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TLR4 endogenous ligand MRP8/14 level in enthesitis-related arthritis and its association with disease activity and
Mujeeb T Rahman1, Arpita Myles, Priyanka Gaur
1Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India. amita@sgpgi.ac.in or aa.amita@gmail.com.
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.
Insights
Myeloid-related proteins (MRPs) 8/14 are elevated in children with enthesitis-related arthritis (ERA). Higher MRP8/14 levels indicate active disease and decrease with effective treatment, suggesting its potential as a biomarker.
Area of Science:
- Rheumatology
- Immunology
- Pediatrics
Background:
- Enthesitis-related arthritis (ERA) is a childhood inflammatory disease.
- ERA is characterized by overexpression of Toll-like receptors (TLRs).
- Myeloid-related proteins (MRPs) 8/14 are ligands for TLR4 and elevated in systemic-onset arthritis.
Purpose of the Study:
- To investigate the role of MRP8/14 in ERA.
- To assess MRP8/14 levels in ERA patients compared to controls.
- To correlate MRP8/14 levels with disease activity and treatment response.
Main Methods:
- Plasma and synovial fluid (SF) MRP8/14 levels were measured using ELISA.
- TLR4 expression on monocytes was assessed by flow cytometry.
- Control plasma samples were obtained from blood bank donors.
Main Results:
- MRP8/14 levels were significantly higher in ERA patients than controls (P < 0.0001).
- Elevated MRP8/14 levels correlated with active ERA disease (P < 0.0001).
- Plasma MRP8/14 levels decreased in patients responding to treatment (P = 0.012).
Conclusions:
- MRP8/14 levels are increased in ERA patients' plasma.
- Higher MRP8/14 levels are associated with active disease.
- MRP8/14 may serve as a valuable biomarker for monitoring ERA treatment response.
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