Circulating hydroxy fatty acids in familial Mediterranean fever

Area of Science:

• Biochemistry
• Immunology
• Rheumatology

Background:

• Familial Mediterranean fever (FMF) is characterized by recurrent episodes of fever, serositis, and arthritis.
• These clinical manifestations suggest the involvement of circulating mediators of acute inflammation, particularly neutrophil activation.

Purpose of the Study:

• To investigate the presence and nature of neutrophil-aggregating activities in the sera of FMF patients.
• To identify specific lipid mediators potentially involved in FMF pathogenesis.

Main Methods:

• Quantification of serum neutrophil-aggregating activity using a bioassay.
• Lipid extraction from patient and control sera.
• Chromatographic analysis (including HPLC) and UV spectroscopy to identify lipid structures.
• Gas chromatography/mass spectrometry (GC/MS) for identification of specific hydroxy fatty acids.

Main Results:

• FMF patient sera exhibited significantly higher neutrophil-aggregating activity compared to normal controls.
• Lipid extracts from FMF sera contained compounds with UV absorbance characteristic of conjugated trienes, co-eluting with dihydroxyicosatetraenoic acids.
• Monohydroxy fatty acids, including 5-hydroxyicosatetraenoic acid and hydroxyoctadecadienoic acids, were identified in FMF sera but not in controls or patients with other inflammatory conditions.

Conclusions:

• Circulating mono- and dihydroxy fatty acids are present in FMF patients.
• These findings suggest a potential role for defects in the metabolism or clearance of these hydroxy fatty acids in the pathogenesis of FMF.