Evidence of Human Leucozyte Antigen-B27 in Healthy Individuals and Patients with Uveitis Is a Risk Factor for Alterations in Bone Metabolism

Sarah Schmidt¹, Stephanie Finzel¹, Jürgen Rech², Matthias Englbrecht¹, Silke Winkler¹, Isabel Schmidt¹, Roula Said-Nahal³, Maxime A. Breban³ and Georg A. Schett¹, ¹Dept of Medicine 3, Rheumatology and Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ²Medizinische Klinik 3, University of Erlangen-Nuremberg, Erlangen, Germany, ³Rheumatology Division, Ambroise Paré Hospital (AP-HP), and Versailles Saint Quentin en Yvelines University, Boulogne-Billancourt, France

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: bone metabolism, human leukocyte antigens (HLA) and spondylarthropathy

Session Information

Title: Spondylarthritis and Psoriatic Arthritis - Pathogenesis, Etiology

Session Type: Abstract Submissions (ACR)

Background/Purpose: To test whether positivity for HLA-B27 per se is associated with changes of biomarkers of the Wnt pathway.

HLA-B27 is strongly associated with the development of spondyloarthritis (SPA), a disease characterized by new bone formation and ankylosis of joints and intervertebral spaces. We have recently shown the role of the two Wnt antagonists, dickkopf 1 (DKK1) and sclerostin in new bone formation in SPA. We therefore hypothesized that HLA-B27 itself may be associated with alterations in expression of DKK1 and sclerostin.

Methods: 31 patients with HLA-B27 positive SPA, 30 patients with HLA-B27 positive uveitis as well as 30 healthy carriers of HLA-B27 were included. Furthermore, we assessed 32 HLA-B27 negative healthy controls comparable for age and gender. We evaluated total DKK1 and sclerostin levels in sera of all individuals by enzyme-linked immunosorbent assays (ELISA). Statistical analysis was done by t-tests using SPSS version 18.0.

Results: Healthy HLA-B27 positive individuals showed significant lower levels of DKK1 compared to negative controls (T (60)= -4.615, p< 0.001). Moreover, DKK1 levels were significant reduced in HLA-B27 positive SPA-patients (T (61)= -3.670, p=0.001) and in HLA-B27 positive uveitis patients (T(60)= -2.445, p=0.017). Lowest levels of DKK1 were found in HLA-B27 positive healthy carriers. Serum levels of sclerostin were significantly lower in HLA-B27 positive SPA-patients compared to HLA-B27 negative individuals (T (61)= -3.130, p=0.003). Additionally, serum levels of sclerostin were distinctly reduced in HLA-B27 positive uveitis patients and in HLA-B27 positive healthy carriers.

Conclusion: HLA-B27 positivity is associated with low levels of DKK1 and sclerostin independent from the presence of clinical symptoms of SPA. Both HLA-B27 healthy carriers as well as HLA-B27 associated uveitis without SPA show lower levels of these two Wnt antagonists than normal HLA-B27 negative controls. These data suggest that alterations in bone metabolism even occur in the absence of clinical SPA and are associated with HLA-B27 carriage.

Disclosure:

S. Schmidt,
None;

S. Finzel,
None;

J. Rech,
None;

M. Englbrecht,
None;

S. Winkler,
None;

I. Schmidt,
None;

R. Said-Nahal,
None;

M. A. Breban,
None;

G. A. Schett,
None.

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