# Advances in Novel Biologics Targeting BAFF/APRIL in the Treatment of IgA Nephropathy

## TL;DR

This paper explores new biologics targeting BAFF/APRIL to treat IgA nephropathy, a kidney disease, by reducing harmful antibody production and improving patient outcomes.

## Contribution

The paper provides a comprehensive summary of the clinical progress and mechanisms of BAFF/APRIL-targeted biologics in IgA nephropathy treatment.

## Key findings

- BAFF and APRIL biologics reduce galactose-deficient IgA1 and proteinuria in IgA nephropathy patients.
- Clinical trials show these biologics stabilize eGFR and improve symptoms via B-cell modulation.
- Long-term risks like infection and drug resistance require further monitoring in clinical settings.

## Abstract

IgA nephropathy is a common glomerular disease and a leading cause of progression to end-stage renal disease.

BAFF and APRIL induce excessive B-cell activation by binding to receptors TACI, BCMA, and BAFF-R, leading to the overproduction of galactose-deficient IgA1 (Gd-IgA1).

Mechanism of action of BAFF/APRIL biological agents in treating IgA nephropathy.

Clinical trial progress of BAFF/APRIL biological agents in treating IgA nephropathy.

IgA nephropathy (IgAN) is the most common primary chronic glomerular disease worldwide. Its clinical features include proteinuria and complement pathway activation, which are the strongest predictors of progression to renal failure. This disease can occur at any age. Approximately 30–40% of IgAN patients progress to end-stage renal disease (ESRD) within 20–25 years after diagnosis, making it one of the major causes of ESRD. As understanding of the autoimmune development of IgA nephropathy (IgAN) grows, research shows that BAFF and APRIL promote B-cell activation by binding to the receptors TACI, BCMA, and BAFF-R. This results in the overproduction of galactose-deficient IgA1 (Gd-IgA1), which helps drive the progression of IgA nephropathy. B-cell and plasma cell-targeted therapies, such as biologics against BAFF/APRIL, can precisely and effectively improve patient symptoms. Corresponding agents have now been successfully developed and are administered via subcutaneous or intravenous injection. Clinical trials have demonstrated the significant effectiveness of this approach, especially in reducing proteinuria, stabilizing eGFR, and lowering Gd-IgA1 levels. Although current trial data for BAFF/APRIL-targeted biologics in IgA nephropathy are promising, these new treatments need ongoing clinical monitoring for long-term infection risks and potential drug resistance. This article focuses on the application of BAFF/APRIL biologics in the treatment of IgA nephropathy, addressing gaps in existing literature. While prior studies have emphasized the mechanisms of action of these drugs in IgA nephropathy, they have lacked a comprehensive summary of the current status of specific drug research and clinical progress.