Presence of HLA-B27 is associated with changes of serum levels of mediators of the Wnt and hedgehog pathway.
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.
Department of Internal Medicine 3, University Clinic of Erlangen-Nuremberg, Erlangen 91054, Germany.
Sarah
S
Aschermann
Department of Internal Medicine 3, University Clinic of Erlangen-Nuremberg, Erlangen 91054, Germany.
Matthias
M
Englbrecht
Department of Ophthalmology, University Clinic of Erlangen-Nuremberg, Erlangen 91054, Germany.
Antonio
A
Bergua
Department of Internal Medicine 5, Haematooncology, University Clinic of Erlangen-Nuremberg, Erlangen 91054, Germany.
Bernd M
BM
Spriewald
Department of Rheumatology, Université Versailles - Saint-Quentin, Ambroise-Paré Hospital, 92104 Boulogne-Billancourt, France.
Rhula
R
Said-Nahal
Department of Rheumatology, Université Versailles - Saint-Quentin, Ambroise-Paré Hospital, 92104 Boulogne-Billancourt, France.
Maxime
M
Breban
Department of Internal Medicine 3, University Clinic of Erlangen-Nuremberg, Erlangen 91054, Germany. Electronic address: georg.schett@uk-erlangen.de.
Georg
G
Schett
Department of Internal Medicine 3, University Clinic of Erlangen-Nuremberg, Erlangen 91054, Germany.
Jürgen
J
Rech
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000097:blood; D024042:Collagen Type I / Q000097:blood*; D005819:Genetic Markers; D015796:HLA-B27 Antigen / Q000097:blood*; D053823:Hedgehog Proteins / Q000097:blood* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D010455:Peptides / Q000097:blood*; D015398:Signal Transduction; D025241:Spondylarthritis / Q000097:blood* / Q000378:metabolism; D014606:Uveitis, Anterior / Q000097:blood* / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; C501126:DKK1 protein, human; D005819:Genetic Markers; D015796:HLA-B27 Antigen; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C422903:SOST protein, human; D051153:Wnt Proteins; C052929:collagen type I trimeric cross-linked peptide
Bone; HLA-B27; Spondyloarthritis