Presence of HLA-B27 is associated with changes of serum levels of mediators of the Wnt and hedgehog pathway

BackgroundHLA-B27 is present in 5% of the Caucasian population and is strongly associated with the development of spondyloarthritis (SpA), a disease characterized by inflammation and substantial bone changes. We hypothesized that the presence of HLA-B27 in itself is associated with alterations of key regulatory of bone homeostasis.MethodsSera of 241 individuals were assessed for the serum levels of Wnt pathway regulators, sclerostin and dickkopf (Dkk)-1 as well as Indian hedgehog (IHH) and collagen type I cleavage products (CTX1). Of the 151 HLA-B27+ subjects, 31 had SpA, 30 had anterior uveitis, 30 were healthy individuals and 60 healthy siblings of patients with SpA.ResultsSclerostin levels were significantly (P < 0.001) lower in HLA-B27+ subjects (314 ± 21 pg/mL) compared to HLA-B27 negative controls (mean ± SEM: 492 ± 30 pg/mL), no matter if subjects were either healthy, or affected by SpA or uveitis. Similar results were found for Dkk-1. No differences between the groups with respect to the bone resorption marker CTX1 were found. In contrast, IHH levels were significantly (P < 0.001) higher in the carriers of HLA-B27 than in the negative controls.ConclusionsChanges in key regulators of the Wnt pathway as well as IHH, a molecule regulating endochondral ossification, are found in HLA-B27 carriers, independent if they were healthy or affected by uveitis or SpA.