Abstract: TH-PO0454
IgA-C3 Complex Is Associated with Disease Severity and Proteinuria Remission in IgAN
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - IgAN
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Li, Huixian, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Yuan, Xiaohan, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Xie, Xinfang, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Lu, Wanhong, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
Background
The canonical source of glomerular deposits in IgA nephropathy (IgAN) is circulating immune complexes. This study aims to identify the key composition of specific polymeric IgA complexes and investigate their clinical significance.
Methods
We first measured plasma Gd-IgA1, poly-IgA, and IgG-IgA complexes by ELISA in patients with IgAN, patients with IgA multiple myeloma (IgA-MM) and health controls. The specific IgA-C3 complex were then identified by mass spectrometry with purified plasma IgA-complexes from above participants. Next, IgA-C3 complex were measured in IgAN patients compared with patients with other glomerulopathy and healthy controls using a novel ELISA method. The results were validated in a two-month consecutive biopsy cohort. Finally, the longitudinal trend of IgA-C3 levels and the correlation with clinical severity and treatment responses were evaluated in another IgAN cohort.
Results
Mass spectrometry of purified IgA complexes identified 14 proteins with significantly different abundances between IgAN group, IgA-MM group and health controls, collectively pointing to alterations in complement pathway activity by KEGG enrichment analysis. Plasma and urinary IgA-C3 complex as candidate markers were measured. The levels of plasma IgA-C3 complex and urinary IgA-C3/UTP in IgAN were significantly higher than the non-IgAN glomerulopathy in the discovery cohorts. Receiver operating characteristic analysis showed that urinary IgA-C3/UTP complex distinguished IgAN from other glomerulopathy superior to plasma IgA-C3 (AUC 0.79 vs 0.62). Urinary IgA-C3 levels were also positively associated with baseline proteinuria (r=0.40, p<0.001) and urinary IgA-C3/UTP levels negatively correlated with eGFR (r=−0.33, p=0.006) in IgAN patients. These findings were validated in a two-month consecutive biopsy cohort, yielding consistent results. Moreover, in a prospective cohort of IgAN patients who received nefecon and other supportive treatments, baseline higher urinary IgA-C3/UTP was a risk factor for less 30% reduction of proteinuria at three months (logistic regression: OR 4.2, 95% CI: 1.1–17.3). Reduction in urinary IgA-C3/UTP complex levels correlated with proteinuria remission during follow-up.
Conclusion
The formation of high-molecular-weight complex of IgA-C3 plays a pivotal role in driving the pathogenesis, and was associated with the severity and treatment response of the disease.