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.

Monitoring anti-B cell immunotherapies in autoimmune diseases: Go with the flow. A Position Paper of the Italian Society for Clinical Cell Analysis (ISCCA)

“…79 With the ever-increasing use of anti-CD20 treatments in various autoimmune disorders, attention was shifted, rather, to the repopu-lation of memory B-Cells, which can be considered as the functional reservoir of the effector mechanisms of tissue damage and a sign of impending relapse. The relative and absolute decrease of memory B-Cells, along with an increase of naïve cells, was repeatedly confirmed as a favorable laboratory sign of response in RA, 46,79,81,82 juvenile RA (83), SLE, 28,29,43,66 multiple sclerosis, 41,83,84 systemic sclerosis, 85,86 Sjögren's syndrome, 32 glomerulonephritis [87][88][89] and neuromyelitis optica spectrum disorders 59,90 as well as in allogeneic transplantation response. 91,92 The achievement of a deep and durable B-Cell depletion has been then taken as an indicator to define the effectiveness of anti-CD20 therapies.…”

DNA J homolog subfamily B member 9 and other advances in fibrillary glomerulonephritis

“…Neither pathologic findings nor eGFR at diagnoses correlated with response to rituximab. CD19þ B-cells were appropriately depleted during rituximab therapy, and reconstitution was not associated with relapse [44 & ], although other individual cases have reported a correlation between CD19þ B-cell recovery and FGN relapse [15,51,53]. Both the presence and type of B-cell reconstitution may be important when considering rituximab monitoring in patients with FGN [53,54].…”

“…CD19þ B-cells were appropriately depleted during rituximab therapy, and reconstitution was not associated with relapse [44 & ], although other individual cases have reported a correlation between CD19þ B-cell recovery and FGN relapse [15,51,53]. Both the presence and type of B-cell reconstitution may be important when considering rituximab monitoring in patients with FGN [53,54]. Taken together with data from retrospective studies, these findings provide some evidence for use of rituximab to stabilize eGFR in patients with FGN, but do not identify reliable clinical or pathologic predictors of response.…”

The ISCCA flow protocol for the monitoring of anti‐CD20 therapies in autoimmune disorders

“…After the profound B cell depletion phase induced by anti‐CD20 MoAbs, the repopulation of memory B cells and plasmablasts has been first considered as a correlate of impending relapse or resistance to treatment (Dass et al, 2008; Leandro, Edwards, & Cambridge, 2002). On the other hand, a long‐lasting depletion of memory B cells and the reappearance of naïve B cells have been taken as signs of clinical response in a number of autoimmune disorders, such as rheumatoid arthritis (RA) (Becerra, De La Torre, Leandro, & Cambridge, 2017; Calero, Nieto, & Sanz, 2010; Dass et al, 2008; Leandro et al, 2002; Md Yusof et al, 2017; Roll, Dörner, & Tony, 2008), juvenile RA (Marasco et al, 2018), systemic lupus erythematosus (SLE) (Cassia, Alberici, Gallieni, & Jayne, 2017; Reddy et al, 2013; Reddy et al, 2017; Vital et al, 2011), Multiple Sclerosis (Baker, Marta, Pryce, Giovannoni, & Schmierer, 2017; Greenfield & Hauser, 2018), systemic sclerosis (Elhai et al, 2019; Gernert, Tony, Schwaneck, Gadeholt, & Schmalzing, 2019), Sjögren's syndrome (Mariette & Criswell, 2018), Glomerulonephritis (Colucci et al, 2016; Iijima, Sako, & Nozu, 2017; Leibler et al, 2018) and neuromyelitis optica spectrum disorders (Kim, Hyun, & Kim, 2019; Lebrun et al, 2018).…”