Soluble Macrophage Biomarkers Indicate Inflammatory Phenotypes in Patients With Knee Osteoarthritis

Abstract

Objective To evaluate the ability of the macrophage markers CD163 and CD14 to predict different osteoarthritis (OA) phenotypes defined by severity of joint inflammation, radiographic features and progression, and joint pain. Methods We evaluated 2 different cohorts totaling 184 patients with radiographic knee OA. These included 25 patients from a cross-sectional imaging study for whom there were data on activated macrophages in the knee joint, and 159 patients (134 with 3-year longitudinal data) from the longitudinal Prediction of Osteoarthritis Progression study. Multivariable linear regression models with generalized estimating equations were used to assess the association of CD163 and CD14 in synovial fluid (SF) and blood with OA phenotypic outcomes. Models were adjusted for age, sex, and body mass index. P values less than or equal to 0.05 were considered significant. Results SF CD14, SF CD163, and serum CD163 were associated with the abundance of activated macrophages in the knee joint capsule and synovium. SF CD14 was positively associated with severity of joint space narrowing and osteophytes in both cohorts. SF and plasma CD14 were positively associated with self-reported knee pain severity in the imaging study. Both SF CD14 and SF CD163 were positively associated with osteophyte progression. Conclusion Soluble macrophage biomarkers reflected the abundance of activated macrophages and appeared to mediate structural progression (CD163 and CD14) and pain (CD14) in OA knees. These data support the central role of inflammation as a determinant of OA severity, progression risk, and clinical symptoms, and they suggest a means of readily identifying a subset of patients with an active inflammatory state and worse prognosis.

Keratoconus: an inflammatory disorder?

“…It has been proposed that although the disorder does not meet the definition of inflammatory, based on the numbers of leukocytes in synovial fluid, the presence of proinflammatory mediators, which perpetuate disease progression, warrants a reconsideration of the definition of inflammation. [167][168][169] However, with regard to keratoconus, several issues are still to be solved: Why is it that many laboratory studies are indicating elevated levels of inflammatory markers in keratoconus, but clinical and histological findings show little evidence of this inflammation, that is, no significant cell infiltration or neovascularization?…”

Synovial fluid pro-inflammatory profile differs according to the characteristics of knee pain

“…Sf IL-18 was associated with knee pain in a symptomatic knee OA cohort of 69 patients (43). A marker of activated macrophages (soluble CD14) in both sf and plasma was associated with self-reported knee pain in 25 patients (47 knees) with knee OA (48). These pro-inflammatory cytokines may also be responsible for increasing sensory neuron excitability that underlies the chronic pain in OA (12).…”

Encapsulation of allogeneic mesenchymal stem cells in alginate extends local presence and therapeutic function

“…This suggests that MSCs can also stimulate endogenous tissue repair, in addition to their ability to differentiate into cells of the mesoderm lineage. The immunomodulatory property of MSCs is very useful when inflammation is a major contributor to the pathophysiology such as OA (Daghestani et al, 2014), rheumatoid arthritis (Komatsu and Takayanagi, 2015) or GvHD (Le Blanc et al, 2004). Immune suppression by MSCs needs to be induced by pro-inflammatory cytokines such as interferon (IFN)γ, tumour necrosis factor (TNF) α, interleukin (IL)-1α or IL-1β (Groh et al, 2005;Le Blanc et al, 2003;Ren et al, 2008).…”

“…In vitro, MSCs can inhibit B cell derived antibody production (Comoli et al, 2008), generation and function of antigen presenting cells (Nauta et al, 2006) or T lymphocyte proliferation and proinflammatory cytokine production (Di Nicola et al, 2002;Krampera et al, 2003). In vivo, MSCs were able to reduce tissue degradation and inflammation in OA (Daghestani et al, 2014), reduce immune activity in autoimmune enteropathy (Parekkadan et al, 2008), prolong heart and skin allograft survival (Bartholomew et al, 2002;Popp et al, 2008) and improve experimental colitis (Gonzalez-Rey et al, 2009).…”