Rituximab and Fibrillary Glomerulonephritis: Interest of B Cell Reconstitution Monitoring

Abstract

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease characterized by glomerular deposition of randomly arranged non-amyloid fibrils. FGN has a poor renal prognosis and its optimal treatment is a medical challenge. Rituximab therapy has recently emerged as a promising approach even though its mechanism of action remains hypothetical. We describe the case of a 55-year-old woman with FGN successfully treated by rituximab. During the 36-month follow-up, she had three relapses of FGN, occurring each time in the context of B cell recovery. Investigation of the distribution of B cell subpopulations at the time of the third relapse showed, as previously described for some immunological diseases, an increase in the proportion of switched memory B cells relative to healthy subjects, whereas global memory B cell pool was not yet recovered. This case suggests that B cell reconstitution should be carefully monitored in the management of FGN treated with rituximab.

Keywords: B cell reconstitution; fibrillary glomerulonephritis; rituximab.

Figure 1

Representative kidney biopsy findings showing FGN. (A) Marked mesangial matrix expansion and focal thickening of glomerular basement membrane by deposits (Masson’s trichrome staining × 400); immunofluorescence: mesangial and capillary loop smudgy positivity for IgG (B) and C3 (C) (×400); (D) weak capillary wall staining for IgM (×400); (E) immunofluorescence staining for IgG subclasses revealed positive staining for IgG4 (×400); (F) electron microscopy: deposits were composed of randomly arranged non branching fibrils of 16 nm in diameter (×40,000).

Figure 2

Close temporal relationship between CD19+ cell counts and proteinuria relapse during follow-up and analysis of B cell subgroups. (A) Increased proteinuria was strongly associated with increased CD19+ cell counts after each rituximab infusion. Note that each relapse occurred approximately seven to eight months after each administration of rituximab; (B) characterization of B cell subgroups (transitional, naive, and memory B cells, and plasmablasts) according to CD24 and CD38 markers, among CD19 gated cells; (C) representative dot plots from the patient (PA) and healthy blood donors (HBD) (n = 5). The patient displayed a lower proportion of CD27+ B cells among CD19+ cells but a higher proportion of switched memory B cells (among CD19+CD27+) relative to HBD (n = 5).