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Rho-GTPase pathways may differentiate treatment response to TNF-alpha and IL-17A inhibitors in psoriatic arthritis

Sara Rahmati1,2, Darren D O'Rielly2, Quan Li1,3

  • 1Krembil Research Institute, UHN, 5-KD405, Krembil Discovery Tower, 60 Leonard Ave, Toronto, M5T 2S8, Canada.

Scientific Reports
|December 11, 2020
PubMed

Insights

Predicting psoriatic arthritis (PsA) treatment response is crucial. This study identifies Rho GTPase pathway rewiring as a potential biomarker for interleukin-17A inhibitor (17Ai) response in PsA patients.

Area of Science:

  • Immunology
  • Genetics
  • Computational Biology

Background:

  • Biological therapies have advanced psoriatic arthritis (PsA) treatment, but many patients do not respond or lose response over time.
  • A strategic approach for selecting biologic agents is needed due to high primary non-response rates and declining efficacy of sequential therapies.

Purpose of the Study:

  • To identify predictive biomarkers for response to biologic therapies in psoriatic arthritis.
  • To investigate differences in molecular pathways between responders and non-responders to tumor necrosis factor inhibitors (TNFi) and interleukin-17A inhibitors (17Ai).

Main Methods:

  • Transcriptomic profiling of CD4+ T-cells from 40 PsA patients initiating TNFi or 17Ai therapy.
  • Multi-omics and integrative computational analysis to identify differentially expressed genes (DEGs) and signaling pathways.
  • Correlation of gene expression profiles with treatment response, defined by Disease Activity Index for PsA (DAPSA) at 3 months.

Main Results:

  • Over 100 DEGs distinguished responders from non-responders for both TNFi and 17Ai therapies.
  • The Rho GTPase signaling pathway was significantly associated with response to 17Ai but not TNFi.
  • Specific genes within the Rho GTPase pathway, RAC1 and ROCKs, showed potential as predictive markers for 17Ai response.

Conclusions:

  • Rewiring of Rho GTPase signaling pathways may serve as a predictive biomarker for 17Ai response in PsA.
  • These findings highlight the potential for personalized medicine approaches in PsA treatment selection.
  • Further validation studies are required to confirm these molecular markers in larger patient cohorts.

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