Differential synovial tissue biomarkers among psoriatic arthritis and rheumatoid factor/anti-citrulline antibody-negative rheumatoid arthritis

Background: Differential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Ab^neg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Ab^neg RA and test their predictive value of therapeutic response.

Methods: Thirty-four PsA patients [12 DMARD naive and 22 non-responder to methotrexate (MTX-IR)] with peripheral joint involvement and 55 Ab^neg RA (27 DMARD naive and 28 MTX-IR) underwent US-guided ST biopsy and immunohistochemistry (IHC) for CD68⁺, CD3⁺, CD20⁺, CD21⁺, CD117⁺, and CD138⁺ cells. After study entry, each DMARD-naive patient started MTX therapy and was followed in an outpatient setting for at least 6 months to define the achievement of Minimal Disease Activity (PsA) and DAS remission (Ab^neg RA) status respectively. Each IR-MTX patient was treated according to EULAR recommendations.

Results: At study entry, IHC analysis revealed that PsA patients had comparable levels of lining and sublining CD68⁺ and sublining CD21⁺, CD20⁺, and CD3⁺ cells than Ab^neg RA, despite the therapeutic regimen. Moreover, regardless of the therapeutic scheme, PsA patients showed higher IHC score of CD117⁺ cells (p = 0.0004 and p = 0.0005 for naive and MTX-IR patients respectively) compared to Ab^neg RA patients. Conversely, Ab^neg RA patients showed higher IHC score of CD138⁺ cells, irrespective to the therapeutic scheme (p = 0.04 and p = 0.002 for naive and MTX-IR patients respectively). Analyzing the response rate to the therapeutic scheme, naive PsA patients reaching MDA status at 6 months follow-up, showed, at the study entry, lower IHC score of CD3⁺ cells compared to PsA patients not reaching this outcome (p = 0.02); conversely, naive Ab^neg RA patients reaching DAS remission status at 6 months follow-up, showed, at the study entry, lower IHC score of sublining CD68⁺ cells compared to Ab^neg RA patients not reaching this outcome (p < 0.001).

Conclusions: CD117⁺ and CD138⁺ cells are differentially distributed among PsA and Ab^neg RA. Histological analysis of ST may help to solve the clinical overlap between the two diseases and provides prognostic data about the therapy success.