title: Membranoproliferative glomerulonephritis: the role for laser microdissection and mass spectrometry.
abstract: Monoclonal gammopathy is increasingly recognized as a common cause of membranoproliferative glomerulonephritis (MPGN); however, establishing this diagnosis can be challenging. We report the case of a 58-year-old asymptomatic woman who presented with proteinuria with protein excretion of 5,000mg/d, microscopic hematuria, and normal kidney function. Kidney biopsy was consistent with MPGN pattern of injury. Immunofluorescence studies were positive for nonspecific segmental immunoglobulin M (IgM) and C3 staining. Electron microscopy showed subendothelial, subepithelial, and mesangial electron-dense deposits. The workup excluded an infectious or autoimmune disease, but IgG κ monoclonal protein was detected in serum at a concentration of 0.4mg/dL. Because there was a mismatch between the serum monoclonal protein (IgG κ) and immunofluorescence staining pattern (nonspecific IgM, no light chain restriction), laser microdissection and mass spectrometry were performed on the kidney biopsy tissue. This identified the deposits as monoclonal IgG κ, thereby leading to the diagnosis of monoclonal gammopathy-associated MPGN. Our case emphasizes the importance of searching for an underlying cause of MPGN, reviews the technique of laser microdissection-mass spectrometry, and highlights its application as a pathology tool for the evaluation of monoclonal gammopathy-related glomerulonephritis.
authors.affiliation: Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA; Division of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA. Electronic address: jaind@upmc.edu.
authors.forename: Deepika
authors.initials: D
authors.lastname: Jain
authors.affiliation: Geisenger Center for Health Research, Danville, PA.
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Green
authors.affiliation: Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA; Division of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Sheldon
authors.initials: S
authors.lastname: Bastacky
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Theis
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
mesh_terms: D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000502:physiology; D013058:Mass Spectrometry / Q000379:methods*; D042282:Microdissection / Q000379:methods*; D008875:Middle Aged
chemical_list: D007145:Immunoglobulin kappa-Chains
keywords: Membranoproliferative glomerulonephritis; laser microdissection; laser-capture microdissection–mass spectrometry (LCM-MS); mass spectrometry; monoclonal gammopathy; nephrotic; proteinuria; proteomics