Activation of microvascular pericytes in autoimmune Raynaud's phenomenon and systemic sclerosis

Objective. To determine the temporal and spatial relationship between platelet-derived growth factor beta (PDGF beta) receptors, PDGF-AB/BB, and activated pericytes across the Raynaud's phenomenon (RP) and systemic sclerosis (SSc; scleroderma) disease spectrum. Methods. Monoclonal antibodies against PDGF beta receptors, PDGF-AB/BB, and high molecular weight-melanoma-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 PDGF beta receptor expression, double immunofluorescence-stained sections were analyzed using computer-aided image analysis and confocal microscopy, Results. PDGF beta receptor-expressing cells and HII 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, PDGF beta receptors were predominantly expressed by microvascular pericytes from both autoimmune RP and early scleroderma skin. Conclusion, PDGF beta 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.