Abstract: SA-PO346
Patients with Membranous Nephropathy Display Unexpectedly Decreased Circulating T Follicular Helper (TFH) and TH17 Cells and Increased Regulatory B Cells (Breg)
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
- Cantarelli, Chiara, Az. Osp. Univ. Parma, Gattatico (Reggio Emilia), Italy
- Fischman, Clara, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Angeletti, Andrea, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Manrique, Joaquin, Complejo Hospital de Navarra, Pamplona, Spain
- Gandolfini, Ilaria, university hospital parma, Parma, Italy
- Chan, Emilie, Mount Sinai Hospital, New York, New York, United States
- Donadei, Chiara, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Tassiulas, Ioannis, Mount Sinai Hospital, New York, New York, United States
- La Manna, Gaetano, Complejo Hospital de Navarra, Pamplona, Spain
- Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background
Primary membranous nephropathy (PMN) is characterized by the presence of antibodies to the podocyte, but little is known on circulating T and B cell populations, especially the percentages of TFH and Breg.
Methods
We performed a comprehensive follow-cytometric analysis of 38 T and B lymphocyte subpopulations, including intracellular staining for IFN-g, IL-4, and IL-17 production in 16 patients with severe PMN and compared them with 12 age-matched healthy individuals.
Results
Within the T cell compartment, we found that patients with PMN had significantly fewer CD4+CD25+CD127lo Tregs (Treg; p=0.04), IL-17+CD4+ TH17 cells (p=0.01), and CD4+CXCR5+PD1+ TFH cells (p=0.02) than healthy controls (Figure 1A). While CD4+CD45RO+CD27- effector T cells were not differentially increased in PMN patients compared to healthy controls, they positively correlated with proteinuria in the PMN patients at baseline (r2=0.33; p=0.02). Within the B cell compartment, PMN patients had significantly fewer CD19+CD27+IgD+ unswitched B cells (p=0.01) and CD19+IgD+CD27-CD24loCD38lo naïve transitional B cells (p<0.0001) and significantly more CD19+CD25+CD71+ Bregs (p=0.046) than healthy controls (Figure 1B). Within PMN patients, we did not find a relationship between anti-PLA2R antibodies and any of the T or B cell subsets investigated.
Conclusion
Consistent with previous reports, patients with PMN display a unique immune phenotype characterized by reduced Treg and naïve B cell percentages. Unexpectedly, we newly found that PMN patients also display increased Breg, fewer TFH, and a positive correlation between CD4+ effector T cells and proteinuria, suggesting a pathogenic link.
Funding
- NIDDK Support