Kidney Week

Abstract: SA-PO616

Patients with Membranous Nephropathy Show Increased Circulating T Follicular Helper (T_FH), T_H17, and Exhausted T Cells (T_EXH): Results from a Cross-Sectional Study Including Healthy and CKD Controls

Session Information

• Glomerular Diseases: Immunology, Inflammation - II
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

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

Chiara Cantarelli,

• Hartzell, Susan, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Susan Hartzell,

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

Andrea Angeletti,

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

Joaquin Manrique,

• Anderson, Lisa, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Lisa Anderson,

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

Emilie Chan,

• Donadei, Chiara, S. Orsola University Hospital, Bologna, Italy

Chiara Donadei,

• Fiaccadori, Enrico, Università di Parma, Parma, Italy

Enrico Fiaccadori,

• La Manna, Gaetano, S. Orsola University Hospital, Bologna, Italy

Gaetano La Manna,

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

Paolo Cravedi,

Background

Primary membranous nephropathy (MN) is characterized by the presence of antibodies to the podocyte, but studies characterizing abnormalities in circulating T and B cell populations are limited and generally include only healthy controls.

Methods

We performed a comprehensive flow-cytometric analyses of 38 T and B lymphocyte subpopulations, including intracellular staining for IFN-g, IL-4, and IL-17 production in 27 patients with MN (before initiating immunosuppressive therapy) and compared them with 12 healthy individuals and 22 patients with non-immune mediated chronic kidney disease (CKD) including diabetic nephropathy, hypertension, and APKD. We also measured 19 serum cytokines in MN patients and healthy controls.

Results

9 T and B cell subsets varied between MN and healthy subjects, but the only ones that differed between MN and both healthy and CKD controls included: CD4⁺CXCR5⁺PD1⁺ T follicular helper (T_FH), CD4⁺PD1⁺CD57^- T exhausted (T_EXH), and CD4⁺IL17⁺ T cells (T_H17) that were significantly higher in MN patients (Fig. 1A-D). TNF-a and IL-7 were also significantly higher in MN patients than in healthy controls (Fig. 1E-F).

Conclusion

Patients with MN display a unique immune phenotype characterized by increased T_FH, T_EXH, and T_H17 cells. Despite the associative nature of the study, inclusion of both healthy and CKD controls, strongly supports a pathogenic role for these cells.

Fig. 1. Percentages of T_FH (A), CD4⁺ T_EXH (B), T_H1 (C), T_H17 (D) cells in patients with membranous nephropathy (MN), in healthy controls (HC), and in patients with non-immune mediated chronic kidney disease (CKD). Serum TNF-a (E) and IL-7 (F) levels in MN patients and in HC.