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Abstract Number: 2189

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

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Session Information

Session 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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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tlr-4-endogenous-ligand-mrp814-levels-in-enthesitis-related-arthritis-era-and-its-association-with-disease-activity-and-tlr-4-expression/

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