Abstract: FR-PO821
Distinct O-glycoforms Profiles in the Hinge Region of Immunoglobulin A1 in Patients with IgA Nephropathy and IgA Type Multiple Myeloma
Session Information
- Glomerular Diseases: Inflammation and Immunology
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Xie, Xinfang, The Frist Affiliated Hospital of Xi'an Jiaotong University, Beijing, Outside the United States or Canada, China
- Lu, Wanhong, The Frist Affiliated Hospital of Xi'an Jiaotong University, Beijing, Outside the United States or Canada, China
- Zhang, Yong, West China Hospital, Sichuan University, Chengdu, China
Background
Galactose-deficient IgA1 (GdIgA1) is critical in the formation of circulating IgA polymer and poly-IgA immunodeposits in IgA nephropathy (IgAN). However, very rare patients with IgA type multiple myeloma(IgAMM) complicated by IgAN, although IgAMM patients had signigicantly high IgA1 and limited data also showed higher GdIgA1 composition in purified IgA1 from IgAMM patients. In this study we aimed to investigate the GdIgA1 levels, polyIgA1 levles and IgA1 O-glycoforms profiles in the hinge region (HR) of IgA1 from patients with the two diseases respectively.
Methods
25 patients with IgA type multiple myeloma and 66 patients with IgAN were included in the study. Plasma IgA, GdIgA1, CD89 captured polyIgA1 and IgA-IgG complex were detected by ELISA. Total IgA1 was purified from the plasma of the participants. The variation in O-glycoforms in HR of purified plasma IgA1 was evaluated by using mass spectrometry of EThcD-sceHCD MS/MS fragmentation mode .
Results
IgAMM patients included were older than IgAN patients (68.6±10 vs. 32±8 ys). Compared with IgAN patients, IgAMM patients had significantly higher levels of IgA1 (39.7±26.1 vs. 3.1±1.1 mg/ml, p<0.05), GdIgA1 (28.8±7.1 vs. 4.9±0.3 ug/ml, p<0.01) and CD89 captured polyIgA1(13.6±3.1 vs. 3.8±0.4 ug/ml, p<0.01). While GdIgA1/IgA levels were much higher in IgAN, and IgAN patients had higher IgA-IgG complexes. EThcD-sceHCD MS/MS showed the number of Nacetylgalactosamine (GalNAc) bound to one HR was higher in IgAN patients. The proportions of GalNAc4 (defined as O-glycans bound to one HR at 4 sites) and GalNAc5 were highest in all patients. The proportions of 3-5 galactose/HR were higher and 4 galactose/HR were with the highest proportions in both diseases (61.8%±11.1% vs. 52.8%±4.4% p<0.05, IgAMM vs. IgAN). Galactose deficiency profile per HR were investigated, we found deficiency of 1-2 galactose/HR were most common, and significant higher percentages of total galactose deficiency/HR were detected in IgAN than IgAMM group (87.7%±1.9% vs. 34.9%±6.1% p<0.01) . PCA analysis indicated that the O-glycoforms profiles of IgA1 differed greatly between the two diseases.
Conclusion
Distinct IgA1 O-glycoforms profiles in HR were showed in IgAN and IgAMM. Our data also supported higher levels of GdIgA1/IgA1 and IgA-IgG complexes play crucial roles in the pathogeneisis of IgAN.