TLR4 endogenous ligand MRP8/14 level in enthesitis-related arthritis and its association with disease activity and TLR4 expression.
OBJECTIVE
Enthesitis-related arthritis (ERA) is an inflammatory disease of childhood that lacks autoantibodies. Overexpression of surface-expressed Toll-like receptors (TLRs) has been found in ERA. Myeloid-related proteins (MRPs) 8 and 14 are calcium binding proteins that act as an endogenous ligand of TLR4. MRP8/14 levels are elevated in patients with systemic-onset arthritis. Thus we studied the role of MRP8/14 in ERA.


METHODS
The study enrolled patients with ERA. Plasma and SF levels of MRP8/14 were measured by ELISA and TLR4 expression on peripheral blood and SF monocytes was measured by two-colour flow cytometry. Control plasma samples were collected from 48 blood bank donors.


RESULTS
Of the 69 patients, 67 were male, with a mean age of 15.2 (s.d. 2.7) years and a disease duration of 5 (s.d. 3) years. Median plasma levels of MRP8/14 were higher in patients (10 862.3 ng/ml) than controls (4426.1 ng/ml, P < 0.0001). Patients with active disease (11 669.5 ng/ml) had higher levels as compared with inactive disease (4421.8 ng/ml, P < 0.0001). Plasma MRP8/14 levels decreased on follow-up after 3 months only in patients who responded to treatment (P = 0.012). MRP8/14 levels were negatively correlated with the frequency of CD14(+)TLR4(+) cells (r = -0.372, P = 0.02). MRP8/14 levels were higher in SF as compared with plasma (15 858.45 ng/ml, P = 0.024). The frequency of CD14(+)TLR4(+) cells was higher in SF as compared with peripheral blood.


CONCLUSION
MRP8/14 levels are increased in the plasma of ERA patients and are higher in those with active disease and the levels decrease in patients who respond to treatment, suggesting that it may be a good biomarker during follow-up.
['Rahman|Mujeeb T|MT|', 'Myles|Arpita|A|', 'Gaur|Priyanka|P|', 'Misra|Ramnath|R|', 'Aggarwal|Amita|A|']
D000293:Adolescent D000894:Anti-Inflammatory Agents, Non-Steroidal D001171:Arthritis, Juvenile D015415:Biomarkers D040501:Calgranulin A D040502:Calgranulin B D016022:Case-Control Studies D005260:Female D006801:Humans D008024:Ligands D018950:Lipopolysaccharide Receptors D008297:Male D009000:Monocytes D012720:Severity of Illness Index D051197:Toll-Like Receptor 4
calcium binding proteins innate immune response juvenile idiopathic arthritis juvenile spondyloarthritis