Urine Matrix Metalloproteinase-3 Level as a Biomarker for Monitoring in Familial Mediterranean Fever Attacks

Abstract

Objective: Matrix metalloproteinase-3 (MMP-3) has been implicated in experimental and clinical models of human inflammatory conditions. Increased MMPs levels have been shown in serum and body fluids in inflammatory conditions. Familial Mediterranean Fever (FMF) is an inherited, auto inflammatory disease characterized by recurrent self-limited bouts of fever and localized inflammation. We aimed to investigate whether urine MMP-3 level can serve as a biomarker for monitoring attack in FMF patients in daily practice. Methods:We studied 50 patients diagnosed with FMF according to Tel Hashomer criteria and 32 age-matched healthy controls. We determined all subjects both in attack (FMF-AP) and attack free period (FMF-AFP) groups. Serum and urine samples were obtained within the first 6-24 h of the AP, and 10 days later after the attack (AFP). The serum samples were measured on the same day while urine samples were frozen immediately and stored at -80°C. Results:The mean age at onset was 57.26 ± 33.5 months. The most common symptoms seen during the attacks were: fever (80%) abdominal pain (72%), arthritis (40%). In genotype distribution, homozygous M694V mutation was seen mostly (28%). During AP, urine MMP-3 levels of patients were higher as well as during AFP and controls (2.32 ± 0.51, 0.89 ± 2.29 ng/mL and 1.24 ± 0.17 ng/mL, respectively, p=0.00). In AP, urinary MMP levels were higher in patients with arthritis than others (p<0.05). Urinary MMP-3 levels were also significantly higher in males (2.29 ± 0.45 versus 2.24 ± 0.57, p=0, 00). The patients with M694V allele (n=29) had statistically significant high urine MMP-3 levels than others (2.37 ± 0.56 versus 1.99 ± 0.31, p=0.04, respectively). Also, acute phase reactants were higher in patients with M694V allele without statistically significant difference (p=0. 89, 0.75, 0.86, 0.85, 0.7, respectively). Conclusion:In this study we focused on presence of MMPs in urine and showed inflammation-specific MMP patterns may provide clinicians valuable information in FMF patients.

Ultrasound measurement of femoral cartilage thickness in patients with familial Mediterrean fever and its relation to amyloidosis and other disease characteristics

“…[ 17 ] Similarly, in a study of pediatric patients with FMF, MMP-3, a direct effector of cartilage and synovial damage, was higher in FMF, especially in those with arthritis. [ 18 ] Although abdominal pain and fever are the most common symptoms in FMF, arthritis may develop in approximately 21–77% of patients. [ 19 ] The joint attacks are usually monoarticular, transient, and involve large joints such as the knee, ankle, and hip.…”