From the Research
Targeting APRIL for IgA Nephropathy
- APRIL (A Proliferation-Inducing Ligand) is a key factor in the pathogenesis of IgA nephropathy (IgAN), and targeting it has shown promise as a potential therapeutic strategy 1, 2, 3, 4, 5.
- Studies have demonstrated that anti-APRIL antibody treatment can reduce albuminuria, serum IgA levels, and glomerular IgA deposition, as well as attenuate the inflammatory process mediated by fractalkine (FKN)-associated activation of monocytes 1.
- APRIL inhibition has been shown to reduce proteinuria and slow the rate of kidney disease progression by acting at an upstream level in IgAN pathogenesis 2, 3, 4.
- Several novel experimental agents targeting APRIL, including atacicept, telitacicept, zigakibart, and sibeprenlimab, are currently under investigation as potential therapies in IgAN 3.
- Preliminary results suggest that these agents are well-tolerated and reduce levels of galactose-deficient IgA1 (Gd-IgA1), with corresponding improvement in proteinuria 3, 4.
Mechanisms of APRIL in IgAN
- APRIL is involved in the regulation of activated B cells, the survival of long-lived plasma cells, and immunoglobulin (Ig) isotype class switching 2.
- APRIL mediates B-cell dysregulation and overproduction of pathogenic Gd-IgA1, leading to the formation of nephritogenic immune complexes in the kidney 3, 4.
- Elevated levels of APRIL are found in IgAN, correlating with the level of Gd-IgA1 and associating with more severe disease presentation and worse outcomes 3.
Therapeutic Potential of APRIL Targeting
- APRIL-targeting agents have shown potential as novel therapeutic agents for IgAN, effectively reducing proteinuria and Gd-IgA1 levels without significantly increasing adverse events 4, 5.
- VIS649, a humanized IgG2κ antibody targeting and neutralizing human APRIL, has demonstrated therapeutic efficacy in non-human primates, with a dose-dependent reduction of serum IgA levels and a reduction of IgA+, IgM+, and IgG+ B cells in the gut-associated mucosa 5.