Synovial tissue heterogeneity in rheumatoid arthritis in relation to disease activity and biomarkers in peripheral blood

Abstract

Objective To investigate the clinical relevance of synovial tissue subtypes in rheumatoid arthritis (RA) and to search for peripheral blood (PB) markers that may serve as biomarkers for tissue subtypes. Methods Gene expression analysis using complementary DNA microarrays was applied on paired synovial tissue biopsy and PB samples obtained from 17 RA patients. Molecular tissue subtypes were correlated with histologic parameters (CD3, CD22, CD38, CD68, CD163, tumor necrosis factor α, intercellular adhesion molecule 1, vascular cell adhesion molecule, and E‐selectin), disease characteristics, and PB markers. PANTHER classification was used for pathway analysis. Results Genomic subtyping of high‐ and low‐inflammation rheumatoid synovial tissues based on gene expression profiles exactly matched immunohistochemical classification. The patients with the high‐inflammation tissue type had higher Disease Activity Scores in 28 joints, higher C‐reactive protein levels, higher erythrocyte sedimentation rates, increased numbers of platelets, and shorter disease durations. Comparative analysis of PB gene expression profiles yielded no statistically significant differences between the 2 tissue groups at the single‐gene expression level. PANTHER pathway analysis revealed a significant association of increased protein biosynthesis with high‐inflammation tissue. Conclusion High‐inflammation tissue is associated with more severe disease and shorter disease duration. While pathway‐level analysis revealed that coordinate differential expression of genes involved in protein synthesis in PB is associated with high‐inflammation tissue types, differential tissue pathology was not reflected in the PB by differential expression of single genes.

Synovial tissue research: a state-of-the-art review

“…Different subtypes of RA patient synovia have also been characterised by gene expression analysis. 112,113 Geneexpression variance among RA patients has been described impacting several pathways involved in cell proliferation, cell survival, angiogenesis and regulation of inflammation. 114 …”

A novel Saa3-promoter reporter distinguishes inflammatory subtypes in experimental arthritis and human synovial fibroblasts

“…A recent study by van Baarsen et al has shown that a high inflammatory synovial gene-expression profile correlates with a higher disease activity, C reactive protein (CRP) levels and erythrocyte sedimentation rates (ESRs), increased platelet numbers and a shorter disease duration in RA patients 12. This indicates that there is a diagnostic value of determining low and high inflammatory subtypes of synovial tissue.…”

Gene Expression Profiling in Rheumatoid Arthritis

“…Van Baarsen and colleagues studied the synovial tissue gene expression profiles in relation to immunohistochemical scores and disease parameters. The results demonstrated an excellent correlation between molecular and immunohistochemical scoring (van Baarsen et al, 2010b). Moreover, the high inflammation tissue type was predominantly observed in patients with high disease activity and short disease duration, suggesting temporal differences in the inflammatory status during the course of the disease (Firestein & Zvaifler, 2002).…”

“…The identification of processes and biomarkers in PB may facilitate informative studies of a relation between tissue type and clinical parameter. The notion that molecular heterogeneity is present in both the synovial as well as the PB compartment makes it tempting to speculate on molecular and biological features that reflect the tissue pathology (van Baarsen et al, 2010b). However, paired analysis of peripheral blood and affected synovium from 17 patients with RA revealed that differential tissue pathology was not reflected in the PB by differential expression of single genes.…”