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FRI0515 Neutrophil-Specific S100A12 Phenotype Correlates to Genotype in Familial Mediterranean Fever
  1. F. Gohar1,
  2. B. Orak2,
  3. M. Jeske3,
  4. M. Lieber2,
  5. H. von Bernuth2,
  6. A. Giese4,
  7. E. Weissbarth-Riedel5,
  8. P. Haas6,
  9. F. Dressler7,
  10. D. Holzinger1,
  11. P. Lohse8,
  12. U. Neudorf3,
  13. E. Lainka3,
  14. T. Kallinich2,
  15. D. Foell9,
  16. H. Wittkowski1
  1. 1Department of Paediatric Rheumatology and Immunology, University of Münster, Münster
  2. 2Department of Paediatric Pneumology and Immunology, Charité University Medicine, Berlin
  3. 3Paediatric Rheumatology, University of Duisburg-Essen, Essen
  4. 4Department of Internal Medicine I, Ruhr-University Bochum, Herne
  5. 5Department of Paediatric Rheumatology, University Hospital Hamburg-Eppendorf, Hamburg
  6. 6German Centre for Child and Adolescent Rheumatology, Garmisch-Partenkirchen
  7. 7Centre for Paediatrics and Adolescent Medicine, Hannover Medical School, Hannover
  8. 8Molekulargenetik, Labor Blessing und Partner, Singen
  9. 9Department of Paediatric Rheumatology, University of Münster, Münster, Germany


Background Familial Mediterranean Fever (FMF) is an autoinflammatory disorder associated with MEFV pyrin-encoding gene mutations. S100A12 is a pro-inflammatory “damage associated molecular pattern” molecule and is strongly elevated in active FMF

Objectives To investigate the association between genotype and S100A12 secretion in clinically active, inactive and subclinical disease in vitro and ex vivo.

Methods Serum S100A12 concentration was retrospectively analysed for 125 patients in the German Auto-Inflammatory Diseases Network (AID-Net) Registry according to disease activity and genotype. In vitro, secretion of S100A12, IL-18, IL-1beta and caspase-1 was measured after stimulation of neutrophils from six M694V-positive patients and four healthy controls (HC).

Results S100A12 hypersecretion correlated significantly with clinical disease activity and also with genotype in a “gene-dosing” way, being highest in homozygotes > compound heterozygotes > heterozygotes. M694V-positive heterozygous, compound heterozygous or homozygous patients h had higher S100A12 concentration during inactive and subclinical disease than M694V-negative heterozygous, compound heterozygous or homozygous patients respectively. In vitro, unstimulated neutrophils from M694V-positive patient spontaneously secreted higher S100A12, IL-8 and caspase-1 compared to healthy controls. Colchicine significantly inhibited secretion of S100A12 from stimulated and unstimulated patient neutrophils.

Conclusions FMF phenotype is known to be more severe in patients with M694V mutations. We describe for the first time a biomarker that correlates with clinical disease activity and FMF genotype both ex vivo and in vitro, which has implications for clinical management.


  1. Wittkowski H. et al. Pediatr Rheumatol 2008.

  2. Kallinich T. et al. ARD 2010.

  3. Jeske M et al. Klin Pädiatrie 2013.

Disclosure of Interest None declared

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