1 staining in dermal sections from patients with dcSSc, lcSSc, and morphea suggests that this cytokine is important in the pathogenesis of scleroderma. Furthermore, the presence of TGF beta 1 prior to the onset of fibrosis indicates an early involvement of this growth factor, possibly in the inflammatory stage of the disease.
Higley
H
H
Celtrix Pharmaceuticals, Santa Clara, California.
Persichitte
K
K
Chu
S
S
Waegell
W
W
Vancheeswaran
R
R
Black
C
C
D015415:Biomarkers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D011347:Procollagen / Q000378:metabolism*; D011928:Raynaud Disease / Q000378:metabolism*; D012594:Scleroderma, Localized / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012699:Serology / Q000379:methods; D013194:Staining and Labeling; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism*
D015415:Biomarkers; D011347:Procollagen; D016212:Transforming Growth Factor beta