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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
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E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, and about one in three patients eventually progresses to end-stage renal disease. No specific therapies currently halt or reverse disease progression, underscoring the urgent need for new pathogenic insights and therapeutic targets. Animal models have been valuable for dissecting certain aspects of IgAN, such as IgA deposition, mesangial activation, and immune signaling, yet none reproduces the full spectrum of human disease. A major limitation is the absence of human IgA1 in mice and the lack of long-term progression to CKD. Bacterial upper respiratory tract infections, particularly Group A Streptococcus (GAS), have been implicated in IgAN initiation. GAS expresses a human IgA-binding region (arp4) on its M4 protein, and arp4 deposits have been observed in human IgAN kidneys. We hypothesized that administering recombinant arp4 into human IgA1 knock-in (IGHA1+/+) mice would promote IgA1–arp4 complex deposition in the mesangium, leading to pathological changes resembling human IgAN.
Arp4 was detected in human IgAN renal biopsies using rabbit anti-arp4 antibody. Wild-type C57BL/6J and IGHA1+/+ mice received tail-vein injections of recombinant arp4 protein (10 mg/kg twice weekly for 4 weeks, then weekly for 8 or 20 weeks). Renal function, serum biochemistry, and kidney histology were evaluated. Cell culture and proteomic analyses were also performed.
Arp4 detection in IgAN kidneys
Arp4 was present in 5 of 21 IgAN biopsies, localized to mesangial and capillary regions. Six of seven controls were negative, with one positive biopsy from post-streptococcal glomerulonephritis. Confocal imaging confirmed arp4 colocalization with PDGFR-β(+) mesangial cells and CD31(+) endothelial cells.
Human IgA1 and Gd-IgA1 in IGHA1+/+ mice
Both human IgA1 and galactose-deficient (Gd)-IgA1 were detected in serum and glomeruli. Arp4 injection markedly increased mesangial deposition of IgA1 and Gd-IgA1 without altering circulating levels.
Onset of proteinuria and hematuria
After 4 weeks of arp4 injection, IGHA1+/+ mice—but not WT mice—developed significant proteinuria and hematuria, which persisted for 3–6 months, demonstrating a specific effect of arp4 on human IgA1.
Glomerular pathology and renal dysfunction
PAS and Masson trichrome staining revealed progressive glomerular and tubulointerstitial fibrosis after 12–24 weeks of arp4 injection, accompanied by worsening renal function as measured by cystatin C, BUN, creatinine, and transcutaneous GFR.
Molecular signatures resembling human IgAN
Proteomic analysis of kidneys from 3-month arp4-injected IGHA1+/+ mice revealed alterations in extracellular region proteins, peptidase activity, complement binding, receptor signaling, and immune responses, closely paralleling molecular signatures of human IgAN.
We have established a novel mouse model that recapitulates key pathological, functional, and molecular features of human IgAN, providing a valuable platform for mechanistic studies and therapeutic development.
