Expression analysis of caspase1 isoforms in familial mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive inherited disease. The disease is caused by mutation in the MEFV gene, which encodes pyrin. The inflammasome formed by mutant pyrin activates caspase-1 and cause inflammation by triggering the uncontrolled release of Interleukin 1-beta (IL-1b). In this study, the expressions of caspase-1 isoforms in patients during attack and attack-free period were analyzed by quantitative PCR and western blot. Although mRNA expression of alpha isoform in neutrophils was higher in patients with attacks than in attack-free patients, no statistically significant difference was found (p=0.835). However, delta-gamma and epsilon isoforms were found to be statistically significantly decreased in patients with attacks compared attack-free patients (p=0.0047 and p=0.004, respectively). Western blot results showed that only alpha isoform was expressed, but there was no significant difference in expression between patient with attack and attack-free. Although mRNA expression of caspase-1 isoforms (alpha, delta-gamma and epsilon) in peripheral blood mononuclear cells was higher in patients during attack than in attack-free patients, no statistically significant difference was found (p=0.0583, p=0.0712 and p=0.0549, respectively). According to the western blot results, alpha isoform was expressed more in patients with attacks, and beta, delta and gamma isoforms were expressed in attackfree patients. In addition, LPS treatment to THP-1 cells did not cause a difference in the expression of caspase-1 isoforms. Our study is the first to evaluate the expression of caspase-1 isoforms in patients during attack and attack-free periods. Expression of caspase-1 isoforms needs to be evaluated in the larger patient population.