B-LYMPHOCYTE CHEMOATTRACTANT (BLC/CXCL13): A POTENTIAL NOVEL DISEASE ACTIVITY MARKER OF RHEUMATOID ARTHRITIS

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown aetiology that affects 0.5–1% of the population. It is a polyarthritis characterized by inflammation, altered humoral and cellular immune responses and synovial hyperplasia, leading to destruction and subsequent loss of function of multiple joints. Multiple pathways are involved in the pathogenesis of RA and systemic proteins participating in these processes could be used as biomarkers to help define the disease activity in RA patients. Furthermore, the potential efficacy of novel compounds could be assessed by measurement of these markers in patients enrolled in clinical trials. Presently, the acute phase proteins CRP and ESR are the most validated markers of disease activity however, neither of these biomarkers is specific for RA.Objectives: The aim of this study was to identify and validate potential specific and sensitive markers of RA disease activity in plasma from RA patients and to correlate these makers with the disease activity score (DAS28).Methods: Thirty one RA patients were recruited and classified into two groups according to their disease activity score (DAS28): High disease activity RA group (HDRA) (DAS28 ≥ 3.2; n = 22) and Low disease activity RA group (LDRA) (DAS28 < 3.2; n = 9). EDTA-plasma samples were collected and 35 proteins were analysed using a multiplex platform (Pierce SearchLight Biotechnology, Inc). Five additional markers (including BLC) that were not included in the multiplex panel were also quantified using single Elisas. Plasma protein levels in the HDRA group were compared to the levels in the LDRA group using an ANOVA test. An additional non-parametric analysis (Kruskal-Wallis's test by ranks) for those proteins identified as being either not normally distributed or as having unequal variances in the analysis groups was performed. The Spearman's correlation coefficient by ranks was used to look at the relationships between levels of these markers and the DAS28 score.Results: From the 35 proteins analysed using the multiplex platform only the two acute phase proteins CRP and A-SAA were shown to be statistically significantly up-regulated in plasma from the HDRA patients compared to the LDRA cohort with fold changes on protein expression of 2.7 (p = 0.013) and 2.1 (p =0.043), respectively. BLC plasma levels, quantified by single Elisa, were also significantly increased in the HDRA patients compared to the LDRA group (fold change = 4.9, p = 0.005). Levels of this protein correlated well with the DAS28 score (r = 0.57).Conclusion: In this study, two previously described biomarkers of RA disease activity CRP and A-SAA, were identified as being statistically significantly up-regulated in plasma from HDRA patients compared to the LDRA cohort. Furthermore, we have shown that BLC levels, a B cell chemoattractant, are increased in plasma from RA patients and that its levels significantly correlate with the DAS28 score. These findings suggest that BLC may be a potential novel RA marker of disease activity and has further confirmed a previous observation in a separate cohort of RA patients(1).References: 1. Marion C. Dickson, et al. "Novel disease activity biomarkers of rheumatoid arthritis". Poster 326-ACR/ARHP Annual Scientific Meeting. Arthritis and Rheumatism. Washington, DC (USA). November 2006.Citation: Ann Rheum Dis, volume 66, supplement II, year 2007, page 452Session: RA – non-biologic treatment