Background/Purpose: Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects joints. There is still limited information of serum biomarkers suitable for effective monitoring of disease activity. To assess RA-associated serum protein signature using highly sensitive multiplex Proximity Extension ImmunoAssay (PEA) and its relationship with disease activity evaluated by activity score (DAS28).

Methods: We investigated the serum levels of 92 inflammation-related proteins in 78 Czech patients with RA and 38 age-matched healthy control (C) subjects using a highly sensitive innovative multiplex PEA (Proseek Multiplex, Olink Bioscience, Sweden). Statistical tests (Mann-Whitney U test, Benjamini-Hochberg correction, Spearman correlation) were performed using GenEx (Sweden), P-value ≤ 0.05 was considered as significant.

Results:

Top-ranked proteins distinguishing RA and C (P_corr<0.0001) were sTNFSF14, sulfotransferase 1A1, IL-6, axin 1, CCL7, caspase 8, oncostatin M, sirtuin 2, sTGFα, CCL3, sHGF, sCD40, STAMBP, FGF23, CXCL10, and sSLAMF1. Of them, upregulation of sulfotransferase 1A1, axin 1, and GDNF was not reported in RA yet. Disease activity positively correlated with CCL20 (r=0.495, P=0.000004), CCL7 (r=0.442, P=0.00005), CXCL1, CXCL9, IL-6, sCDCP1, GDNF, CXCL10 (r>0.30, P<0.006), and negatively correlated with IL-12B and sCD244 (r<-0.304, P<0.007). Subanalysis of protein pattern in patient phenotypes is ongoing.

Conclusion: Among the entire panel, the chemokines CCL20, CCL7, CXCL1, CXCL9, CXCL10 and GDNF appeared to be the most useful serum markers for evaluation of the disease activity of patients with RA. Further multivariate analysis is needed to identify pattern associated with high disease activity.

Acknowledgement: Grant support: MZ CR VES15-28659A, IGA_LF_2017_009

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/relationship-between-serum-protein-pattern-and-high-disease-activity-in-patients-with-rheumatoid-arthritis/