Evidence from multicenter clinical studies and humanized mouse models indicates that glomerular mesangial IgA2 deposition contributes to the pathogenesis of IgA nephropathy - PubMed
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- #IgA nephropathy
- #glomerular deposition
- #IgA2
- Evidence from multicenter clinical studies and humanized mouse models shows that glomerular mesangial IgA2 deposition contributes to IgA nephropathy (IgAN) pathogenesis.
- IgA2 lacks a 13-amino acid segment found in IgA1, which contains O-glycosylation sites, making its role in IgAN controversial.
- Laser capture microdissection coupled with mass spectrometry (LCM/MS) detected IgA2(m1) and IgA2(m2) in IgAN glomeruli, though less abundant than IgA1.
- Multicenter immunofluorescence analysis revealed mesangial IgA2 in over 98% of IgAN cases, correlating with chronic lesions and kidney dysfunction.
- Humanized IgA2 mouse models exhibited IgA2 mesangial deposition, tubular atrophy, stronger complement C3 activation, and interstitial macrophage infiltration compared to IgA1 mice.
- The study highlights IgA2's role in IgAN, demonstrating its capacity for glomerular deposition, complement activation, and distinct histopathological injury patterns.