Neprilysin levels in plasma and synovial fluid of juvenile idiopathic arthritis patients.
OBJECTIVE
Neprilysin (neutral endopeptidase, 3:4:24:11, CD10) (NEP) is a Zn metallopeptidase linked to controlling inflammation through the degradation of neuropeptides involved in neurogenic inflammation of chronic rheumatic diseases. The aim of our study was to evaluate circulating activity and cellular expression of NEP in the plasma of 58 children with juvenile idiopathic arthritis (JIA) and 52 controls. In 20 subjects requiring local steroid injection, NEP was measured in synovial fluid.


METHODS
Plasma and synovial NEP were evaluated using a fluorimetric technique. Neprilysin, expressed as the antigen CD10, was determined on circulating and synovial fluid cells as mean fluorescence intensity (MFI) and as percentage of positive cells by two-color immunofluorescence.


RESULTS
Circulating NEP levels were lower in JIA patients than in controls (42.0+/-16.6 vs 76.5+/-24 pmol/ml per min, P<0.001), while synovial fluid NEP values were higher than circulating levels (241.4+/-86.2 vs 40+/-15.3 pmol/ml per min, P<0.001). In monocytes, the percentage of CD10-positive circulating cells and the MFI in JIA were lower than in controls (11.6+/-5.2% vs 41.4+/-13%, P<0.001 and 18.1+/-7.5 vs 31.2+/-5.4, P<0.05, respectively). On synovial monocytes, the percentage of CD10-positive cells and the MFI were higher than on circulating monocytes (35.2+/-14.6% vs 9.1+/-2.4%, P<0.001 and 66.4+/-5.4 vs 22.8+/-14.7, P<0.001, respectively).


CONCLUSIONS
The downregulation of CD10 expression in monocytes and the reduction in NEP activity may be linked to the enzyme's role in the control of peptides involved in the inflammation. The increased levels of NEP, MFI, and CD10-positive monocytes in synovial fluid, even though in plasma, might reflect a reactive effort to control synovial proliferation.
Simonini
Gabriele
G
Rheumatology Unit, Department of Pediatrics, University of Florence, Via Pico della Mirandola 24, 50132 Florence, Italy. gabriele.simonini@unifi.it
Azzari
Chiara
C
Gelli
Anna Maria Grazia
AM
Giani
Teresa
T
Calabri
Giovanni Battista
GB
Leoncini
Gigliola
G
Del Rosso
Angela
A
Generini
Sergio
S
Cimaz
Rolando
R
Cerinic
Marco Matucci
MM
Falcini
Fernanda
F
D001171:Arthritis, Juvenile / Q000097:blood* / Q000473:pathology; D002452:Cell Count; D002648:Child; D015536:Down-Regulation; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D015260:Neprilysin / Q000097:blood*; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism*
D015260:Neprilysin