Common MEFV mutations in Iranian Azeri Turkish patients with Behçet's disease.
ABSTRACT Behçet's disease (BD) is an inflammatory disorder of unknown cause with higher prevalence along the ancient Silk Road. BD shares epidemiological and clinical features with familial Mediterranean fever (FMF). Moreover, association of BD and certain MEFV gene mutations has been described in recent decades. We studied the role of MEFV mutations in Iranian Azeri Turkish patients with BD.
Fifty-three BD patients who met the International Study Group criteria for BD were analysed for five common MEFV mutations (M694V, V726A, M680I, M694I, and E148Q) using amplification refractory mutation system and polymerase chain reaction (PCR) restriction-digestion testing methods. A cohort of 200 healthy Azeri Turkish individuals who had been previously genotyped regarding the five common MEFV mutations served as the control group.
Eighteen patients were found to carry a single MEFV mutation and one additional patient was compound heterozygote. There was a statistically significant difference between the patient group and ethnically matched healthy individuals regarding M694V and M680I mutations (p = 0.01 and p = 0.04, respectively). Both BD groups (carriers and non-carriers of MEFV mutations) were similar in their clinical symptoms.
Definite MEFV mutations seem to be a susceptibility factor for BD in our cohort of Iranian Azeri Turkish patients.
Article: Autoinflammatory syndromes and cellular responses to stress: pathophysiology, diagnosis and new treatment perspectives.[show abstract] [hide abstract]
ABSTRACT: The term 'autoinflammatory disease' was first proposed in 1999 to encompass some of the distinct clinicopathologic features of a group of monogenic conditions, characterised by recurrent episodes of inflammation, without high-titre autoantibodies or antigen-specific T cells. It was subsequently observed that several of these conditions were caused by mutations in proteins involved in the innate immune response, including, among others, components of the NLRP3 inflammasome, cytokine receptors (tumour necrosis factor receptor 1 (TNFR1)) and receptor antagonists (interleukin 1 receptor antagonist (IL-1RA)). More recently, additional mechanisms linking innate immune-mediated inflammation with a variety of cellular processes, including protein misfolding, oxidative stress and mitochondrial dysfunction, have been recognised to play a role in the pathogenesis of some monogenic autoinflammatory conditions, and also in more common diseases such as type 2 diabetes (T2D), previously perceived as a metabolic disorder, but reclassified as a chronic inflammatory condition. NLRP3 inflammasome activation is induced by islet amyloid polypeptides (IAPPs) in T2D and this condition may, in future, be more commonly treated with targeted anti-cytokine therapies. Caspase 1 activation and release of IL-1β/IL-1 family members is central to the pathogenesis of many autoinflammatory syndromes, as evidenced by the effectiveness of anti-IL-1 biologics in treating these disorders. However, many patients continue to experience symptoms of chronic inflammation, and it will be necessary to translate discoveries on the immunopathology of these conditions into more effective therapies. For example, in tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), the pathogenesis may vary with each mutation and therefore future approaches to treatment of individual patients will require a more tailored approach based on genetic and functional studies.Best practice & research. Clinical rheumatology 08/2012; 26(4):505-33. · 2.90 Impact Factor