TLR 4 Endogenous Ligand MRP8/14 Levels in Enthesitis Related Arthritis (ERA) and Its Association With Disease Activity and TLR 4 Expression

Amita Aggarwal¹, Mujeeb Rahman¹, Arpita Myles², Priyanka Gaur² and Ramnath Misra¹, ¹Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, ²Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Biomarkers, Inflammation, innate immunity and toll-like receptors

Session Information

Title: Pediatric Rheumatology - Pathogenesis and Genetics

Session Type: Abstract Submissions (ACR)

Background/Purpose: Enthesitis related arthritis (ERA) is an inflammatory disease of childhood that lacks autoreactive T and B cells. We have previously shown that surface expressed Toll Like receptors (TLRs) are over-expressed in ERA. Myeloid related proteins (MRP)8/14 are calcium binding proteins that act as an endogenous ligand of TLR-4. MRP8/14 levels are elevated in patients with systemic onset arthritis. Thus we studied its role in ERA.

Methods: The study enrolled patients with ERA (fulfilling ILAR criteria) less than 18 years of age. Plasma and synovial fluid levels of MRP8/14 were measured by ELISA and TLR-4 expression on peripheral blood and synovial fluid monocytes was measured by 2 color flow-cytometry. Control plasma samples were collected from 48 blood bank donors. Follow up samples were obtained from 26 patients after 3-4 months of first sample collection

Results: Among 69 patients 67 were males. Mean age was 15.2±2.7 years, disease duration was 5±3 years. Median plasma levels of MRP8/14 were higher in patients than controls (10862.31,4426.13 ng/ml; p<0.0001) was higher in those with active disease (11669.54, 4421.76 ng/ml, p<0.0001.

Patients with follow up were not different from other patients with respect to duration of disease and treatment received. Plasma MRP8/14 levels reduced on follow up after 3 months only in patients who responded to treatment (10862.31, 3784.41ng/ml, p=0.012). MRP8/14 levels negatively correlated with frequency of CD14+TLR4 positive cells (r=-0.372, p=0.02)

MRP8/14 levels were higher in synovial fluid as compared to plasma (15858.45, 10862.31ng/ml, p=0.024). SFMC showed significantly higher MFI than PBMC (1409.49 ± 890.60 vs. 946.11± 798.92, p=0.005) as well as higher percentage of CD14+TLR-4 positive cells (18.69 ± 4.51 vs. 5.96 ± 3.99, p<0.0001).

Conclusion: MRP814 levels are increased in plasma of ERA patients, are higher in those with active disease and levels decrease in patient who respond to treatment suggesting that it may be a good biomarker during follow up.

Disclosure:

A. Aggarwal,
None;

M. Rahman,
None;

A. Myles,
None;

P. Gaur,
None;

R. Misra,
None.

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