Intraglomerular Immune Cell Infiltration and Complement 3 Deposits in Membranoproliferative Glomerulonephritis Type I: A Serial-Biopsy Study of 25 Cases

We examined chronological changes in intraglomerular immune cell infiltration in comparison to the changes in glomerular complement 3 (C3) deposits (C3-D) and serum complement levels in 25 patients with membranoproliferative glomerulonephritis (MPGN) type I. These patients were divided into the following two groups: group A (n =13), cases in which there were fewer intraglomerular C3-D at the second biopsy (2nd-Bx) than at the first biopsy (1st-Bx); and group B (n =12), those in which the amount of C3-D at the 2nd-Bx was greater than or equal to that at the 1st-Bx. At the 1st-Bx, monocytes (Mo)/macrophages (MO) and total leukocytes (TLC) were the predominant cell types in both groups, whereas T cells were less marked. At the 2nd-Bx, only group A showed a significant decrease in the number of either Mo/Mφ (P < 0.01), TLC (P < 0.01), pan-T cells (P < 0.01), or intraglomerular nuclei per glomerular crosssection ([NIN] P < 0.01). In group B, there was a positive correlation between the number of intraglomerular pan-T cells (CD3-positive cells) and Mφ (CD68-positive cells, P < 0.05 at the 1st-Bx and P < 0.01 at the 2nd-Bx), but not in group A. An improvement in light-microscopic findings and a significant decrease of urinary protein excretion (P < 0.05) at the 2nd-Bx was observed only in group A. Hypocomplementemia (hypo-C) was found in 12 of 13 cases of group A and in eight of 12 cases of group B at the 1st-Bx. Hypo-C in group A was not found at the 2nd-Bx. On the other hand, in group B, hypo-C was still observed in the eight cases and was found in one additional case at the 2ndBx. These findings show that continuous or recurrent intraglomerular mononuclear cell infiltration and persistent complement activation with intraglomerular C3 deposition are associated with therapeutic resistance, and suggest that these phenomena may be of pathogenetic significance in MPGN type I.