Abstract: SA-PO340
T-Regulatory and B-Regulatory Cells in Primary Membranous Nephropathy
Session Information
- Glomerular Diseases: Immunology and Inflammation - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Ramachandran, Raja, PGIMER, Chandigarh, India
- Kaundal, Urvashi, PGIMER, Chandigarh, India
- Rakha, Aruna, PGIMER, Chandigarh, India
- Gupta, Krishan Lal L., Postgraduate Institute of Medical Education & Research, Chandigarh, India
- Jha, Vivekanand, George Institute for Global Health, New Delhi, India
Background
Primary membranous nephropathy (PMN) is an antibody-mediated disease. Both T-regulatory (TREGs) and B-regulatory (BREGs) cells are decreased in patients with autoimmune disease. The data on TREGs and BREGs in PMN is very scanty. We evaluated the TREG and BREG population in patients of PMN treated with cyclical cyclophosphamide and steroid therapy (cCTX/GC).
Methods
Twenty-four patients of PMN and 10 healthy controls were enrolled in the study at Nehru Hospital, PGIMER, Chandigarh. All the patients were resistant to restrictive strategy and were treated with cCTX/GC therapy. The proteinuria, serum creatinine and serum albumin were tested at monthly intervals and blood samples were collected prior to starting cCTX/GC and at 6 and 8 (2 months wash out) months of therapy. The peripheral blood mononuclear cells (PBMCs) were isolated from the collected blood samples using density gradient centrifugation. PBMCs after staining with fluorochrome-conjugated antibodies were then subjected to flow cytometric analysis for detection of TREGs (CD3+CD4+CD25hiCD127loFoxP3+) and BREGs (CD19+CD5+CD1dhiIL10+) at all time-points. TREGs and BREGs are presented as the percentage of CD3+CD4+ and CD19+ cells, respectively.
Results
The mean proteinuria, serum albumin and creatinine at baseline was 8.74±4.85 g, 2.33±0.80 g/dL and 1.06± 0.53 mg/dL, respectively. Patients with PMN had a lower percentage of TREGs and BREGs compared to healthy controls (p<0.05). There was a significant increase in both BREGs and TREGs with the treatment at 6 and 8 months (Table). The rise in both BREGs and TREGs were apparent after stopping (8 months) immunosuppressive therapy (Table).
Conclusion
As compared to the healthy controls, patients with PMN displayed a lower percentage of TREGs and BREGs. Both TREGs and BREGs significantly improved with disease-specific therapy. The increase in both the regulatory cells is apparent after two months of stopping cCTX/GC.
BREGs and TREGs in Primary Membranous Nephropathy
| Control (n=10) | Baseline (n=24) | 6 mon (n=24) | 8 mon (n=24) | Baseline vs. control | Baseline vs.6 vs.8 mon (ANOVA) | Baseline vs. 6 mon | Baseline vs. 8 mon | 6 vs. 8 mon | |
| TREGs (CD3+ CD4+25Hi Fox3+ 127Lo) | 7.55 ± 4.64 | 4.37±2.69 | 4.77±4.01 | 6.06±2.53 | 0.01 | 0.18 | 0.54 | 0.03 | 0.18 |
| BREGs (CD19 +, CD5+CD1dhiIL10) | 3.19±2.75 | 1.25±1.72 | 1.29±1.80 | 4.52±4.76 | 0.0007 | 0.0003 | 0.83 | 0.0001 | 0.001 |
Values are expressed as frequencies. TREGs- Regulatory T cells, BREGs- Regulatory B cells
Funding
- Government Support - Non-U.S.