Unmasking the C3ulprit
November 05, 2022 | 10:00 AM - 12:00 PM
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Unmasking the C3ulprit
- Glomerular Diseases: IgA and Complement-Mediated GN
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1302 Glomerular Diseases: Immunology and Inflammation
- Ma'ayah, Audai, University of Nebraska Medical Center, Omaha, Nebraska, United States
- Benes, Brian, University of Nebraska Medical Center, Omaha, Nebraska, United States
- Borghoff, Kathleen, University of Nebraska Medical Center, Omaha, Nebraska, United States
- Foster, Kirk W., University of Nebraska Medical Center, Omaha, Nebraska, United States
- Ravipati, Prasanth, University of Nebraska Medical Center, Omaha, Nebraska, United States
Kirk W. Foster,
C3 glomerulonephritis (C3GN) is a rare disease with kidney biopsy findings typically showing a proliferative pattern of injury with C3 deposition on immunofluorescence (IF), along with an absence of immunoglobulin (Ig) staining. However, in certain cases, it is important to pursue paraffin IF, which can unmask deposited Ig that is negative on routine IF staining. The aim of this case report is to illuminate the importance of paraffin IF to help distinguish cases of C3GN from immune complex GN.
A 22-year-old man with no chronic medical history presented with complaints of arthralgias and sore throat and was found to have acute kidney injury. He was without rash, synovitis, or peripheral edema. Serum creatinine was 4.37 mg/dL, urinalysis showed numerous dysmorphic red blood cells, and spot protein to creatinine ratio was 2.5. Serologic evaluation showed low C3, low C4, and a positive anti-nuclear antibody. Additional antibody testing, streptococcal testing, serum protein electrophoresis with immunofixation, and infectious diseases evaluation were negative. Kidney biopsy showed mesangioproliferative glomerulonephritis involving all glomeruli, with IF staining positive only for C3 in the glomerular capillary walls. A preliminary diagnosis of C3GN was made. However, electron microscopy (EM) showed fibrillary-like substructure within subendothelial deposits and intracellular rod-like crystals, which raised suspicion for masked glomerular Ig deposits. Therefore, we performed paraffin IF which showed IgG staining with kappa restriction along the glomerular capillary wall. Serum testing revealed the presence of circulating IgG cryoglobulin. The patient was ultimately diagnosed with type 1 cryoglobulinemic glomerulonephritis.
In cases of suspected C3GN, paraffin IF is important to ensure the absence of immune complex GN. Patients with paraproteinemia or EM findings of fibrillary or microtubular substructure warrant consideration for paraffin IF to avoid misdiagnosis. This is critical to inform proper clinical management, as paraprotein-related immune complex GN warrants further evaluation for lymphoproliferative disease.