Complement-mediated
glomerulonephritis, which includes C3 glomerulopathy, is characterized by dominant staining of C3 with minimal or no
immunoglobulin deposits on immunofluorescence studies. We describe a new entity of
complement-mediated
glomerulonephritis that is characterized by bright C4d staining but with no or minimal C3 or
immunoglobulin deposits on immunofluorescence studies. We label this entity as C4 glomerulopathy. C4 glomerulopathy includes C4
dense deposit disease and C4
glomerulonephritis. C4
dense deposit disease is characterized by bright C4d staining and dense deposits along glomerular basement membranes. C4
glomerulonephritis is characterized by bright C4d staining and many mesangial electron-dense deposits, with or without rare intramembranous electron-dense deposits. We describe clinical features and kidney biopsy results in a short series of 3 patients to highlight these findings. All 3 patients presented with
proteinuria, and 2 patients also had
hematuria. Kidney function was preserved in 2 patients, whereas 1 patient presented with declining kidney function. Evaluation for
autoimmune disease,
infection, and
paraprotein yielded negative results in all patients.
Complement levels were normal, although 1 patient had borderline low C4 levels. Kidney biopsy showed mesangial proliferative or
membranoproliferative glomerulonephritis with bright C4d staining and absent or minimal C1q, C3, and
immunoglobulin.
Laser microdissection and mass spectrometry of glomeruli in all 3 patients showed large to moderate numbers of spectra matching C4. Furthermore, analysis of amino acid sequences showed that they were localized to the C4d portion of C4, consistent with immunofluorescence findings. Further studies are required to determine the underlying cause. In summary, we describe a novel
complement-mediated
glomerulonephritis that is characterized by bright glomerular C4d staining with minimal or absent staining for C1q, C3, and
immunoglobulin.