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.
- 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.
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Table of Contents: PFGC 2021
Featured articles
Letter from the Editor
Guselkumab shows highest drug survival among systemic treatments
Genes in Psoriasis and Psoriatic Arthritis
HLA-C*06:02-positive patients on ustekinumab show higher drug survival in a real-world scenario
Protective factors identified against anti-drug antibody formation to adalimumab in psoriasis
Comorbidity in Psoriasis
Psoriasis associated with a higher cancer risk
Comorbidity and clinical features of psoriasis vary according to HLA-C*06:02 status
Psoriasis patients with cardiovascular comorbidity characterised by high systemic inflammation
Psoriasis Therapy: New Findings
Inhibition of heat shock protein: A novel way to treat psoriasis?
Guselkumab shows highest drug survival among systemic treatments
Tapering biologics: No alarming signs of increased anti-drug antibodies
Intermediate monocytes are possible predictors of response to secukinumab
Gut microbiota of psoriasis patients: less diverse and reduced functionality
COVID-19: What's New
DLQI scores underestimated during lockdowns?
TNF blockers likely beneficial for psoriatic patients with COVID-19
Patients on immunomodulators need 2 COVID-19 vaccinations before seroconversion
Paradoxical Reactions to Biologics
The Yin and Yang of opposing vectors: an explanation for side effects of biologics
Explaining arthropathy development through IL-4 and IL-13 blockade
Best of the Posters
Potential biomarker discovered for treatment response to ustekinumab
TNF inhibitor for immune-mediated inflammatory disease doubles the risk of paradoxical psoriasis
Secukinumab also tolerable in paediatric psoriasis patients
High treatment success with ixekizumab in patients with psoriasis and diabetes
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