Treating AAV by targeting T cell responses

Abstract

Glucocorticoids are currently used to induce remission in patients with antineutrophil cytoplasmic antibody glomerulonephritis (ANCA-GN), but these drugs carry a high risk of adverse effects and infection. Targeting T cells through cytokine inhibition might represent an alternative therapeutic approach, according to a new study by Christian Krebs, Ulf Panzer and colleagues.

A digital pharmacology analysis identified the monoclonal antibody ustekinumab, which targets IL-12 and IL-23, as a candidate treatment for targeting T_H1 and T_H17 cells. These T cell subsets were confirmed to be enriched in inflamed areas of the kidney in an additional cohort of patients with ANCA-GN using flow cytometry. From this cohort, four patients with relapsing disease were treated with ustekinumab, in addition to standard-of-care cyclophosphamide and steroids. Over 26 weeks, treatment led to a positive clinical and serological response without causing serious adverse effects.