Transcript
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Dr. Rizk:
Hello, this is CE on ReachMD, and I'm Dr. Dana Rizk. Here with me today is Dr. Yusuke Suzuki. Our topic today is the mechanistic role of APRIL and its potential as a disease-modifying target in IgA and nephropathy.
Dr. Suzuki, welcome. Can you tell us about the role of APRIL in the disease pathogenesis of IgA nephropathy?
Dr. Suzuki:
Thank you, Dana, for your question. So as many of you know, the multi-hit theory is currently widely accepted in the pathogenesis or pathological hypothesis for IgA nephropathy.
So this hypothesis proposes that the immune complex formed by the IgA molecule with all glycol modification in the region of IgA1 molecule, particularly the galactose deficiency in IgA1, so-called Gd-IgA1, as a hit 1 in this hypothesis. An autoantibody against Gd-IgA1 as hit 2. So it’s immune complex as hit 3 deposit in the glomerulus and causes the inflammatory injury.
The APRIL molecule is thought to play a key role in the production of this pathogenic Gd-IgA1 within B cells. So this means that drugs targeting the APRIL molecule suppress the production of these pathogenic IgA at the very beginning of this disease.
Dr. Rizk:
Thank you for this overview. So it makes sense then that using anti-APRIL therapies would affect the disease and cause what we refer to now as disease modification, because it really targets the heart of the immunologic aspect of IgA nephropathy pathogenesis and, as you mentioned, really starts at the top, at the level of hit 1.
So, Dr. Suzuki, what are APRIL levels -- what do they look like in the Asian population?
Dr. Suzuki:
So we have some clinical data. So they show that the Asian patients with IgA nephropathy genetically exhibit elevated serum levels of APRIL. Furthermore, the reports from China indicate that patients have higher serum levels of APRIL compared to a healthy individual, and that consideration correlates with blood Gd-IgA1 level.
Additionally, reports from South Korea have shown that serum APRIL levels correlate with the renal prognosis in IgA nephropathy.
Dr. Rizk:
So it sounds like Asian patients have a strong APRIL-driven biology, and hopefully some of these new anti-APRIL therapies would be helpful to treat them.
Well, this has been a great micro-discussion. Our time is up. Thank you so much for joining me, Dr. Suzuki, and thank you all for listening.
Dr. Suzuki:
Thank you very much.
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