Potential biomarker discovered for treatment response to ustekinumab

Investigation of blood immune cells found that IL-23 induced signal transducer and activator of transcription (STAT)3 nuclear translocation in mucosal-associated invariant T (MAIT) cells could serve as a biomarker of treatment response to ustekinumab. If further validated, this may offer future guidance for ustekinumab therapy.

Finding blood biomarkers able of predicting clinical response to systemic treatment of psoriasis is an emerging field of research. To evaluate whether or not STAT3 activation in IL-23 responsive cells could be a candidate for prediction, participants were enrolled from the Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium [1]. IL-23-induced STAT3 translocation was determined by imaging flow cytometry of peripheral blood mononuclear cells (PBMCs) and quantified. PBMCs were collected from the participants at baseline and during treatment with ustekinumab at weeks 1, 4, and 12.

The study cohort consisted of 10 adult Psoriasis Area and Severity Index (PASI) 75 responders and 10 PASI 75 non-responders at week 12, as well as 10 healthy volunteers, all matched by age, ethnicity, and sex. Mucosal-associated invariant T (MAIT) cells, IL-17 producing CD8 T cells, and IL-17 producing CD4 T cells were recognised as relevant immune cell populations. The baseline results for MAIT cells with IL-23-induced STAT3 translocation demonstrated no difference between healthy controls and participants with psoriasis. “We observed that in mucosal-associated invariant T cells or MAIT cells, STAT3 activation is significantly higher in ustekinumab PASI 75 responders compared with PASI 75 non-responders at baseline before therapy. Furthermore, we observed that STAT 3 translocation in MAIT cells at baseline significantly correlates with a clinical response at week 12 of ustekinumab therapy,” Mr Shane Solanky (King’s College London, UK) elaborated. For example, MAIT cells of psoriasis patients not experiencing PASI 75 on ustekinumab had significantly less IL-23-induced STAT3 translocation than PASI 75 responders. Overall, STAT3 translocation in MAIT cells, as well as IL-17 producing CD8 T cells were decreased by the ustekinumab treatment.

Exploring validity and reliability of baseline values of IL-23-induced STAT3 translocation in MAIT cells as a potential biomarker for response to ustekinumab, the receiver operator characteristic analysis resulted in an area under the curve of 99.1%, sensitivity of 100% and specificity of 87.5%. “Our research has identified IL-23-induced STAT3 translocation in MAIT cells as a potential biomarker predictive of response to ustekinumab, which warrants replication and further validation,” Mr Solanky concluded.

 

1. 
   
   1. Solanky S, et al. IL-23-induced STAT3 translocation in circulating MAIT cells is a potential biomarker of clinical response to ustekinumab in psoriasis. P60, Psoriasis from Gene to Clinic 2021, 9–11 December.

Copyright ©2021 Medicom Medical Publishers



Posted on 3 February, 2022