L-Ficolin and H-Ficolin as Links Between Upregulated Immune Response and Increased Rate of Apoptosis in Familial Mediterranean Fever

Abstract

Familial Mediterranean fever (FMF) is autoinflammatory disease characterized by self-limited recurrent episodes of fever (attack) and serosal inflammation. Recent findings suggest the involvement of aberrant apoptosis in pathomechanisms of this disorder. FMF is caused by mutations in the gene of pyrin, a protein, which controls inflammation and apoptosis by regulating interleukin-1β (IL-1β) processing and nuclear-factor-κB and pro-caspase-1 activation. L-ficolin and H-ficolin participate in the clearance of apoptotic cells acting as opsonins or by activating the complement lectin pathway. In this study we evaluated blood serum levels of L- and H-ficolins, and IL-β by the enzyme-linked immunosorbent assay and total leukocyte count (TLC) in attack and attack-free FMF patients in comparison to healthy subjects. Correlation between measured parameters was assessed. Data was analyzed by parametric and nonparametric statistics. Elevated H-ficolin level and TLC were detected in patients during attack period, whereas increased levels of L-ficolin and IL-1β were found in both attack and attack free patients with higher values during attack. Positive correlation between H-ficolin and L-ficolin levels in patients and healthy subjects was detected. Our results suggest excess production of L- and H-ficolins and increased apoptosis rate in FMF and indicate that H-ficolin is operating during development of acute autoinflammatory reactions, whereas L-ficolin is operating in both acute and subclinical autoinflammatory responses associated with this disease.