C3 Glomerulonephritis Associated With Unusual IgG4 Antifactor H in IgG4-related Disease

C3 glomerulonephritis (C3GN) is characterized by glomerular aggression mediated by deregulation of the alternative complement pathway. C3GN can be inherited or consequent to acquired autoantibodies, notably against factor H. We report the case of a patient with systemic active IgG4-related disease who presented for acute kidney injury with glomerular proteinuria and hypocomplementemia related to C3GN associated with IgG4-related interstitial nephritis on kidney biopsy. Factor H was low, and antifactor H IgG autoantibody was detected. Detection of other acquired or genetic complement alternative pathway disorders returned negative. After initial failure of oral corticoids and intravenous rituximab, the patient was successfully treated by intravenous cyclophosphamide followed by maintenance therapy with rituximab. Antifactor H autoantibody isotypes were IgG1 and IgG3, mainly as all antifactor H in positive controls but also IgG4, which is unusual. This suggests a link in this case between the oligoclonal expansion of plasma cells in IgG4-related disease and the production of antifactor H antibodies, especially of IgG4 isotype.