Photo Credit: Mohammed Haneefa Nizamudeen

The following is a summary of “Immune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis,” published in the September 2024 issue of Nephrology by Engesser et al.

Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a severe autoimmune disease that can lead to kidney failure, primarily due to crescentic glomerulonephritis (GN). Most patients with ANCA-GN currently receive non-specific immunosuppressive agents, which can have severe side effects and may not be fully effective.

Researchers conducted a retrospective study identifying the inflammatory niches in kidney samples from patients with ANCA-GN and exploring potential targeted therapies. 

They conducted spatial and single-cell transcriptome analyses on kidney samples from 34 patients with ANCA-GN. This research focused on identifying proinflammatory, cytokine-producing CD4⁺ and CD8⁺T cells as a pathogenic signature. The transcriptomic profiles were then used for digital pharmacology to find effective therapeutic options.

The results showed that ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, is the most promising therapeutic drug. Moreover, 4 Patients with relapsing ANCA-GN were treated with ustekinumab alongside low-dose cyclophosphamide and steroids, administering ustekinumab subcutaneously (90 mg) at weeks 0, 4, 12, and 24. After a follow-up of 26 weeks, the treatment was well-tolerated. It resulted in clinical responses, including improved kidney function and Birmingham Vasculitis Activity Score, for all patients with ANCA-GN.

Investigators concluded that targeting harmful T cells with ustekinumab in patients with ANCA-GN shows promise as a treatment option, indicating a strong need for more research in clinical trials to explore its effectiveness further. 

Source: nature.com/articles/s41467-024-52525-w