Sarah Aschermann1, Matthias Englbrecht1, Antonio Bergua2, Bernd M Spriewald3, Rhula Said-Nahal4, Maxime Breban4, Georg Schett5, Jürgen Rech1. 1. Department of Internal Medicine 3, University Clinic of Erlangen-Nuremberg, Erlangen 91054, Germany. 2. Department of Ophthalmology, University Clinic of Erlangen-Nuremberg, Erlangen 91054, Germany. 3. Department of Internal Medicine 5, Haematooncology, University Clinic of Erlangen-Nuremberg, Erlangen 91054, Germany. 4. Department of Rheumatology, Université Versailles - Saint-Quentin, Ambroise-Paré Hospital, 92104 Boulogne-Billancourt, France. 5. Department of Internal Medicine 3, University Clinic of Erlangen-Nuremberg, Erlangen 91054, Germany. Electronic address: georg.schett@uk-erlangen.de.
Abstract
BACKGROUND: HLA-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. METHODS: Sera 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. RESULTS: Sclerostin levels were significantly (P<0.001) lower in HLA-B27+ subjects (314±21pg/mL) compared to HLA-B27 negative controls (mean±SEM: 492±30pg/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. CONCLUSIONS: Changes 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.
BACKGROUND:HLA-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. METHODS: Sera 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. RESULTS: Sclerostin levels were significantly (P<0.001) lower in HLA-B27+ subjects (314±21pg/mL) compared to HLA-B27 negative controls (mean±SEM: 492±30pg/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. CONCLUSIONS: Changes 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.
Authors: Harjit P Bhattoa; Zoltán Szekanecz; Boglárka Soós; Ágnes Szentpétery; Hennie G Raterman; Willem F Lems Journal: Nat Rev Rheumatol Date: 2022-03-10 Impact factor: 20.543