title: Accelerated apoptosis of neutrophils in familial mediterranean Fever.
abstract: The causative mutations for familial Mediterranean fever (FMF) are located in the MEFV gene, which encodes pyrin. Pyrin modulates the susceptibility to apoptosis via its PYD domain, but how the mutated versions of pyrin affect apoptotic processes are poorly understood. Spontaneous and induced rates of systemic neutrophil apoptosis as well as the levels of proteins involved in apoptosis were investigated ex vivo in patients with FMF using flow cytometry and RT-qPCR. The freshly collected neutrophils from the patients in FMF remission displayed a significantly larger number of cells spontaneously entering apoptosis compared to control (6.27 ± 2.14 vs. 1.69 ± 0.18%). This elevated ratio was retained after 24 h incubation of neutrophils in the growth medium (32.4 ± 7.41 vs. 7.65 ± 1.32%). Correspondingly, the mRNA level for caspase-3 was also significantly increased under these conditions. In response to the inducing agents, the neutrophils from FMF patients also displayed significantly elevated apoptotic rates compared to control. The elevated rates, however, can be largely explained by the higher basal ratio of apoptotic cells in the former group. Monitoring of several proteins involved in apoptosis has not revealed any conventional mechanisms contributing to the enhanced apoptotic rate of neutrophils in FMF. Although the exact molecular mechanisms of accelerated neutrophil apoptosis in FMF remain unknown, it may provide a protection against excessive inflammation and tissue damage due to a massive infiltration of neutrophils in the acute period of the disease.
authors.affiliation: Group of Molecular and Cellular Immunology, Institute of Molecular Biology, National Academy of Sciences , Yerevan , Armenia.
authors.forename: Gayane
authors.initials: G
authors.lastname: Manukyan
authors.affiliation: National Veterinary Institute, Technical University of Denmark , Copenhagen , Denmark.
authors.forename: Rustam
authors.initials: R
authors.lastname: Aminov
authors.affiliation: Department of Internal Medicine, Yerevan State Medical University , Yerevan , Armenia.
authors.forename: Gagik
authors.initials: G
authors.lastname: Hakobyan
authors.affiliation: Analytical Laboratory Branch, Scientific Centre of Drug and Medical Technology Expertise JSC , Yerevan , Armenia.
authors.forename: Tigran
authors.initials: T
authors.lastname: Davtyan
keywords: apoptosis; autoinflammation; familial Mediterranean fever; neutrophils; whole blood