During early rheumatoid arthritis (RA), the presence of certain cellular and molecular synovial signatures can be used to determine disease severity or progression as well as therapeutic response, according to results published in the Annals of the Rheumatic Diseases. These results may contribute to a more precise RA taxonomy that can improve therapeutic targeting and patient outcomes.

The study included treatment-naive participants with early RA (<12 months symptoms duration; n=144). Participants underwent ultrasound-guided synovial biopsy at baseline and 6 months after disease-modifying antirheumatic drug initiation.

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The researchers analyzed the synovial biopsies for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes. They used differential gene expression analysis and logistic regression to determine variables that correlated with treatment response and predicted radiographic progression.

Through cellular and molecular analyses of synovial tissue, the researchers identified 3 pathology groups in early RA:

  • lympho-myeloid, dominated by the presence of B cells and myeloid cells;
  • diffuse-myeloid with myeloid lineage predominance but poor in B cells; and
  • pauci-immune, characterized by few immune cells and many stromal cells.

Using longitudinal correlation of molecular signatures, the researchers found that the elevation of myeloid- and lymphoid-associated gene expression was significantly correlated with disease activity, acute phase reactants, and 6-month disease-modifying antirheumatic drug response.

The results also indicated that the elevation of synovial lymphoid-associated genes was correlated with autoantibody positivity. Elevation of osteoclast-targeting genes predicted radiographic joint damage progression at 12 months.

Compared with participants with lymph-myeloid and diffuse-myeloid pathology, those with predominant pauci-immune pathology had less severe disease activity and radiographic progression.

“These data support the evaluation of such biomarkers within randomised clinical trials with the aim of enriching response to current biological therapies by targeting the specific cognate pathways expressed in some patients but not others,” the researchers wrote.

Reference

Humby F, Lewis M, Ramamoorthi N, et al. Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients [published online March 16, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2018-214539