Vasculitis & polymyalgia rheumatica
Kv1.3 blockade by ShK186 modulates CD4+ effector memory T-cell activity of patients with granulomatosis with polyangiitis
Authors' conclusion
Modulation of cellular effector function by ShK-186 may constitute a novel treatment strategy for GPA with high specificity and less harmful side effects.
Study context
- Population
- Peripheral blood samples from patients with granulomatosis with polyangiitis (GPA) in remission and age- and sex-matched healthy controls (HCs)
- Participants
- 27 vs 16
- Comparison
- Pre-incubation with ShK-186 vs without ShK-186
- GPAn = 27
- HCsn = 16reference
- Outcome
- Effect of ShK-186 on cytokine production (IFNγ, TNFα, IL-4, IL-17, IL-21) within total and subsets of CD4+TH cells
Methodological detailsin vitro, flow cytometry, age- and sex-matched healthy controls, Samples pre-incubated in vitro with or without ShK-186, then stimulated with phorbol myristate acetate, calcium ionophore and brefeldin-A
- In vitro
- Flow cytometry
- Age- and sex-matched healthy controls
- Samples pre-incubated in vitro with or without ShK-186, then stimulated with phorbol myristate acetate, calcium ionophore and brefeldin-A
Main finding
As reported in the abstract
Cytokine production in CD4+TH cells with ShK-186 in vitro
- ShK-186 reduced expression level of IFNγ, TNFα, IL-4, IL-17 and IL-21 in CD4+TH cells from patients with GPA in vitro
- ShK-186 predominantly inhibited cytokine production of CD4+TEM cells (sorted CD4+T cell subsets)
- ShK-186 reduced pro-inflammatory cytokine production to the level seen in CD4+TH cells from HCs
Original publication
Kv1.3 blockade by ShK186 modulates CD4+ effector memory T-cell activity of patients with granulomatosis with polyangiitis. Rheumatology (Oxford). Published 22 April 2023. doi:10.
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