Serum levels of Wnt-3a are elevated in AS and associated with increased BASMI and mSASSS, independent of age, indicating that Wnt-3a could be a biomarker for the osteoproliferative process.

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Summary We explored relations between serum hepatocyte growth factor (HGF), disease activity, osteoproliferation, and bone mineral density (BMD) in ankylosing spondylitis (AS), in comparison with healthy controls. HGF was increased especially in male AS patients and smokers and associated with both lower BMD and more chronic radiographic changes in the spine. Introduction Ankylosing spondylitis (AS) is characterized by both osteoproliferation and increased bone loss. Biomarkers are requested to predict the processes. The aims of this study were to compare serum levels of hepatocyte growth factor (HGF), matrix metalloproteinase-3 (MMP-3), and vascular endothelial growth factor (VEGF) in AS patients with healthy controls (HC) and to explore the associations with disease activity, osteoproliferation, and bone mineral density (BMD). Methods Serum from AS patients (modified NY-criteria) and HC was analyzed for HGF, MMP-3, and VEGF with ELISA. Disease activity parameters were collected. Osteoproliferation was assessed with modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and BMD was measured in femoral neck. Results Totally, 204 AS patients and 80 sex and age matched HC were included. Serum HGF was higher in the AS patients compared with the HC, whereas serum MMP-3 and VEGF were not. Serum HGF was also higher in smokers and in the male AS patients positively correlated with age, BASMI, and mSASSS, and negatively correlated with BMD. The biomarkers were all positively associated with ESR, CRP, and WBC. In multiple linear regression analysis serum HGF remained associated with higher mSASSS and lower BMD, after adjusting for age, sex, CRP, smoking, and body mass index. Conclusions Serum HGF was increased in male AS patients and associated with higher mSASSS and lower BMD. In addition, serum HGF was positively associated with risk factors for osteoproliferation such as age, CRP and smoking. HGF could be a potential biomarker of importance for the bone metabolism in AS. Trial registration NCT00858819.

In this study we show that human dendritic cells (DC), productively infected with herpes simplex virus type 2 (HSV-2), activate CD8+ T cells that suppress antigen-specific and alloreactive CD4+ T cell expansion. Addition of CD8+ T cells to cultures of DC and CD4+ T cells blocked CD4+ T-cell proliferation in response to HSV-2-infected but not to uninfected DC. The effect was independent of prior HSV exposure or cognate MHC class I-restricted CD8-DC recognition as it was induced in CD8+ T cells from HSV-2-seronegative individuals and in mixed lymphocyte reactions using allogeneic DC. Both CD8+ CD25+ and CD8+ CD25- cells were shown to have suppressive capacities. The blood-derived CD25+ CD8+ T cells did not express Foxp3 mRNA but had a bona fide antiproliferative capacity in response to both uninfected and HSV-2-infected DC, whereas the CD25-CD8+ T cells were selectively activated to become antiproliferative by HSV-2-infected DC. These data imply that HSV infection of DC could modulate the immune response by activating CD8+ T cells.