**5. Microparticles as an Indicator of Disease Activity**

Microparticles have been attracting increasing attention as potential indicators of eukaryotic cell activation. They could provide valuable information on inflammatory processes in progress, disease activity, and the response to treatment as well as prognosis as a disease assessment indicator.

Hsu et al. demonstrated that release of MPs from platelets activated with collagen decreased considerably after the activity of kinase BTK was inhibited [70]. Reduction of PMPs numbers in other studies with BTK inhibitor in platelet cultures was associated with a decrease in production and the release of inflammatory cytokines IL-6 and IL-8 [71,72]. A considerable increase in the number of platelet, monocyte, and lymphocyte-derived microparticles (CD3, CD19) has been observed in RA patients with high disease activity [52]. Rodrigez-Cario et al. examined the amount of circulating microparticles and their origin in 114 RA patients. The total number of MPs in platelet poor plasma was much higher in individuals with arthritis compared to a group of healthy individuals. The occurrence of different MPs subtypes in this study differed considerably in the RA group and was associated with the clinical course of joint inflammation: The amount of endothelial MPs was associated with the disease duration, the amount of granulocyte MPs was associated with the disease activity as assessed by DAS28, whereas the amount of monocyte-derived MPs was associated with the presence of the rheumatoid factor. The amount of MPs was also associated with the presence of traditional cardiovascular risk factors [59]. The findings of Cloutier et al. could indicate the possibility of using the studies of circulating mpICs to assess RA activity [60]. However, different conclusions were presented by van Eijk et al. based on a study with 24 patients with an early form of RA [51]. The disease activity was assessed based on the ESR, C-reactive protein (CRP) level, and DAS28 score. Moreover, the level of serum amyloid-P (SAP) and the amount of circulating MPs and MPs presenting the C1q complement component was determined in the patients. Nine patients were reassessed after an eight-week intensive treatment according to the COBRA (COmBination therapy in Rheumatoid Arthritis) regimen, which included a combined treatment with methotrexate, sulfasalazine, and prednisolone. As expected, ESR, CRP, and DAS28 improved as a result of the treatment; however, contrary to expectations, neither the amount of circulating MPs, nor MPs with the attached C1q component decreased, which suggests the absence of any connection between the activity of inflammation and MPs release and mpIC production [51]. In a recent paper, Chen demonstrated that inhibition of PMPs formation in an animal model of CIA (collagen-induced arthritis) and reduction of circulating PMPs was associated with a clinical decrease in the disease activity assessed as joint swelling and stiffness [84].
