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Abstract Number: 317

Myeloid Related Proteins 8 and 14 (MRP 8/14) – Potential Biomarkers of Disease Activity of Arthritis in Children with Trisomy 21

Charlene Foley, Orla Killeen and Emma Jane MacDermott, The National Centre for Paediatric Rheumatology, Dublin, Ireland

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Biomarkers, juvenile arthritis and pediatric rheumatology

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Session Information

Title: Pediatric Rheumatology - Pathogenesis and Genetics

Session Type: Abstract Submissions (ACR)

Background/Purpose

JIA is an umbrella term used to describe a heterogeneous group of diseases.To date no specific markers exist in clinical practice to predict disease activity & outcome. MRP8/14 are calcium-binding proteins secreted by infiltrating phagocytes in synovial inflammation.Studies have shown that their serum concentrations correlate sensitively & specifically with synovial inflammation in JIA. It is believed that they are predictive biomarkers that can indicate subclinical disease activity & identify patients at risk of relapse during times of clinically inactive disease.They have also been shown to identify patients more likely to respond to treatment with Methotrexate.To date there have been no studies looking specifically at their use in Down’s Arthropathy (DA). 

Objectives

To evaluate the use of standard (ESR&CRP) & novel (MRP8/14) inflammatory markers as biomarkers of disease activity in DA & JIA.

Methods

Between May 2013-May 2014 new cases of JIA & DA attending the NCPR had blood drawn to measure their CRP, ESR & MRP 8/14 levels at diagnosis.Corresponding Active Joint Count (AJC) was documented. Paired synovial fluid (SF) samples were taken for analysis from children requiring steroid joint injections as treatment for their arthritis. Serum (Se) & SF concentrations of MRP 8/14 were determined by sandwich ELISA.The reader of laboratory assays was blinded for diagnosis & inflammatory activity.CRP & ESR were measured as part of routine clinical assessment.

Results

32 children (20 JIA,12 DA) had serum samples taken for CRP,ESR & MRP8/14 levels at diagnosis. 14 of these children had paired synovial fluid samples taken.The average AJC was 4 (range 1-11).Table1 highlights accuracy of each measurement as a marker of disease activity.In DA,a significant correlation was detected between AJC & both ESR and MRP 8/14 (SF).Combining results for the DA & JIA cohort,a significant positive correlation was noted between paired samples of MRP8/14 in Se & SF. 

Table 1 (n=32 Serum, n=14 Synovial Fluid)

Dx

StatisticalTest

Variable1

Variable2

Correlation

p value

DA

Correlation

Active Joint Count

ESR

Positive

p<0.05

MRP 8/14 SF

Positive

p<0.05

CRP

No Correlation

ns

MRP 8/14 SF

ESR

Positive

p<0.01

JIA & DA

Correlation

MRP 8/14 synovial fluid

MRP 8/14 serum

Positive

p<0.05

Dx

Statistical Test

Variable 1

Variable 2

Outcome

p value

JIA & DA

Paired t test

MRP 8/14 SF

MRP 8/14 Se

SF MRP8/14 signif.higher than matched SeMRP8/14

p<0.01

Conclusion

MRI with contrast remains the gold standard for diagnosis of synovitis.In reality,clinical assessment is the major diagnostic tool.DA is a more challenging condition than JIA,in light of confounding illness & the often-associated non-verbal state.In DA a simple biomarker of disease would be invaluable. We have shown that CRP is a poor marker of disease activity in JIA & DA so the need for a more specific biomarker is evident.Our preliminary results suggest that children with DA have elevated SF levels of MRP 8/14 that correlate to disease activity.SF concentrations of MRP 8/14 are significantly higher than their paired Se samples,however our results show significant positive correlation between the two.This suggests that Se MRP 8/14 levels are potential accurate markers of SF levels.MRP 8/14 may be a useful biomarker of disease activity in DA,aiding timely diagnosis & instigation of appropriate treatment,in turn,helping to improve clinical outcomes for this patient group.


Disclosure:

C. Foley,
None;

O. Killeen,
None;

E. J. MacDermott,
None.

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