Abstract: TH-PO449
Immunological Profile in Nephrotic Patients With Minimal Change Nephrotic Syndrome Is Distinct From Focal Segmental Glomerulosclerosis
Session Information
- Glomerular Diseases: Podocytopathies and Nephrotic Syndromes
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1302 Glomerular Diseases: Immunology and Inflammation
Authors
- Chan, Chang-Yien, Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Lu, Liangjian, Khoo Teck Puat-National University Children’s Medical Institute, National University Health System, Singapore, Singapore
- Teo, Sharon, Khoo Teck Puat-National University Children’s Medical Institute, National University Health System, Singapore, Singapore
- Lam, Kong Peng, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
- Ng, Kar Hui, Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Yap, Hui Kim, Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Background
We have previously shown that immunological subtypes in patients with childhood-onset idiopathic nephrotic syndrome (INS) in relapse were different between focal segmental glomerulosclerosis (FSGS) and minimal change nephrotic syndrome (MCNS), where a subgroup of FSGS patients demonstrated T-cell downregulation of stimulated CD154 and IFNg. This study aimed to determine if the immunological profiles are indeed distinct in FSGS and MCNS by further characterizing the T-cell transcription regulator gene expression and phenotype.
Methods
A total of 38 patients with childhood-onset INS in relapse consisting of 21 MCNS (median age 14 years, range 2-35 years) and 17 FSGS (median age 13 years, range 4-25 years) and 8 healthy controls (median age 19 years, range 4-27 years) were recruited. Gene expression of T-cell transcription regulators were performed on purified stimulated CD4 T-cell using real-time PCR. Lymphocyte subset (T-cell exhaustion marker (PD1), T-cell subsets: memory (CD45RA, CCR7), naïve (CD45RO, CD62L), follicular helper (CXCR5, CD127), Treg (FoxP3, CTLA-4) and invariant NKT (TCR Vα24-Jα18) staining was performed by the lysed whole blood method. Statistical analysis was done using Mann-Whitney U tests.
Results
Gene expression of Th2 (GATA3) and Th17 (RORGT and RORC) transcription factors were significantly upregulated in relapse MCNS compared to relapse FSGS (Table 1). Moreover, gene expression of NFATC2, transcription factor regulating RORγt transcription through RORC, was also significantly increased in relapse MCNS. Gene expression of MAF and CMIP (C-Maf-inducing protein) were significantly higher in relapse MCNS compared to healthy controls. Phenotype analysis showed that relapse FSGS had significant upregulation of Tfh cells (CXCR5) (18.0%±1.0%) compared to relapse MCNS (14.0%±1.1%) (P=0.005) and controls (11.5%±0.5%) (P<0.001).
Conclusion
We have demonstrated distinct T-cell profiles between relapse MCNS characterized by Th2 and Th17 phenotypes, and relapse FSGS characterized by Tfh phenotype.
Funding
- Government Support – Non-U.S.