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Gene Expression Study of Rheumatoid Arthritis Could Help Further Treatments

February 21, 2018
Studying synovial tissue samples uncovers some important patterns

A PPM Brief

Rheumatoid arthritis (RA) is one of the most common forms of arthritis, and further development of studies surrounding the inflammatory nature of the disease, especially in the hands and feet, may lead to optimal treatment strategies. Researchers recently published findings in Arthritis & Rheumatology1 that look to guide in this direction. Researchers sought out to refine histologic scoring of rheumatoid arthritis synovial tissue by training with gene expression data and machine learning.

By studying 20 histologic features on 129 synovial tissue samples, consensus clustering was performed on gene expression data from a subset of 45 synovial tissue samples. Support vector machine learning was used to predict gene expression subtypes using histology data as an input, and corresponding clinical data were compared across subtypes.1

Results indicated three distinct synovial subtypes:1

  • a highly inflammatory subtype characterized by extensive infiltration of leukocytes
  • a low inflammatory subtype characterized by enrichment in pathways including transforming growth factor beta, glycoproteins, and neuronal genes
  • a mixed subtype.

Researchers used the analysis to generate a histology-scoring algorithm that associated with levels of erythrocyte sedimentation rate (ESR), C-reactive proteins (CRP), and autoantibodies. Patients with highly inflammatory synovial subtypes exhibited higher levels of markers of systemic inflammation and autoantibodies. CRP were significantly correlated with pain in the high inflammatory group, but not the other subtypes.1

“Better understanding of the cause of pain in patients with little tissue inflammation is critical because non-inflammatory pain and synovial thickening could result in high tender and swollen joint counts in the absence of systemic inflammation,” the study authors wrote.

Researchers noted that while the high inflammatory subtype was associated with high synovial and systemic inflammation and autoantibodies, the low inflammatory subgroup was characterized by high neuronal and glycoprotein gene expression, as well as pain scores that were dissociated from elevated inflammatory markers.1

Results indicate a potentially important clinical distinction that mechanisms of pain may differ in patients with different synovial subtypes. Further assessments of small joint tissue from early rheumatoid arthritis patients to characterize important features for pathogenesis and predictive treatment responses are needed.1

Last updated on: February 23, 2018
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