Kidney Week

Abstract: SA-PO352

Complement Components Activation in Subjects with Primary FSGS Associates with Reduced Glomerular Expression of Decay Accelerating Factor (DAF)

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

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

Clara Fischman,

• Angeletti, Andrea, Mount Sinai Nephrology, Pianoro, Bologna, Italy

Andrea Angeletti,

• Donadei, Chiara, Nephrology, Dialysis and Kidney Transplantation, Bologna, Italy

Chiara Donadei,

• Malvi, Deborah, DIMES - University of Bologna, Bologna, Italy

Deborah Malvi,

• Cantarelli, Chiara, University Hospital, Parma, Parma, Italy

Chiara Cantarelli,

• La Manna, Gaetano, DIMES - University of Bologna, Bologna, Italy

Gaetano La Manna,

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

Paolo Cravedi,

Background

Split products of complement system activation (Ba, Bb, C4a and C5b9) have been identified in plasma and urine of subjects with primary FSGS at the time of diagnosis. We hypothesized that complement system activation in FSGS results from a downregulation of DAF (CD55), a cell surface expressed complement regulator.

Methods

We measured urine C3a and C5a in 23 subjects with primary FSGS at the time of diagnosis and serially thereafter and in 10 healthy controls by ELISA. We stained for C3d and DAF in renal sections of 10 subjects with primary FSGS and of 10 healthy controls (healthy sections obtained from nephrectomies for neoplasm).

Results

At the time of diagnosis, patients with primary FSGS have detectable urinary C3a and C5a, whose values are positively correlated with proteinuria (Figure 1A-B). Urine of healthy subjects was undetectable for both C3a and C5a. After therapy, proteinuria decline was paralleled by a reduction in both C3a and C5a in the urine (Figure 1C). In patients with primary FSGS, glomerular C3 deposits were associated with reduced expression of CD55 (Figure 1D).

Conclusion

Reduced glomerular expression of DAF is associated with glomerular C3 deposits and higher levels of complement components in the urine, suggesting a possible effect of DAF in complement activation during FSGS, and, possibly, in mediating renal injury.

Figure 1. C3a (A) and C5a (B) in the urine from FSGS patients at the time of biopsy. Levels of proteinuria, urinary C3a, and C5a at the time of biopsy and serially thereafter (C). Representative C3d deposit (IF) and DAF expression (IHC) in the glomeruli from FSGS patients and control kidneys (D).

Funding

• NIDDK Support