Objective. To determine the temporal and spatial relationship between platelet-derived growth factor โค (PDGFโค) receptors, PDGF-AB/BB, and activated pericytes across the Raynaud's phenomenon (RP) and systemic sclerosis (SSc; scleroderma) disease spectrum.
Methods. Monoclonal antibodies against PDGFโค receptors, PDGF-AB/BB, and high molecular weightmelanoma-associated antigen (HMW-MAA), a marker for activated pericytes, were used to immunohistochemically analyze serial sections of skin biopsy tissue from patients with RP and from scleroderma patients. To delineate cell-specific PDGFโค receptor expression, double immunofluorescence-stained sections were analyzed using computer-aided image analysis and confocal microscopy.
Results. PDGFโค receptor-expressing cells and HMW-MAA-expressing pericytes were found in biopsy samples from autoimmune RP patients and in both early fibrotic and early nonfibrotic scleroderma skin, but not in normal or primary RP or late-stage scleroderma skin. PDGF-AB/BB was expressed within the epidermis, at the epidermal/dermal junction, and by dermal macrophages. Analysis of juxtaposed serial sections revealed an increased frequency of receptor expression in microvessels from autoimmune RP and early scleroderma skin (P < < < 0.01). Double-labeling studies using confocal microscopy showed that, in vivo, PDGFโค receptors were predominantly expressed by microvascular pericytes from both autoimmune RP and early scleroderma skin.
Conclusion. PDGFโค receptors are expressed by activated microvascular pericytes in patients with autoimmune RP and in early SSc patients, but not in those with primary RP or late-stage scleroderma. These findings suggest that features of autoimmune RP are distinct from those of primary RP, and that microvascular pericytes may be an important link between chronic microvascular damage and fibrosis.