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Abstract: SA-PO665

A Curious Case of Immunoglobulin Deposition in C3-Dominant Membranoproliferative Glomerulopathy

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation


  • Nimkar, Abhishek, Northwell Health, New Hyde Park, New York, United States
  • Sharma, Purva D., Northwell Health, New Hyde Park, New York, United States

Eculizumab/Ravulizumab is a humanized murine recombinant monoclonal antibody engineered to minimize immunogenicity and proinflammatory effects by inhibiting the terminal complement component C5 to prevent the generation of the membrane attack complex. We report a case where new immunoglobulin deposits were seen on kidney biopsy in a patient with C3 glomerulopathy following use of ravulizumab.

Case Description

A 20 yo male presented with hypertension, foamy urine and hematuria. Lab work showed elevated serum creatinine of 2.9 mg/dl and elevated urine protein to creatinine ratio of 5.8 gms/gm of creatinine. Serological work showed low C3 and rest was unremarkable. Kidney biopsy was performed which showed membrano-proliferative glomerulonephritis (GN) with dominant C3 deposits. Work up for low complement mediated GN was unrevealing for atypical HUS. He received 4 doses of Ravulizumab for C3 glomerulopathy but couldn’t continue due to insurance issues. Patient initially responded to the treatment, but later serum creatinine started rising again with significant proteinuria. Patient underwent repeat kidney biopsy which revealed C3 GN with strong IgG2/4-Kappa reactivity in glomerular deposits. Patient was resumed on complement blockade and was listed for kidney transplant evaluation.


Eculizumab/Ravulizumab consists of a hybrid human IgG2 heavy chain hinge region, which does not bind Fc receptors, and the IgG4 heavy chain CH2 and CH3 regions associated with a κ light chain. The tissue deposition of IgG2, IgG4, and κ light chain has been described in literature in patients receiving this drug for C3 glomerulopathy. With the expanded use of eculizumab/ravulizumab for treatment of conditions that could benefit from terminal complement blockade, pathologists are expected to encounter more biopsy specimens with IgG2, IgG4, and κ deposits. Given its low immunogenicity and slow tissue clearance, prolonged tissue deposition of the antibody is expected, which may generate confusing results. Knowledge of this finding is important because the detection of Ig-positive monoclonal deposits in patients with clinically suspected glomerular disease could lead to misdiagnoses, especially if therapy was discontinued a while prior to the biopsy and the pathologist was not informed of antecedent eculizumab/ Ravulizumab use and if IgG subclass staining is not performed.