A1.9 Pilot work towards discovery of novel diagnostic biomarker for rheumatoid arthritis using combinations of chemokine receptor expression on peripheral blood cell-subsets. (31st January 2014) - Harrison, Stephanie
Abstract : Background and Objectives: Rheumatoid Arthritis (RA) is an autoimmune inflammatory joint disease resulting in joint damage and functional loss. Management is centred on early intervention, proven to prevent disabling joint damage and improve quality of life; however early intervention requires early and accurate diagnosis (1, 2) . Currently anti-citrullinated peptide antibody (ACPA) is the most clinically relevant diagnostic biomarker for RA however the sensitivity of ACPA in early RA is only ~40% despite high specificity (98%) ( 3 ) . Immune dysregulation early in RA pathogenesis has previously been described ( 4-8 ) . Our objective was to analyse chemokine receptor expression in early RA to identify novel diagnostic biomarkers. Material and Methods: Fresh peripheral blood samples from patients attending the Leeds early arthritis clinic were used. 21 were diagnosed with early RA and 25 with Non-RA including early undifferentiated arthritis and other inflammatory arthritis or non-inflammatory joint disease. All bloods were analysed using advanced 6-8 colour flow-cytometry for percentage of positive cells (%) and mean fluorescence intensity (MFI) expression of chemokine receptors CCR2, CXCR4, CCR5, CCR6 and IL6R on monocytes and lymphocyte subsets (natural killer (NK) cells, B cells, NKT-cells, CD4 + and CD8 + T-cells). Mann-Whitney-U and Chi-square tests were used to determine significant differences in single/combination receptor expression and cluster analysis was used to determine relevant receptors/cell subsets combination patterns. Results: When comparing early, treatment naïve RA (n = 21) with Non-RA early disease (n = 25) there were significant differences (p<0.050) in expression of CXCR4, CCR6 and IL6R notably on B, NK and NKT cells. Cluster analysis was then used to search for expression pattern. RA and non-RA grouped differently (p = 0.043) and CXCR4/IL-6R or CXCR4/CCR6 receptors combinations on NKT-cells were significant. Conclusions: Significant differences in receptor expression were identified between RA and non-RA diagnostic groups for both single and combinations of chemokine receptors in early disease patients. Importantly, differences were independent of and therefore of additional diagnostic value to ACPA testing. References: Quinn MA, Clin Exp Rheum 2003;21:S154-S7. Nell VPK, Rheumatology 2004;43:906-14. Goëb V, Joint Bone Spine 2009;76:343-9. Ponchel F, Blood 2002;100:4550-6. Ponchel F, ART 2005;7:R80-R92. Burgoyne CH, ARD 2008;67:750-7. Saleem B, ARD 2010;69:1636-42. Ponchel F, ARD 2013. Epub 2013, Aug 29.