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 RAYNAUDS-PHENOMENON

Objective. To determine the presence of transforming growth factor bet a 1 (TGF beta 1) and inflammatory cell markers (HLA-DR and Factor XIII a) and to compare these with the presence of type I procollagen, in cl inically uninvolved and involved skin from patients with different sub sets 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 tec hnique. Results. Patients with active diffuse cutaneous SSc (dcSSc) sh owed 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 immunore activity. Patients with limited cutaneous SSc (IcSSc) showed elevated TGF beta 1 staining in both involved and uninvolved skin, as well as p rocollagen staining. Significant TGF beta 1 reactivity, HLA-DR and Fac tor XIIIa immunoreactivity, numerous inflammatory cells, and procollag en staining were seen in specimens from patients with morphea. Sequent ial biopsies suggested the presence of cytokine activity at the earlie st stages of disease, which was not maintained with progression of scl erosis. Among the disease groups studied, elevated levels of circulati ng TGF beta 1 were seen only in patients with morphea. Conclusion. The pattern of TGF beta 1 staining in dermal sections from patients with dcSSc, IcSSc, 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 th is growth factor, possibly in the inflammatory stage of the disease.