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Abstract: PO1574

A Sporadic Case of Fibronectin Glomerulopathy in Which Mass Spectrometry Was Indispensable for the Diagnosis

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Kunitomo, Rie, Kyorin University, Tokyo, Japan
  • Kawakami, Takahisa, Kyorin University, Tokyo, Japan
  • Nagahama, Kiyotaka, Kyorin University, Tokyo, Japan
  • Hibino, Satoru, Kyorin University, Tokyo, Japan
  • Fukuoka, Kazuhito, Kyorin University, Tokyo, Japan
  • Komagata, Yoshinori, Kyorin University, Tokyo, Japan
  • Kaname, Shinya, Kyorin University, Tokyo, Japan
Introduction

Fibronectin glomerulopathy (FG) is an autosomal-dominant hereditary disease, which is caused by deposition of mutated fibronectin (FN). The immunostaining of FN is decisive for the diagnosis. We present a case of FG, in which FN was not detected with immunostaining and the detection of FN with mass spectrometry determined the diagnosis.

Case Description

A 60-year-old female with non-functional right kidney with calculi, 5-year history of proteinuria and 2-year history of hypertension presented with pretibial and palpebral edema. There was no family history of kidney diseases. Physical examination was significant for blood pressure of 176/98 mmHg and the edema. Laboratory test showed serum creatinine of 2.53 mg/dL, serum albumin of 2.3 g/L, urinary protein 5.8 g/day, and slight urinary glomerular RBCs. Anti-nuclear antibody, monoclonal protein, cryoglobulin, HCV, or hypocomplementemia was not detected. Open biopsy was performed. Light microscopy showed lobular glomeruli with mesangial expansion with PAS-positive material. Immunoglobulins, including κ and λ light chains, and complements were not deposited. Electron microscopy showed massive mesangial deposits with fibrillary structure. However, Congo red staining and immunostaining of DNAJB9 and fibronectin (IST-4 and IST-9) were all negative. Finally, the analysis of microdissected glomeruli with liquid chromatography/mass spectrometry (LC/MS) revealed abundance of FN, demonstrating the diagnosis of solitary FG.

Discussion

FG is caused by deposition of the soluble form of FN from serum, rather than the insoluble form produced by resident cells. Therefore, immunostaining with the monoclonal antibody IST-4, which can detect soluble FN, is usually positive in FG, while that with IST-9, which binds only to cellular FN, is negative. Although IST-4 staining was negative in the reported case, FN was detected with LC/MS. This might be due to a structural change of FN in the deposits, which hindered the binding of IST-4 antibody to FN. Furthermore, it was also confirmed that LC/MS is a powerful method to identify characteristics of unexplained glomerular deposits.