Back to Search
Start Over
FRI0515 Neutrophil-Specific S100A12 Phenotype Correlates to Genotype in Familial Mediterranean Fever
- Source :
- Annals of the Rheumatic Diseases. 74:615.1-615
- Publication Year :
- 2015
- Publisher :
- BMJ, 2015.
-
Abstract
- 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. References Wittkowski H. et al. Pediatr Rheumatol 2008. Kallinich T. et al. ARD 2010. Jeske M et al. Klin Padiatrie 2013. Disclosure of Interest None declared
- Subjects :
- business.industry
Immunology
Familial Mediterranean fever
Heterozygote advantage
Gene mutation
Compound heterozygosity
MEFV
medicine.disease
General Biochemistry, Genetics and Molecular Biology
chemistry.chemical_compound
Rheumatology
chemistry
Genotype
Immunology and Allergy
Medicine
Biomarker (medicine)
Colchicine
business
Subjects
Details
- ISSN :
- 14682060 and 00034967
- Volume :
- 74
- Database :
- OpenAIRE
- Journal :
- Annals of the Rheumatic Diseases
- Accession number :
- edsair.doi...........967e4779eda2d083bfcd37666b898e4b