Eculizumab might benefit C3 glomerulopathies mediated by dysregulation of the alternative complement pathway. Here, we report renal biopsy findings before and after
eculizumab therapy in three patients with
dense deposit disease and two with C3 GN. All pretreatment biopsies had glomerular and tubular basement membrane deposits that stained exclusively for C3 without significant Ig. After 1 year of
therapy, there was reduction in active glomerular proliferation and neutrophil infiltration in three of five patients, consistent with effective C5 blockade, which prevents production of
chemotactin C5a. One individual with mild mesangial disease had no significant change in activity or chronicity. One patient exhibited persistent activity and worsening chronicity despite
therapy. Immunofluorescence showed no significant reduction in C3 or
C5b-9, and electron microscopy revealed persistent deposits in all cases, suggesting a long t(1/2) of
C5b-9 in extracellular matrix. Normal renal biopsies stained positive for
C5b-9 in glomeruli, tubular basement membranes, and vessel walls, albeit at lower intensity than in C3 glomerulopathy. This indication of physiologic levels of
C5b-9 activation in normal kidney potentially explains the localization of deposits in patients with dysregulation of the alternative complement pathway. All post-treatment biopsies showed de novo monoclonal staining for
IgG-κ in the same distribution as C3 and
C5b-9, mimicking monoclonal Ig deposition disease (MIDD). Staining of the γ heavy chain was restricted to the
IgG2 and
IgG4 subclasses, suggesting the binding of monoclonal
eculizumab to C5 in renal tissues. The long-term effects of this apparent
drug-tissue interaction are unknown.