A New Biomarker for Disease Activity in Large Vessel Vasculitis

By Rula Hajj-ali, MD

Current biomarkers used in giant cell arteritis (GCA) and Takayasu arteritis (TAK) are insufficiently specific for assessing disease activity. To address this critical need, I and my colleagues, including Carol Langford, MD, MHS, Director of the Center for Vasculitis Care and Research at Cleveland Clinic, collaborated with the Vasculitis Clinical Research Consortium to conduct a study to assess whether S100 proteins were associated with disease activity in GCA and TAK. We recently published our results in the Journal of Clinical Rheumatology.

Our approach to assessment

S100 is a calgranulin used as a biomarker in other rheumatic diseases like systemic lupus erythematosus, reactive arthritis, rheumatoid arthritis, oligoarticular and polyarticular juvenile rheumatoid arthritis and ulcerative colitis. Our study was the first to investigate S100 proteins as a biomarker in GCA and TAK.

We obtained serum samples from patients in a longitudinal prospective cohort from several centers internationally, 59 with GCA and 16 with TAK. We used modified American College of Rheumatology criteria for both GCA and TAK to qualify patients and defined active disease as a Birmingham Vasculitis Activity Score (version 1) score > 0 in addition to a physician’s assessment > 0.

We compared average levels of S100A8/S100A9 or S100A12 in inactive and active disease states with a mixed effect model. We used receiver operating characteristic curves with CIs to assess the qualities of disease activity from the developed models using either ESR and CRP or the S100 measurements.

Promising results for GCA

In patients with GCA, mean S100 serum levels were significantly higher during active disease compared with inactive disease (S100A8/S100A9, P = 0.003; S100A12, P = 0.016) and compared with controls (N = 35). In patients with TAK, an increase in active disease in S100A8/S100A9 levels was present but not statistically significant compared with inactive disease. S100A12 levels were not different in active and inactive disease, but all S100 levels were significantly higher than controls, suggesting a potential target for exploration in the disease’s pathogenesis.

S100 proteins levels combined with traditional biomarkers offered the best prediction of disease activity in patients with GCA; S100 levels alone also served as a marker of activity in this disease. Our earlier research showed elevated gene expressions of S100 protein in GCA temporal arteries1 prior to inflammation, thus suggesting an early role for S100 proteins in disease pathogenesis. The current study builds upon these findings and demonstrates the potential utility of S100 proteins in assessing disease activity in GCA, and offers a step toward development of better disease activity measures for large vessel vasculitis.

Dr. Hajj-Ali is Associate Director of the Center for Vasculitis Care and Research in the Department of Rheumatic and Immunologic Diseases.

Reference:

1. Hajj-Ali RH, Lee M, Li J, et al. Distinct patterns of gene expression in temporal artery biopsies associated with pathogenesis of giant cell arteritis. Arthritis Rheum. 2006;54:S756.