AB0071 SERUM S100A8/A9 (CALPROTECTIN) IN FAMILIAL MEDITERRANEAN FEVER DOES NOT CORRELATE WITH DISEASE ACTIVITY

Background Familial Mediterranean Fever (FMF) is caused by mutations in MEFV. The protein product pyrin is expressed in monocytes, neutrophils and eosinophils. Acute inflammatory attacks are accompanied by a dramatic hepatic acute phase response. S100A8/A9 is damage associated molecular pattern and a TLR4 ligand expressed in neutrophils, monocytes and early infiltrating macrophages. We aimed to investigate S100A8/A9 in 39 patients with FMF, 45 healthy carriers and wild type controls. Objectives To measure S100A8/9 in patients with FMF, carriers and healthy controls. Methods All patients were genotyped. Patients and healthy controls (HC) serum S100A8/A9 levels, cell surface expression on monocytes and neutrophils as well as intracellular peripheral blood mononuclear cells (PBMC) expression were measured by flow cytometry (FACS). CD14 cells were isolated and following overnight incubation with or without LPS, S100A8/A9 was measured in the supernatants by ELISA. Patient and HC monocyte apoptosis was compared. Results Serum levels were measures in 84 samples from 31 patients with homozygous or compound mutations (median 9061ng/ml [range 500-38470], 79 samples from 39 symptomatic patients who were MEFV heterozygotes (median 9394ng/ml [range 1744-38119], 80 samples from 45 individuals with MEFV variants but without clinical features of FMF (median 10939ng/ml [range 2447-u003e40000]. There was no difference in calprotectin concentrations between the different mutations. All the groups described had significantly higher levels than healthy controls (n=16 median 2836ng/ml [range 1058-6175])(p Conclusion Patients with pyrin mutations both with and without clinical disease have greatly elevated serum S100A8/A9 levels without detectable cell surface expression in well-controlled disease with a trend to an increased monocyte intracellular expression. Upon monocyte stimulation with LPS, increased S100A8/A9 is secreted. The exact mechanism by which these patients, especially those with mutations but no clinical disease, demonstrate sustained elevated serum S100A8/A9 remains to be elucidated but does not appear to result in a significant clinical sequelae. Disclosure of Interests Ruth J. Pepper: None declared, Mathew Hutchinson: None declared, S.R. Henderson: None declared, S.K. Todd: None declared, Alan D. Salama: None declared, Philip N Hawkins: None declared, Helen J. Lachmann Grant/research support from: SOBI, Novartis, Consultant for: Novartis, Takeda, Speakers bureau: SOBI. Novartis