Abstract: TH-PO577
Establishment of a Human Hybridoma Cell Line That Produces IgG Autoantibody Involved in the Pathogenesis of IgA Nephropathy
Session Information
- Glomerular Diseases: Omics, Biomarkers, and Tools
October 24, 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
- Liu, Tzu Yu, Graduate Institute of Life sciences, Department of Medicine, National Defense Medical Center, Taipei, Taiwan
- Chen, Ann, Taiwan Autoantibody Biobank Initiative, Hualien Tzu Chi Hospital, Hualien, Taiwan
- Ka, Shuk-Man, Graduate Institute of Aerospace and Undersea Medicine, Department of Medicine, National Defense Medical Center, Taipei, Taiwan
Background
IgA nephropathy (IgAN) is an autoimmune disease, also the most common primary glomerulonephritis. Because the pathogenesis underlying IgAN remains largely known, there is still a lack of disease-specific and effective treatment for the renal disease. Recently, there is a key issue in the pathophysiology of galactose deficiency of O-glycans on the hinge region of IgA1, which has been considered as a main autoantigen (auto-Ag) involved in the development and progression of IgAN. However, the mechanistic pathways, including: (1) resultant production of IgG autoantibody (auto-Ab) against the galactose-deficient IgA1 (Gd-IgA1) auto-Ag triggered by the a auto-Ag; (2) subsequent formation of IgG-IgA1 immune complexes (ICs) and their potential in pathogenicity and clinical implications as well as (3) the property of the deposition of the ICs in the microenvironment of the glomeruli, in terms of the levels of intensity and distribution, are warranted further investigation.
Methods
To this end, our lab has successfully established exclusively a human hybridoma production platform suitable for preparing human IgG auto-Ab against Gd-IgA1 auto-Ag and the latter proteins. This strategy and the platform rendered a tremendous advantage for us to unravel the pathogenesis involving human IgG auto-Abs and IgA1 auto-Ags in this autoimmune disease towards the understanding of the immune and molecular pathogenesis of IgAN and further translational and clinical research topics. Our preliminary results show that using a SPYMEG human partner cell system and peripheral blood mononuclear cells from IgAN patients.
Results
We first time developed three human hybridoma cell lines from a single (the same) patient with IgAN namely Teddy71 (IgG auto-Ab) and 71D2 and 71C6 (two different IgA1 auto-Ags). In human macrophages and renal mesangial cells, the ICs formed by the human IgG auto-Ab with either of the two distinct human Gd-IgA1 auto-Ags clearly stimulated these cells to produce IL-1β, TNF-α, and IL-6 in significantly different levels, suggesting the nature of auto-Ags itself may also play a key role in resultant inflammatory responses in IgAN.
Conclusion
In consistence with these effects, the ICs containing human IgG auto-Ab and individual IgA1 auto-Ags was able to activate common pathway of complement system in vitro.
Funding
- Government Support – Non-U.S.