Membranous Nephropathy After Exposure to Immune Checkpoint Inhibitors.
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ABSTRACT:
SUBMITTER: Benyahia R
PROVIDER: S-EPMC10496011 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
Publications
Membranous Nephropathy After Exposure to Immune Checkpoint Inhibitors.
Benyahia Rayane R Lazareth Helene H Flahault Adrien A Brglez Vesna V Seitz-Polski Barbara B El Fil Samy S Mazières Julien J Ribes David D Huart Antoine A Colombat Magali M Karras Alexandre A Belliere Julie J
Kidney international reports 20230608 9
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Project description:An HLA-DR3 association with membranous nephropathy (MN) was described in 1979 and additional evidence for a genetic component to MN was suggested in 1984 in reports of familial MN. In 2009, a pathogenic autoantibody was identified against the phospholipase A2 receptor 1 (PLA2R1). Here we discuss the genetic studies that have proven the association of human leucocyte antigen class II and PLA2R1 variants and disease in MN. The common variants in PLA2R1 form a haplotype that is associated with disease incidence. The combination of the variants in both genes significantly increases the risk of disease by 78.5-fold. There are important genetic ethnic differences in MN. Disease outcome is difficult to predict and attempts to correlate the genetic association to outcome have so far not been helpful in a reproducible manner. The role of genetic variants may not only extend beyond the risk of disease development, but can also help us understand the underlying molecular biology of the PLA2R1 and its resultant pathogenicity. The genetic variants identified thus far have an association with disease and could therefore become useful biomarkers to stratify disease risk, as well as possibly identifying novel drug targets in the near future.
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Project description:Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome among adults. The identification of phospholipase A2 receptor (PLA2R) as target antigen in most patients changed the management of MN dramatically, and provided a rationale for B-cell depleting agents such as rituximab. The efficacy of rituximab in inducing remission has been investigated in several studies, including 3 randomized controlled trials, in which complete and partial remission of proteinuria was achieved in approximately two-thirds of treated patients. Due to its favorable safety profile, rituximab is now considered a first-line treatment option for MN, especially in patients at moderate and high risk of deterioration in kidney function. However, questions remain about how to best use rituximab, including the optimal dosing regimen, a potential need for maintenance therapy, and assessment of long-term safety and efficacy outcomes. In this review, we provide an overview of the current literature and discuss both strengths and limitations of "the new standard."
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