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The phagocyte specific protein S100A12 as a novel biomarker in Muckle-Wells-Syndrome before and during therapy with Anakinra and Canakinumab (ACZ885)

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Background

S100A12 is a member of the damage-associated molecular pattern molecules (DAMP) and expressed by activated granulocytes exhibiting its proinflammatory capacity by binding to the Receptor for Advanced Glycation End-products (RAGE). The aim of this study was to evaluate S100A12 in MWS patients before and during therapy with Anakinra (IL1Ra) and Canakinumab (a fully human monoclonal antibody against IL-1β).

Patients and methods

Eight patients (1 male, 7 female) with documented CIAS 1 mutations (5 E311K, 2 T348M, 1 V198M) and active disease were included in this study. After Anakinra treatment therapy was switched to Canakinumab (ACZ885). Muckle-Wells-Syndrome Disease-Activity-Score (MWS-DAS), SAA, CRP, ESR and S100A12 values were recorded one day before (baseline) and during treatment with Anakinra (day 30–120) and Canakinumab (day 8).

Results

MWS-DAS, and all inflammation markers fell significantly from baseline to follow-up in both treatment groups. S100A12 was significantly lower with Canakinumab, than with Anakinra therapy (87 ± 64 ng/ml vs. 145 ± 58; p < 0,05). With Canakinumab, 88% of values were within normal limits within one week of treatment (<120 ng/ml) whereas only 50% of values reached normal range with Anakinra. Correlation between S100A12 and MWS-DAS as well as ESR, CRP and SAA was significant (p < 0,05).

Conclusion

S100A12 is a sensitive marker of inflammation in patients with MWS and may be a valuable parameter to monitor subclinical inflammation. Data indicates that treatment with canakinumab, in contrast to anakinra, normalized S100A12 levels in the majority of patients.

Author information

Correspondence to H Wittkowski.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Wittkowski, H., Kuemmerle-Deschner, J., Gramlich, K. et al. The phagocyte specific protein S100A12 as a novel biomarker in Muckle-Wells-Syndrome before and during therapy with Anakinra and Canakinumab (ACZ885). Pediatr Rheumatol 6, P209 (2008) doi:10.1186/1546-0096-6-S1-P209

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Keywords

  • Normal Limit
  • Specific Protein
  • Molecular Pattern
  • Sensitive Marker
  • Human Monoclonal Antibody