Dual Inhibition of BlyS and APRIL in IgA Nephropathy

Opinion
Video

Nephrology experts explore the role of dual inhibition of BlyS and APRIL in the treatment of IgAN, and how this can impact disease pathogenesis.

This is a video synopsis/summary of a panel discussion involving Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD.

Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD, discuss the modulation of B cells, specifically targeting cytokines Baff and April, crucial for IgA class switch recombination. Dr Rovin draws on his experience in lupus nephritis, where the Baff inhibitor Belimumab showed efficacy in inducing renal responses and preserving kidney function. He highlights the exciting data emerging from BAFF and APRIL inhibitors, particularly in the context of IgA nephropathy (IgAN).

The discussion delves into the novel class of drugs that modulate B cells and inhibit BAFF and APRIL simultaneously. Dr Rovin expresses fascination with the data indicating a depletion of galactose-deficient IgA, a subset thought to be responsible for kidney damage. He speculates on the mechanisms by which these drugs may selectively target aberrant IgA molecules, suggesting a potential sensitivity of specific B cell clones to growth factors.

Dr Barratt emphasizes the importance of evaluating both efficacy and safety when assessing these drugs. The safety concern with B cell modulation revolves around potential effects on IgG, which is crucial for lifelong immunity and immunological memory. However, the data suggests that IgG is relatively protected, minimizing the risk of hypogammaglobulinemia associated with some B cell-depleting therapies.

The conversation touches on the autoimmune aspect of IgAN, where aberrant IgA molecules may induce IgG autoantibodies. Drawing parallels with lupus, Dr Rovin discusses the potential impact of Baff inhibition on autoantibody production and the long-term benefits of having a therapy that sticks around to manage relapsing autoimmune diseases like IgAN.

Both experts agree on the need for longer-term maintenance therapies in glomerular diseases like IgAN and emphasize the importance of biomarkers for monitoring disease activity and progression. The discussion reflects a nuanced approach to treatment, acknowledging the complexities of these autoimmune conditions and the necessity for personalized, sustained therapeutic strategies.

Video synopsis is AI-generated and reviewed by HCPLive editorial staff.

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Kaitlin Mayne, MBChB | Credit X.com
Alexandra Louise Møller, MS, PhD | Credit: LinkedIn
Jonathan Barratt, MD | Credit: IgA Nephropathy Foundation
Fadi Fakhouri, MD, PhD | Credit: University of Lausanne
Helen Colhoun, MD | Credit: University of Edinburgh
Digital illustration of kidneys | Credit: Fotolia
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