Serum S100A8/S100A9 and S100A12 As a Marker Of Disease Activity In Giant Cell Arteritis

Jason Springer¹, Dirk Holzinger², Gary S. Hoffman³, Paul A. Monach⁴, Thomas Hamilton⁵, Carol A. Langford⁶, Dirk Foell⁷, David Cuthbertson⁸, Colin O'Rourke⁹, Simon Carette¹⁰, Nader A. Khalidi¹¹, Carol McAlear¹², Christian Pagnoux¹⁰, Philip Seo¹³, Kenneth J. Warrington¹⁴, Steven R. Ytterberg¹⁵, Thomas Vogl¹⁶, Peter A. Merkel¹⁷, Johannes Roth¹⁸ and Rula Hajj-Ali¹⁹, ¹Division of Allergy, Clinical Immunology and Rheumatology, University of Kansas Medical Center, Kansas City, KS, ²Institute of Immunology, University Muenster, Muenster, Germany, ³Center for Vasculitis Care and Research, Cleveland Clinic Foundation, Cleveland, OH, ⁴Rheumatology, Boston University, Boston, MA, ⁵Cleveland Clinic, Cleveland, OH, ⁶Center for Vasculitis Care and Research, Cleveland Clinic, Cleveland, OH, ⁷Department of Pediatric Rheumatology and Immunology, University of Münster, Münster, Germany, ⁸Department of Biostatistics, University of South Florida, Tampa, FL, ⁹Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, ¹⁰Division of Rheumatology, University of Toronto, Toronto, ON, Canada, ¹¹Internal Medicine/Rheumatology, McMaster University, Hamilton, ON, Canada, ¹²University of Pennsylvania, Philadelphia, PA, ¹³Rheumatology Division, Johns Hopkins Vasculitis Center, Johns Hopkins University, Baltimore, MD, ¹⁴Division of Rheumatology, Mayo Clinic, Rochester, MN, ¹⁵Rheumatology Division, Mayo Clinic, Rochester, MN, ¹⁶Institute of Immunology, University of Muenster, Muenster, Germany, ¹⁷Division of Rheumatology, Vasculitis Center, University of Pennsylvania, Philadelphia, PA, ¹⁸Immunology, Institute of Immunology University of Muenster, Muenster, Germany, ¹⁹Cleveland Clinic Foundation, Cleveland, OH

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: biomarkers and giant cell arteritis, Disease Activity

Session Information

Session Title: Vasculitis II

Session Type: Abstract Submissions (ACR)

Background/Purpose: The S100 proteins (S100A8/9 complex and S100A12) are calcium binding proteins expressed during myeloid differentiation. S100 proteins are phagocyte-specific proteins that have been demonstrated to be markers of early recruited phagocytes in various inflammatory disorders. We previously demonstrated that gene expression of the S100A8/A9 and S100A12 are significantly elevated in temporal arteries in patients with giant cell arteritis (GCA), compared to controls. Furthermore, serum concentrations of S100A8/A9 and S100A12 are higher in patients with GCA compared to healthy controls. We aimed to assess the association of S100 proteins in disease activity in GCA and their value in predicting disease activity as compared to standard inflammatory markers (CRP and ESR).

Methods: Fifty-nine patients with GCA were selected from the Vasculitis Clinical Research Consortium Longitudinal Study of GCA. Mean age was 72.3 and 44 (75%) were female. Serum concentrations of S100A8/A9 complex and S100A12 were measured by ELISA in 106 samples at times of active or inactive disease. Data on ESR and CRP values were available for 100 and 94 samples, respectively. Mixed effects model, accounting for repeat measurements, was used to compare S100A8/A9 or S100A12 levels between active and inactive disease. ROC curves were created to compare the utility of CRP and ESR, S100 proteins or a combination of all markers in predicting disease activity.

Results: Estimated mean serum S100A8/9 was significantly higher during active disease (1446 ng/mL) vs. inactive disease (1096 ng/mL), p=0.003. Mean serum S100A12 was also significantly higher during active disease (163 ng/mL) vs. inactive disease (117 ng/mL), p=0.016. The AUC for the combination of S100 proteins and standard markers of inflammation was higher than the AUC for either alone (Figure 1).

Figure 1: Estimated ROC curves for prediction of disease activity in patients with GCA. The grey line is for predictions based on CRP and ESR (AUC = 0.73). The black line is for predictions based on S100A12 and S100A8/9 (AUC = 0.61). The dashed line is the model involving all measurements (AUC = 0.79)

Conclusion:

Serum S100A8/A9 and S100A12 are both significantly elevated during active disease in GCA. The combination of S100 proteins measurements with ESR and CRP enhanced the predictive value of disease activity in GCA.

Disclosure:

J. Springer,
None;

D. Holzinger,
None;

G. S. Hoffman,
None;

P. A. Monach,

Genentech and Biogen IDEC Inc.,

T. Hamilton,
None;

C. A. Langford,

Bristol-Myers Squibb,

Genentech and Biogen IDEC Inc.,

D. Foell,
None;

D. Cuthbertson,
None;

C. O’Rourke,
None;

S. Carette,
None;

N. A. Khalidi,
None;

C. McAlear,
None;

C. Pagnoux,
None;

P. Seo,
None;

K. J. Warrington,
None;

S. R. Ytterberg,
None;

T. Vogl,
None;

P. A. Merkel,
None;

J. Roth,
None;

R. Hajj-Ali,
None.

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