June 11, 2009 Serum levels of the pro-inflammatory biomarkers myeloid-related protein (MRP) 8 and 14 are increased to a greater extent in patients with Familial Mediterranean Fever (FMF) during flare than in patients with Neonatal-Onset Multisystem Inflammatory Disease (NOMID) or patients with Muckle Wells Syndrome (MWS), according to the results of a new study presented June 11 at PReS 2009, a joint congress with the 2009 Congress of the European League Against Rheumatism (EULAR) in Copenhagen, Denmark.
Results of the study indicate that measurement of levels of these biomarkers may enable the prediction of: disease activity, response to anti-inflammatory treatment, differentiation of disorders leading to Fever of Unknown Origin and, potentially, detection of subclinical inflammatory activity in children and adolescents with FMF.
Dr Helmut Wittkowski of the University Hospital Muenster, Germany, who led the study said: "The identification of the role of MRP8/14 during high inflammatory episodes, as well as during successful therapy, offers new insight into the complex underlying mechanisms involved in FMF. Tracking levels of MRP 8/14 may prove a marker for disease activity in FMF and may even lead to earlier diagnosis and improved treatment options for this unique patient population."
MRP8/14 are endogenous danger-signals (damage-associated molecular pattern (DAMP) molecules) that play an important role in inflammatory and immunological responses. They have recently been identified as activators of toll like receptor 4 (TLR-4), a molecule that amplifies phagocyte activation (a type of white blood cell, leucocyte), supporting the immune system by neutralising or engulfing bacteria or other invading micro-organisms.
The mean serum levels of MRP8/14 in inflammatory episodes of FMF (343.210±202.210 ng/ml) were found to be 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 (a commonly-used long-term treatment for the condition) and not exhibiting any flares during the study period (5480±1900 ng/ml) had significantly lower MRP8/14 levels than patients treated with colchicine exhibiting complaints typical for FMF (34.700±14.580 ng/ml; p< 0,001), and also than homozygous (having copies of the FMF gene from both parents) patients without symptoms or treatment (22.310±10.110 ng/ml; p< 0,05).
FMF is a hereditary inflammatory disorder that affects groups of people with a genetic lineage originating from around the Mediterranean Sea. First symptoms usually occur before the age of 18 years and are rare in those over the age of 40 years. FMF is characterised by recurrent, painful, inflammatory attacks lasting between 6 and 72 hours, most of which involve fever and can affect serous tissues in different parts of the body including the abdomen, joints and chest.
In the study, serum concentrations of MRP8/14 were analysed in 51 children and adolescents who had a clinical and/or genetic diagnosis of FMF, using a bespoke ELISA (Enzyme Linked Immunosorbent Assay) system. 17 Neonatal-Onset Multisystem Inflammatory Disease (NOMID) patients and 18 Muckle Wells Syndrome (MWS) patients were used as study controls.
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