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

• 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

Chiara Cantarelli,

• Fischman, Clara, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Clara Fischman,

• Angeletti, Andrea, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Andrea Angeletti,

• Manrique, Joaquin, Complejo Hospital de Navarra, Pamplona, Spain

Joaquin Manrique,

• Gandolfini, Ilaria, university hospital parma, Parma, Italy

Ilaria Gandolfini,

• Chan, Emilie, Mount Sinai Hospital, New York, New York, United States

Emilie Chan,

• Donadei, Chiara, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Chiara Donadei,

• Tassiulas, Ioannis, Mount Sinai Hospital, New York, New York, United States

Ioannis Tassiulas,

• La Manna, Gaetano, Complejo Hospital de Navarra, Pamplona, Spain

Gaetano La Manna,

• Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Paolo Cravedi,

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 T_FH 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⁺CD127^lo Tregs (Treg; p=0.04), IL-17⁺CD4⁺ T_H17 cells (p=0.01), and CD4⁺CXCR5⁺PD1⁺ T_FH 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^-CD24^loCD38^lo 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 T_FH, and a positive correlation between CD4⁺ effector T cells and proteinuria, suggesting a pathogenic link.

Funding

• NIDDK Support