AB0188 Activated platelets are increased in circulation of patients with systemic sclerosis and associated with clinical characteristics. (12th June 2018)

• Record Type: Journal Article
• Authors: Yasuoka, H.; Sakata, K.; Yoshimoto, K.; Yamaoka, K.; Kuwana, M.; Takeuchi, T.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 1281
• Page End: 1281
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.6162
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Systemic sclerosis (SSc) is a systemic connective tissue disease characterised by excessive fibrosis, microvascular injury and autoantibody production 1), but mechanisms of disease process are still under investigation. Recent studies focused on the role of circulating blood cells in the pathogenesis, especially lymphocytes 2, 3) or monocytes 4, 5), however other cellular components are not well-examined. Platelets play a significant role in hemostasis physiologically. However, recent studies have revealed that platelets contain various kinds of humoral factors such as cytokines, chemokines and growth factors and can distribute systemically through circulation and contribute to the disease process through activation and release of these factors 6). Objectives: To elucidate the role of platelets in the pathogenesis of SSc, activation status of circulating platelets in patients with SSc and association with clinical characteristics were examined. Methods: Twenty-one patients with SSc who fulfilled 2013 ACR/EULAR classification criteria and 16 healthy controls were involved. Platelets or microparticles (MPs) were defined as vesicles in platelet-rich plasma which is more or less than 1 µm in diameter by forward and side scatter, respectively, and positive staining with anti-CD41 antibody using flow cytometry. Activation status of platelets was examined by the expression of activation markers on platelets such as P-selectin (CD62P) or activated glycoprotein IIb/IIIa (PAC1). Production of microparticles (MPs) is defined as ratio of proportion of MP to that of platelets. Release reaction of platelets was evaluated by release of platelet factor 4 (PF4) in culture supernatant of coculture with skin fibroblasts using enzyme-linked immunosorbent assay (ELISA). Association or correlation between proportion of activated platelets and clinical characteristics or parameters of patients with scleroderma was also examined. Results: As for the characteristics of 21 patients with SSc, male to female ratio was 3: 18, proportion of diffuse cutaneous SSc was 24%, mean age was 63±13 years, and mean disease duration was 16±13 years. In SSc, both proportion of CD62p+or PAC1 +activated platelets (p<0.05, p<0.05, respectively) and production of MP were higher (p<0.05) compared to those in healthy controls. Of these, proportion of CD62p+platelets and MP production were correlated each other (r=0.88, p<0.05). Also, release reaction of platelet was upregulated in platelets from patient with SSc compared to healthy controls (p<0.05). When activation status of platelets was compared to clinical parameters, both proportion of CD62p+activated platelets and MP production were higher in diffuse cutaneous SSc (p<0.05, p<0.05, respectively) and correlated with modified Rodnan skin score (p<0.05, p<0.05, respectively). Conclusions: In SSc, proportion of activated platelets were higher and associated with skin sclerosis, suggesting the involvement in the pathogenesis of SSc. References: [1] Denton CP, et al. Nat Rev Rheumatol. 2013;9(8):451–64. [2] Almeida I, et al. 2015;49(3):347–69. [3] Yoshizaki A. Immunol Lett. 2018. [4] Moleno-Moral A, et al. Ann Rheum Dis. 2018. [5] Masuda A, et al. Arthritis Res Ther. 2013;15:R74. [6] Semple JW, et al. Nat Rev Immunol. 2011;11(4):264–74. Disclosure of Interest: None declared