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.


CONCLUSIONS
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.
Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India. amita@sgpgi.ac.in or aa.amita@gmail.com.
Mujeeb T
MT
Rahman
Arpita
A
Myles
Priyanka
P
Gaur
Ramnath
R
Misra
Amita
A
Aggarwal
D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D040501:Calgranulin A / Q000378:metabolism*; D040502:Calgranulin B / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D008024:Ligands; D018950:Lipopolysaccharide Receptors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
calcium binding proteins; innate immune response; juvenile idiopathic arthritis; juvenile spondyloarthritis