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The endogenous TLR-4 ligands MRP8/14 as biomarkers of inflammation in Familial Mediterranean Fever (FMF)

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Background

The pro-inflammatory Damage Associated Molecular Pattern (DAMP) molecules Myeloid-Related Protein (MRP)-8/14 have been recently identified as ligands and activators of TLR-4. Familial Mediterranean Fever (FMF) is an auto-inflammatory syndrome associated with activation of phagocytic cells and oversecretion of the proinflammatory cytokine IL-1β. Our aim was to evaluate MRP8/14 serum levels in FMF patients during high inflammatory episodes and during successful therapy.

Patients and methods

70 genetically proven FMF patients were followed up longitudinally over a period of 18 months. Serum concentration of MRP-8/14 determined by ELISA and additionally ESR, CRP and SAA as classical inflammation markers were analysed before starting of therapy and during colchicine treatment. As control groups we measured 17 Neonatal-Onset Multisystem Inflammatory Disease (NOMID), and 18 Muckle Wells Syndrome (MWS) patients.

Results

The mean serum levels of MRP8/14 in inflammatory episodes in FMF (343,210 ± 202,210 ng/ml; n = 17) were significantly higher than in NOMID (2,830 ± 580 ng/ml; p < 0.001), or in MWS (3,205 ± 585 ng/ml; p < 0.001). FMF patients treated with colchicine and not exhibiting any attacks during the study period (5,480 ± 1,900 ng/ml; n = 28) had significantly lower MRP8/14 levels than patients treated with colchicine exhibiting complains typical for FMF (34,700 ± 14,580 ng/ml; p < 0.001; n = 20), and also than Homozygous patients never experiencing any clinical signs without colchicine treatment (22,310 ± 10,110 ng/ml; p < 0.05 n = 5).

Conclusion

MRP8/14 as a marker of phagocyte activation is highly oversecreted in patients with FMF. Measurement of MRP8/14-levels in FMF might be a valuable tool to reflect disease activity, response to anti-inflammatory therapy, and even subclinical inflammatory activity.

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., Kallinich, T., Keitzer, R. et al. The endogenous TLR-4 ligands MRP8/14 as biomarkers of inflammation in Familial Mediterranean Fever (FMF). Pediatr Rheumatol 6, P208 (2008) doi:10.1186/1546-0096-6-S1-P208

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Keywords

  • Colchicine
  • Familial Mediterranean Fever
  • Colchicine Treatment
  • Familial Mediterranean Fever Patient
  • Homozygous Patient