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Abstract: SA-PO340

T-Regulatory and B-Regulatory Cells in Primary Membranous Nephropathy

Session Information

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. controlBaseline vs.6 vs.8 mon (ANOVA)Baseline vs. 6 monBaseline vs. 8 mon6 vs. 8 mon
TREGs
(CD3+ CD4+25Hi Fox3+ 127Lo)
7.55 ± 4.644.37±2.694.77±4.016.06±2.530.010.180.540.030.18
BREGs
(CD19 +, CD5+CD1dhiIL10)
3.19±2.751.25±1.721.29±1.804.52±4.760.00070.00030.830.00010.001

Values are expressed as frequencies. TREGs- Regulatory T cells, BREGs- Regulatory B cells

Funding

  • Government Support - Non-U.S.