Background T cell activation depends upon a calcium signalling cascade that is regulated by voltage-gated potassium channels. Effector memory T cells (T_EM), which are implicated in the immunopathogenesis of autoimmune diseases, express relatively high levels of the potassium channel Kv1.3. Dalazatide is a potent peptide inhibitor of the Kv1.3 channel that has recently shown safety and efficacy in a Phase 1 b plaque psoriasis trial. Evidence suggests that inflammatory cytokine producing T_EM cells might be involved in the immunopathology of lupus nephritis. The objective of this study is to provide proof-of-principle ex vivo data for therapeutically targeting chronic T cell activation in systemic lupus erythematosus (SLE).

Materials and methods Peripheral blood mononuclear cells from paediatric and adult SLE patients as well as healthy controls were studied. T lymphocyte subsets were assayed ex vivo for Kv1.3 expression by flow cytometry. The effect of dalazatide on inflammatory cytokine expression by T_EM cells activated by thapsigargin/phorbol myristate acetate (PMA) or ionomycin/PMA was evaluated by intracellular cytokine staining.

Results Kv1.3 expression by CD8⁺ T_EM cells was significantly higher in patients with active lupus nephritis when compared to patients with inactive SLE or healthy controls. Dalazatide inhibited IFN-γ, IL-17 and TNF-α production by both CD4⁺ and CD8⁺ T_EM cells from SLE patients in a dose-dependent manner. Dalazatide-mediated inhibition was more significant in IFN-γ and TNF-α-expressing CD4⁺ T_EM cells from patients with active SLE compared to cells from patients with inactive disease.

Conclusions Ex vivo studies suggest that dalazatide inhibition of Kv1.3 on T_EM may be an effective strategy for treating SLE. In addition, Kv1.3 expression may be a useful biomarker of SLE disease activity.