The role of platelets in autoimmunity, vasculopathy, and fibrosis: Implications for systemic sclerosis

Abstract

Introduction: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, autoimmunity, and widespread dermal and visceral fibrosis. This article summarizes the current knowledge about the potential contribution of platelets in the disease process and the rationale of targeting platelets as an adjunct treatment for SSc.

Methods: We performed an electronic search (Medline) using the keywords platelets, systemic sclerosis, autoimmunity, fibrosis, Raynaud, and pulmonary arterial hypertension.

Results: The link that connects vasculopathy, autoimmunity, and fibrosis in SSc remains obscure. Experimental data suggest that platelets are not solely cell fragments regulating hemostasis but they have a pleiotropic role in several biologic processes including immune regulation, vasculopathy, fibrosis, and all key features of SSc. Platelets interplay with the impaired endothelium, can interact with immune cells, and they are storages of bioactive molecules involved in tissue injury and remodeling. The potential role of platelets in the pathogenesis of SSc is further supported by experimental data in animal models of SSc. Platelet-derived serotonin represents a novel target in SSc and serotonin blockade is currently being tested in clinical trials.

Conclusion: Platelets may be actively involved in the pathogenesis of SSc by activating immune responses and facilitating the fibrotic process. However, definite conclusions cannot be drawn until more data from both basic and clinical research are available.

Keywords: Autoimmunity; Fibrosis; Platelets; Scleroderma; Systemic sclerosis; Vasculopathy.