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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.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
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 is particularly prevalent in East Asia, especially Japan. Although dysregulation of the alternative complement pathway is central in atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3GN), its contribution to IgAN—particularly in East Asian populations—remains insufficiently elucidated. Structural alterations and rare variants in CFH, CFI, and CFHR genes may act as susceptibility or modifying factors shaping disease heterogeneity and progression.
We enrolled biopsy-proven IgAN cases (N=134) and age-matched juvenile ESRD controls (N=94). Copy-number variation in the CFHR cluster was assessed. Whole-genome sequencing identified structural variants and rare mutations in CFH, CFI, and CFHR. In IgAN, glomerular complement deposition (C3, C4) was evaluated by immunofluorescence to correlate genotype with histopathological activation.
The CFHR1/3 deletion was observed in 13 of 228 subjects overall (5.7%), including 5 of 134 IgAN cases (3.7%), consistent with its relative rarity in East Asian populations despite a directionally protective association in IgAN. CFHR gene rearrangements were detected in both IgAN and ESRD controls, suggesting partial—though not uniform—genetic overlap across renal diseases. The CFHR1/4 deletion was detected in 4 subjects overall and associated with relatively weak glomerular C3 deposition. Pathogenic or likely pathogenic variants (ACMG) in complement regulatory genes occurred in ~4% of IgAN cases—higher than reported in non–East Asian cohorts. Ethnicity-focused analyses suggested enrichment of East Asian–specific structural polymorphisms at the CFHR locus that may contribute to Japan’s disproportionate IgAN burden. Notably, across IgAN cases harboring DelCFHR1/3, DelCFHR1/4, or pathogenic complement regulatory variants, renal function tended to be relatively preserved, suggesting a potentially favorable prognosis. Biopsy-based staining further revealed heterogeneous C3 deposition patterns that correlated with CFHR structural variants.
Integrated MLPA, WGS, and renal biopsy analyses indicate that complement regulatory gene abnormalities function primarily as disease modifiers in IgAN. While there is genetic overlap with aHUS and C3GN, IgAN remains immune-complex–driven, with complement dysregulation acting as a secondary amplifier rather than a primary trigger. The identification of CFHR1/4 deletion in a subset of patients, together with enrichment of ACMG-classified pathogenic variants and the relative preservation of renal function in specific complement-related subgroups, underscores population-specific biology and supports complement modulation as a therapeutic avenue in East Asian IgAN.
