Mononuclear phagocytes represent a heterogeneous population of cells with individual subpopulations exerting different pro- or anti-inflammatory functions. CD163 is a monocyte/macrophage specific marker expressed predominantly on cells which possess strong anti-inflammatory potential. The expression of CD163 is strongly induced by anti-inflammatory mediators such as glucocorticoids and interleukin-10, while being inhibited by pro-inflammatory mediators such as interferon-gamma. CD163-expressing mononuclear phagocytes, as well as soluble CD163, may both take part in downregulating an inflammatory response. It seems, therefore, that CD163 may be an interesting target for therapeutic modulation of the inflammatory response. (Folia Histochemica et Cytobiologica 2011, Vol. 49, No. 3, 365–374) Mononuclear phagocytes represent a heterogeneous population of cells with individual subpopulations exerting different pro- or anti-inflammatory functions. CD163 is a monocyte/macrophage specific marker expressed predominantly on cells which possess strong anti-inflammatory potential. The expression of CD163 is strongly induced by anti-inflammatory mediators such as glucocorticoids and interleukin-10, while being inhibited by pro-inflammatory mediators such as interferon-gamma. CD163-expressing mononuclear phagocytes, as well as soluble CD163, may both take part in downregulating an inflammatory response. It seems, therefore, that CD163 may be an interesting target for therapeutic modulation of the inflammatory response. (Folia Histochemica et Cytobiologica 2011, Vol. 49, No. 3, 365–374)

Objectives. The aim of the study was to investigate serum concentration of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) in SSc patients and to correlate Ang-1 and -2 levels with clinical manifestations. Methods. Serum levels of Ang-1 and -2 were determined by ELISA in 47 SSc patients and 27 healthy controls matched for age and sex. Results. In SSc patients, Ang-1 was significantly lower [mean (s.d.): 21 666.09 (11 516.06) pg/ml], while Ang-2 was significantly increased [2739.60 (1009.25) pg/ml] when compared with the control group [Ang-1: 28607.13 (10 506.93) pg/ml; Ang-2: 1706.28 (556.28) pg/ml, P < 0.01, for both comparisons]. No correlation was observed between Ang-1 and -2 levels. Serum concentrations of Ang-2 correlated with the modified Rodnan skin score (P < 0.01, r = 0.422), the European Scleroderma Study Group (EScSG) disease activity index score (P < 0.001, r = 0.403), ESR (P < 0.05, r = 0.366) and CRP concentration (P < 0.05, r = 0.292), and showed inverse correlation with diffusing capacity for carbon monoxide (DL_CO) (P < 0.01, r = −0.281). Ang-2 was significantly increased in SSc patients with more advanced capillary damage, as indicated by the presence of late capillaroscopic pattern, than in those with less severe microangiopathy (active pattern), and in SSc patients with intermediate/late stage of disease than in SSc subjects with early disease. In multivariate regression analysis, Ang-2 was independently associated with the EScSG activity index [β-coefficient (β = 0.305, P = 0.038], ESR (β = 0.390, P = 0.006) and, inversely, with the presence of digital ulcers (β = −0.426, P = 0.003). Conclusions. Differential expression of Ang-1/Ang-2 might contribute to the pathogenesis of SSc. Ang-2 might be a new biomarker of disease activity in SSc.

Introduction: Systemic sclerosis (SSc) is an autoimmune disease characterized by chronic inflammation, vascular injury and excessive fibrosis. CD163 is a scavenger receptor which affects inflammatory response and may contribute to connective tissue remodelling. It has recently been demonstrated that CD163 can bind and neutralize the TNF-like weak inducer of apoptosis (TWEAK), a multifunctional cytokine which regulates inflammation, angiogenesis and tissue remodelling. We aimed to investigate the relationships between serum levels of soluble CD163 (sCD163) and soluble TWEAK (sTWEAK) in relation to disease manifestations in SSc patients. Methods: This study included 89 patients with SSc who had not received immunosuppressive drugs or steroids for at least 6 months and 48 age- and sex-matched healthy controls (HC) from four European centres. Serum concentrations of sTWEAK and sCD163 were measured using commercially available ELISA kits. Results: The mean serum concentrations of sTWEAK were comparable between SSc patients (mean +/- SD: 270 +/- 171 pg/mL) and HC (294 +/- 147pg/mL, P >0.05). Concentration of sCD163 and sCD163/sTWEAK ratio were significantly greater in SSc patients (984 +/- 420 ng/mL and 4837 +/- 3103, respectively) as compared to HC (823 +/- 331 ng/mL and 3115 +/- 1346 respectively, P mean +2SD of HC) were both associated with a lower risk of digital ulcers in SSc patients (OR, 95%CI: 0.09; 0.01, 0.71, and 0.17; 0.06, 0.51, respectively). Accordingly, patients without digital ulcers had a significantly higher sCD163 concentration and sCD163/sTWEAK ratio as compared to SSc patients with digital ulcers (P <0.01 for both) and HC (P <0.05 for both). A high sCD163/sTWEAK ratio, but not high sCD163 levels, was associated with greater skin involvement. Conclusions: The results of our study indicate that CD163-TWEAK interactions might play a role in the pathogenesis of SSc and that CD163 may protect against the development of digital ulcers in SSc. Further studies are required to reveal whether targeting of the CD163-TWEAK pathway might be a potential strategy for treating vascular disease and/or skin fibrosis in SSc.

Objective.: A proliferation-inducing ligand (APRIL), a member of the tumor necrosis factor (TNF) family, plays a crucial role in the survival of peripheral B cells, and may contribute to the pathogenesis of systemic sclerosis (SSc) through upregulation of autoantibody production and maintenance of autoimmune phenomena. We evaluated the capacity of peripheral blood mononuclear cells from patients with SSc (SSc-PBMC) to produce APRIL; and investigated correlations between production of APRIL by SSc-PBMC and clinical and laboratory features of the disease.Methods.: PBMC from 20 patients with SSc and 14 healthy subjects were incubated in fetal calf serum-supplemented RPMI medium. APRIL levels were determined in cell culture supernatants by ELISA.Results.: PBMC from patients with SSc produced significantly more APRIL (961 ± 151 pg/ml/10⁵cells) than control PBMC (798 ± 219 pg/ml/10⁵cells; p < 0.01). In patients with SSc, increased production of APRIL was associated with the presence of diffuse skin involvement, scleroderma lung disease, peripheral vasculopathy, greater capillary damage on capillaroscopy, and presence of anti-topoisomerase I (anti-topo I) antibodies. Multivariate regression analysis revealed anti-topo I antibodies as the only independent predictor of high production of APRIL by PBMC.Conclusion.: Production of APRIL is increased in SSc-PBMC and is associated with the presence of anti-topo I antibodies and more severe disease. Targeting the APRIL pathway might represent a therapeutic possibility for treatment of patients with SSc, in particular those with anti-topo I antibodies.