FIGURE 2.

Characteristics of the 4 clusters obtained through unsupervised cluster analysis. Clusters 1 to 3 showed evidence of fluid‐phase alternative pathway activation and a high prevalence of complement gene abnormalities (mutations) and/or nephritic factors (NeFs). In clusters 1 and 2, AP activation occurs both at the C3 and C5 levels, as documented by low serum C3 and high levels of sC5b‐9. Cluster 2 is distinguished by the fact that these patients also have signs of activation of the classical pathway (Ig and C1q staining in biopsy). In cluster 3, fluid‐phase C3 convertase activity predominates over C5 convertase activity, as shown by mostly normal sC5b‐9 levels. Most of these patients have highly electron‐dense deposits in the glomerular basement membrane. Most patients in clusters 1 and 2 carried NeFs that stabilized both the C3 and the C5 convertases, whereas NeFs stabilizing the C3 convertase only were mainly found in cluster 3. Cluster 4 patients separated from the others since they have normal serum C3 levels but intense C3 staining in the kidney, indicating solid phase AP activation in the kidney. N: normal value. Green rectangles highlight abnormalities in circulating blood, and red rectangles highlight glomerular abnormalities. Reprinted from Noris M, Daina E, Remuzzi G. Membranoproliferative glomerulonephritis: no longer the same disease and may need very different treatment. Nephrol Dial Transplant. 2021 Oct 1:gfab281. doi: 10.1093/ndt/gfab281