ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

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

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